INSIDER INFORMATION: Opiate Prescriptions. CRAWL INSIDE YOUR DOC'S HEAD!!!

Discussion in 'Opiates & Opioids' started by Richard_smoker, Mar 21, 2006.

  1. Richard_smoker

    Richard_smoker Gold Member

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    Interested in what your psychiatrist &/or pain control doc is thinking when you tell him you're in pain?

    Perhaps you will be shocked when you read what's going through his mind. If you know what's best for yourself (pun intended), then you will read the 'suggestions' herein very carefully.

    ***DO NOT use any of the information posted here to illegally obtain opiate prescriptions! The purpose of this post is to encourage those in legitimate pain on how to talk to their physicians. This is specifically posted for those pain patients who are afraid that their doctor will accuse them of being a drug-addict if they complain.***

    Here it is. 2 back-to-back articles copied starting on pg. 1282, JOURNAL OF PALLIATIVE MEDICINE. Volume 8, Number 6, 2005.

    Is It Pain or Addiction? #68
    DAVID E. WEISSMAN, M.D.

    THE SINGLE MOST REQUESTED educational topic
    by physicians concerning pain surrounds differentiating
    the patient in pain versus the patient
    with a substance abuse disorder. The key to
    proper assessment lies in understanding (1) the
    definitions of tolerance, physical and psychological
    dependence (a.k.a. addiction), (2) the components
    of an addictions assessment and (3) the
    differential diagnosis of the symptom of “pain.”

    DEFINITIONS
    Tolerance: the need to increase a drug to achieve
    the same effect. In clinical practice, significant
    opioid tolerance is uncommon. Tolerance may be
    present in the pain patient or the patient with a
    substance abuse disorder; by itself it is not diagnostic
    of addiction.


    Physical dependence: development of a withdrawal
    syndrome when a drug is suddenly discontinued
    or an antagonist is administered. Many
    patients taking opioids long term become physically
    dependent
    ; their presence cannot be used to
    differentiate the pain patient from the patient
    with a substance abuse disorder.

    Psychological dependence (addiction): overwhelming
    involvement with the acquisition and
    use of a drug, characterized by: loss of control,
    compulsive drug use, and use despite harm. Data
    suggest that opioids used to treat pain rarely
    leads to psychological dependence. **In other words, this is BAD if you're being treated for legitimate PAIN!**

    ADDICTION (SUBSTANCE ABUSE) ASSESSMENT
    Assess for addiction in the following domains.

    Note: one positive item from the list does not establish
    a substance abuse disorder, rather, the diagnosis
    rests on a pattern of behavior that includes
    several positive findings.

    -if you do any of these, it is considered very BAD!!!
    • Loss of control of drug use (has no partially
    filled medication bottles; will not bring in bottles
    for verification);

    • Adverse life consequences—Use despite harm
    (legal, work, social, family);

    • Indications of drug-seeking behavior (reports
    lost/stolen meds, requests for high-street value
    medications);

    Drug taking reliability (frequently takes extra
    doses, does not use medications as prescribed);

    • Abuse of other drugs (current/past abuse of
    prescription or street drugs);

    • Contact with drug culture (family or friends
    with substance abuse disorder); and

    • Cooperation with treatment plan (does not follow-
    up with referrals or use of nondrug treatments).


    DIFFERENTIAL DIAGNOSIS
    The differential diagnosis for a patient reporting
    “pain” includes:
    physical causes** (broken leg, sciatica, pseudoaddiction);
    psychological (depression, anxiety, hypochondriasis, somatization disorder);
    spiritual (impending death, grief);
    substance abuse; and
    secondary gain/malingering/criminal (desire for attention, or disability benefit or financial gain).

    **Dick's Notes: You might want to remember that in the U.S., opiates and opioids are ONLY prescribed for ONE of these reasons: PHYSICAL CAUSES.** ;)

    REFERENCES
    Sees KL, Clark HW: Opioid use in the treatment of chronic pain: Assessment of addiction. J Pain Symptom Manage 1993;8:257–264.
    Palliative Care Center, Froedtert Hospital, Milwaukee, Wisconsin. Fast Facts and Concepts*FAST FACTS AND CONCEPTS 1283
    Savage SR: Addication in the treatment of pain: significance, recognition and management. J Pain Symptom Manage 1993;8:265–278.
    Eisendrath SJ: Psychiatric aspects of chronic pain. Neurology 1995;45:S26–S34.
    Passik SD, Kirsh KL, Portenoy RK: Understanding aberrant drug-taking behavior: Addiction redefined for palliative care and pain management settings. In: Berger
    AM, Portenoy RK, Weisman DE (eds): Principles and
    Practice of Supportive Oncology Updates. Philadelphia, PA: Lippincott Williams & Wilkins, 1999;2:1–12.


    MORE DICK'S NOTES: Let me preface this next article with an explanation for those who don't quite understand the purpose of this post. "Pseudoaddiction" is something that DOCTORS CAUSE by inadequately treating their patients' pain. This is a really hot topic right now in treatment. There are new laws that make it possible for physicians to prescribe large amounts of opiate meds to those who are in persistent pain and agony. Opiates have gotten a bad rap for a long, long time--since sometime around the drug revolution post-1960's. Now the medical community is trying its hardest to ensure that docs don't underprescribe people who are actually suffering. Read the following article very carefully...

    Pseudoaddiction is one of the physical reasons for an opioid need. If you were to suffer from it, then your doctor will be obliged to treat you for it.

    A word from the wise:
    if your physician is young (i.e. a resident or preferably someone who has just finished his/her residency), then they will be much more apt to know and understand this new distinction and thus they will be much more likely to remember all the newest, most current research on pain, opiates, & compassion. In fact, a patient suffering from pseudoaddiction will be an excellent way to stroke their ego's!! This diagnosis will be fresh on their young, high-spirited minds, and who knows? They will probably want to impress their friends and their nurse by diagnosing someone with this type of physical pain!

    Pseudoaddiction #69
    DAVID E. WEISSMAN, MD

    THE TERM “PSEUDOADDICTION” was first used in
    1989 to describe an iatrogenic syndrome resulting
    from poorly treated pain. The index case
    was a 17-year-old man with leukemia, pneumonia,
    and chest wall pain. The patient displayed
    behaviors (moaning, grimacing, increasing requests
    for analgesics) wrongly interpreted by the
    physicians and nurses as indicators of addiction,
    rather than of inadequately treated pain. Put simply,
    pseudoaddiction is something that we do to
    patients, through our fears and misunderstanding
    of pain, pain treatment, and addiction.


    DIAGNOSTIC FEATURES

    1. Behaviors that suggest to the health care provider
    the possibility of psychological dependence
    (addiction):

    • Moaning or other physical behaviors in which
    the patient is trying to demonstrate to the provider
    that they are in pain;

    • Clock-watching or repeated requests for medication
    prior to the prescribed interval; and

    • Pain complaints that seem “excessive” to the
    given pain stimulus;

    2. Inadequately prescribed and titrated opioid
    analgesics; typically the use of an opioid of inadequate
    potency (e.g., 50 mg of meperidine)
    and/or at an excessive dosing interval (e.g.,
    oral morphine every 6 hours as needed).

    Anytime there is a suggestion, because of escalating
    pain behaviors, that a patient taking
    opioids may be “addicted,” pseudoaddiction
    should be considered. Perform a complete pain
    assessment and review the recent analgesic
    history:


    • Is this a pain syndrome that typically responds
    to opioids? (YES! If it's some kind of physical pain!)

    • Is the current opioid dose, route and schedule
    appropriate? (Everyone's different. All docs start out small with spread-out dosing. Then they move up!)

    If so, has a reasonable attempt at dose escalation been made? (a reasonable attempt could take 10 office visits to acquire... usually they will warn someone who is about to be cut off. and even then, it might just be a test to see if you're really still hurting)

    • Is there any past medical history to suggest a
    substance abuse disorder? (NO!!! right!? if so, then you're in the wrong forum! ;) When someone is finally allowed to enter the world of chronic opiate control, many docs will threaten and then follow-through with occasional drug tests to make sure that you're really taking the drugs and also to make sure that you don't have other drugs in 'ya.)
    Complete a comprehensive substance abuse assessment if such a disorder is suspected.

    Note: pseudoaddiction improves with the provision of adequate analgesia, including opioids and often gets SOMEWHAT better with the addition of non-opiate painkillers. In contrast, addiction gets worse when opioids are administered.



    MANAGEMENT
    If you believe the current problem is pseudoaddiction,
    there are two key management steps:

    1. Establish trust—a primary issue in most
    cases is the loss of trust between the patient
    and the health care providers. The physician
    and nursing staff should meet to discuss how
    they will restore a trusting therapeutic relationship;
    outside assistance from a pain or
    palliative care service may be helpful. Plan
    to meet with the patient and openly discuss
    the events leading up to the current problem;
    engage the patient in the decision process
    about the current and future use of analgesics.

    2. Prescribe opioids at pharmacologically appropriate
    doses and schedules; aggressively dose escalate until analgesia is achieved or toxicities develop (see Fast Facts 18, 20, 36). Frequently reevaluate progress in pain
    management and ask for consultation assistance.


    REFERENCES
    Weissman DE, Haddox JD: Opioid pseudoaddiction. Pain
    1989;36:363–366.
    Sees KL, Clark HW: Opioid use in the treatment of chronic pain: Assessment of addiction. J Pain Symptom Manage 1993;8:257–264.

    :p Hope everyone enjoyed this read!! -Dick
     
    Last edited by a moderator: Sep 10, 2017
    1. 3/5,
      For someone with chronic pain I found it very interesting to read. Thanks a ton
      Jun 15, 2014
    2. 3/5,
      Explains a lot of things and can possibly help my situation, good job!
      Apr 16, 2014
    3. 3/5,
      Important info, thank you.
      Feb 2, 2014
    4. 3/5,
      This is a very informative post, information that should be read by all intending on the merry go round of pain versus opiates. Good One
      Apr 24, 2013
    5. 5/5,
      Extremely useful and insightful information.Very well researched.
      Apr 13, 2013
    6. 3/5,
      Very good reading material!
      Apr 1, 2013
    7. 4/5,
      extremely informative, very helpful, excellent examples
      Feb 24, 2013
    8. 3/5,
      very useful info
      Oct 9, 2012
    9. 3/5,
      Awesome post. Definitely a thumbs up.
      Jan 6, 2010
    10. 4/5,
      fabulous post! great articles & insight - thank you for sharing!
      Oct 12, 2009
    11. 5/5,
      well organized and succint, well researched, a fine piece of work.
      Apr 16, 2009
    12. 4/5,
      Spectacular! Power to the patient!
      Mar 29, 2009
    13. 3/5,
      Great post on opiate Rx.
      Sep 14, 2008
    14. 3/5,
      The straight dope from smoker..xlnt
      Sep 3, 2008
    15. 4/5,
      awesome piece of info right there!!!
      Apr 5, 2008
    16. 3/5,
      Great Post's
      Jan 3, 2008
    17. 3/5,
      Great post!
      Apr 22, 2007
    18. 4/5,
      Excellent post!
      Jun 26, 2006
    19. 4/5,
      Great post, although Im 100% against using docs as drug dealers
      Apr 4, 2006
    20. 3/5,
      Great. Informative and well thought out.
      Mar 21, 2006
  2. MrJim

    MrJim Gold Member

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    Great post, man. As far as physical causes go, where do you think the tylenol ends and the opioids begin? It often varies from physician to physician, but some things such as a ruptured disc is pretty much an automatic opioid presciption. It seems if there isn't documentable physical problems doctors may be more reluctant to prescibe.
     
  3. Forthesevenlakes

    Forthesevenlakes Platinum Member

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    so true, and even then, depending on the doctor, they may get pretty stingy with the opiates. I have seen friends get prescribed laughable amounts of 4-6 5 mg hydrocodone when they had respiratory infections so bad that they couldnt sleep, and barely speak, as if somehow bronchitis magically dissapates over 24 hours and GOD FORBID these patients have any medication leftover when that happens! Excellent post as always.
     
  4. Richard_smoker

    Richard_smoker Gold Member

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    The question about where tylenol ends and opiates begin is difficult to answer, but here are some really great suggestions:

    1. Most important is physician's attitude. Find a good one. Preferrably one that has been recommended for previous generosity and/or being sensitive to pain patients. Always be friendly, establish good rapport, etc. on your 1st visit. Maybe you can even bring him/her some extra brownies that you made for your kid's school teacher on the 2nd or 3rd visit.

    2. Don't ask for what you want by name! they like to make the decisions, so let them do it.

    3. Don't EVER act like you're upset with what they give you (until you eagerly go home and try it)... Even if you know they're ripping you off with a script for something shitty, you need to act kinda-sorta excited and ask something like this: "So this will make me feel normal again!?? THANKS DOC!!"

    4. If you didn't get relief, then call the office back within a few days or a week and schedule another appointment asap. You'll be surprised how fast most physicians can pick up on drug-seekers, so don't say things like "never" or "ever" or "always." When they ask how the tylenol or advil or whatever they gave you worked, be sure and give it a little bit of credit. Tell them that you definitely noticed some relief, but you're still uncomfortable.

    4. Don't ever EVER act like you know ANYTHING about medicine, medical conditions, or anything like that. Remember to lube the gears. No squeaky wheels-->i.e. pretend you're ignorant and that he's the smartest person in the world.

    5. Try and smile thru the pain... In other words, while you're grunting, etc... Be sure and apologize for everything you do so he'll feel like the last thing in the world you would ever do is put him out or waste his time.

    6. Be patient... (after all, that's what you are--one of your new doc's PATIENTS!) -sorry for the stupid pun.

    7... REMEMBER: YOU'RE EXCITED TO BE ABLE TO TRY OUT ANYTHING THAT MIGHT HELP--INCLUDING ANTI-DEPRESSANTS!!! :) After the recent bullshit that went down in FL over o.c.'s, I wouldn't be surprised to see drs who start requiring documentation of all other drugs having been tried. Just wait and you will eventually exaust all medical possibilities...

    and when you're beginning to get impatient, just remember that 2 of the top 6 most commonly prescribed pills in the USA last year were 2 different brands of generic hydrocodone. ;)

    gotta run, but if I think of some more, I will post them later. If anyone knows something to add, feel free.

    --To Pain-Free Existences! :) -RS
     
    1. 4/5,
      Good info. And funny too.
      Aug 25, 2009
    2. 3/5,
      very informational! this guy knows his stuff!
      Sep 21, 2008
    3. 4/5,
      Providing Good thoughts and a good thread
      Oct 9, 2007
    4. 4/5,
      great post as usual
      Mar 31, 2006
  5. Pinkavvy

    Pinkavvy Platinum Member & Advisor

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    Richard - excellent post! I'm pretty sure I posted a guide to getting prescribed opiates on here somewhere as well. Great minds Must think alike. ;)
     
  6. Nagognog2

    Nagognog2 Iridium Member

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    I met a street junkie who had a sure-fire way of getting opiates prescribed: He jumped in front of moving cars and got his leg broken. He did this many times.

    One day he jumped out in front of a speeding mail truck. He didn't need any opiates after that.
     
    1. 3/5,
      not relevant.
      Mar 29, 2009
  7. Alicia

    Alicia Gold Member

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    from earth
    Euuuuuu that could defiantly stain
     
  8. junglistNside

    junglistNside Newbie

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    having a history doesnt always work against you. for instance swim cut off some fingers at work recently. The Dr knew they had a history, and for this reason prescribed elevated amounts of dilaudid. Knowing standard dosage would not be effective. Just thought Id add that.
     
  9. r-evolution

    r-evolution Newbie

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    just dont tell them that you have psychological pain. even though scientifically, this kind of pain behaves almost like physical pain and responds just as well to treatment with opioids, well thats just sumpin else. like a mental disease is just not a "real" disease.
    all in all, it could just be that some day they will find the holy grail, that mental pain IS equivalent to physical one and "pseudoaddiction" is just the physical equivalent to "addiction" psychologically.
    but as long as there is the reigning middle class of puritans who like to forbid everything that could be pleasurable, e.g. sinful, "that just won't play, sam"
     
  10. kritikal

    kritikal Silver Member

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    It seems that doctors really do not want to prescribe something because of the addiction potential towards it.

    I was prescribed Oxycodone at a hospital. I went to the doctors told him i was still in a great amount of pain and the Med was only taking the edge off. He said because it can lead to Habituation that he wanted to take me off it and gave me tylenol 3. The pain got much greater and i suggested that that has been the only thing to help and i dont care what you give me just get rid of this pain. He gave me temazepam to sleep and Suggested ?ASPIRIN? of course this did jack shit so he gave me Diazepam and Propoxyphene.

    You cant get into a doctors head no matter what you do. I can only suggest you say that you want the thing that will make you least "drowsy" get rid of the pain the best and you just want to get on with your life. (Although this still probably wont work.)

    Well the best way to get prescribed Opiates would be to go into the doctors room. Knock him out, Jump on his computer, Make up a script for what you want with XXXXX repeats. And run out of the clinic Laughing.
     
  11. Forthesevenlakes

    Forthesevenlakes Platinum Member

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    Or you could go to a pain relief specialist if your area has any, they generally are more accomodating to people with diagnosed chronic pain. If that fails I think kritikal's last paragraph in the previous post might be the only other option, somehow I feel that getting some H on the street for chronic pain might be a little extreme.
     
  12. Richard_smoker

    Richard_smoker Gold Member

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    Actually, I once bought an entire little book entitled, "The Psychiatrists Handbook for Chronic Pain Management."

    It's all about prescribing opiates for psychiatric pain. But don't let the name mislead you. There are all types of pain that falls into this category. Off the top of my head, there are somatizers, somatiform disorders, malingering, and something else that I can't remember.

    But somatiform disorder is very real pain and it is, paradoxically also, very imagined. You see, depending upon cultures and things like that, different people will actually choose to actually "feel" their anxiety, frustrations, depression, and foul moods (consciously or not--in the case of somatiform d/o, it is unconscious).

    Here are 2 examples:

    1. An elderly man with suicidal depression. The last thing a "strong" MANLY man from the depression-era will ever admit to is something mentally wrong like depression, chronic sadness, or any kind of mental disorder. So, in his case, he will describe every other symptom under the sun BUT being depressed.

    2. Women. (seriously! not trying to be funny here). Women, often sexually abused early in life. These patients will often somatize their psychological discomfort into their abdominal region. Usually present with long, extensive histories suggestive of endometriosis, repeat surgeries of GI tract (gallbladder, adhesion lysis, etc), and surgeries of female parts (endometrial exploration/lysis, hysterectomy,etc.), but none of these 'treatments' work to heal the abdominal pain. why? because the pain is originating in the brain, then traveling down to the nether-regions, and back up again where it is sensed as an "OUCH! MOTHER FUCKER!" sensation.

    -not really! i don't think anyone knows the real explanation for the abdominal pain link. Just that it's more common in women and more common still in those who were raped as kids. these people are very UNlikely to get narcotics unless they go to a VERY kind physician.
    In these cases, the pain is very VERY real. don't confuse central-neurologic-in-origin with imagined. Because there is something inherently WRONG with the way that nerve signals are being transmitted in terms of pain signals, it is believed to be why drugs that are traditionally used for their anti-depressant effect are effective in stabilizing these pains. The drugs stabilize faulty, negatively perceived nerve firing in depressed people and they also appear to do the same thing in chronic pain patients... thus, fixing their problems.

    Of course, if you were a BAD, EVIL drug-seeker and trying to manipulate your physician into giving you narcotics, then you would probably tell him that even after 4-6 weeks of taking your anti-depressant RELIGIOUSLY, you still don't really notice any improvement in your pain... but maybe you could say, "But I've noticed that I'm a lot more cheerful lately! I mean, it's impossible to smile when this summbitch starts flaring up, but I guess if I had to be totally honest and descriptive, I think my spirits are elevated a little bit, and I might be sleeping a litttle bit better, but NO... it hasn't done shit to help the pain. What other options do we have for treating this damn pain?"

    ***thought for the day***
    Think about this for a while... Pain.
    What is Pain?
    • Pain is what keeps doctors in business...
    • If it weren't for pain, there might not ever have been a need for a physician...
    • If it weren't for pain now, docs might be just like lawyers. a dime a dozen and struggling to make ends meet. (just kidding by the way--all you lawyers out there!)
    • Pain.
    • A doctor's best friend.
    • The bane of his existence.
    • Does the doctor HATE pain patients???
    • OR does he ABSOLUTELY NEED THEM AND THRIVE OFF THEIR VERY EXISTENCE??
    • Also, consider the 'difficult' pain patients--the ones who he eventually must place on heavy-hitting, high-dosage narcotics... What does he think of THEM? You know, not the ones who walk in the door asking for lortabs... the OTHER ones. the ones that started out begging him for help with something that is essentially inoperable and untreatable?? Wouldn't it be pretty normal, in fact, for him to feel a giant burst of EGO-juice flowing when he finally found a drug and doseage strong enough to stamp out your never-ending, life-destroying frustration, agony, & PAIN!?
    • You be the judge. -RS
     
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  13. Forthesevenlakes

    Forthesevenlakes Platinum Member

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    Ah, the somatoform disorders. I havent considered them in some time, I didn't think they were very common in western culture, anymore, but certainly psychiatric pain can be perceived as real pain. I know people who actually do have to be treated with narcotics for pain that actually comes from their nerves, but that was triggered by specific events, and that the people perceive as physical organ pain (yet their organs are completely fine).
     
  14. Richard_smoker

    Richard_smoker Gold Member

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    Here's something very relevant. Study it carefully. There are more on the way. This comes from a frequently updated 'guide' for physicians to stay up-to-date.

    Definition, pathogenesis, and evaluation of chronic pain

    Zahid H Bajwa, MD, Carol A Warfield, MD

    The literature review is current through December 2005; this topic was last changed on September 2, 2005.

    INTRODUCTION — Historically chronic pain has been undertreated or ignored altogether in the clinical arena, despite great interest in the study of pain from both psychological and physical frames of reference. Many afflicted patients come to believe that pain is something they must endure, although suicide has often been used as a way out of severe chronic pain and disability.
    Our knowledge about pain is largely rooted in benchmark studies, such as Melzack and Wall's gate control theory introduced in 1965 [1], which predate the relatively recent organization of pain management into a medical subspecialty. Research aimed at understanding pain, from the molecular biology of nociceptive pathways to the psychosocial interplay that influences the human experience of pain, has led to the development and application of treatment strategies that are positively impacting the lives of people living with chronic pain.

    An overview of the definition, classification, pathogenesis, and evaluation of chronic pain is presented here. General therapeutic principles are discussed separately. Specific disorders are discussed in more detail elsewhere.

    DEFINITION AND CLASSIFICATION
    — Acute pain is a vital, protective mechanism that permits us to live in an environment fraught with potential dangers [2]. Its importance is most clearly illustrated in the rare cases of congenital absence of nociceptors in which babies and children are prone to self mutilation and continuous environmental injuries, usually resulting in death at a very young age.

    In contrast, chronic pain serves no such physiologic role and is itself not a symptom, but a disease state. It is usually defined as pain which lasts beyond the ordinary duration of time that an insult or injury to the body needs to heal. This is commonly thought of as four to six weeks, although others have chosen three months as the dividing line between acute and chronic pain [3]. The difference is more than semantic; pain that outlasts this period may be a harbinger of a serious condition, such as Complex Regional Pain Syndrome (CRPS), in which treatment delay may lead to an irreversible and intractable condition.

    Classification — A taxonomy of pain has been very difficult to derive for many reasons, not the least of which is the presence of pain as a feature in so many disease states. This coupled with the subjective nature of pain as a symptom, and the wide variety of practitioners and opinions within the field of pain management, has made standardization of pain taxonomy imprecise and complicated.

    The International Society for the Study of Pain (IASP) established a committee in the 1980s to attempt the arduous task of a chronic pain classification [4]. They defined pain as "an unpleasant sensory and emotional experience," and devised a scheme that codes pain disorders along the following five axes: region involved; systems involved; temporal characteristics; degree of intensity; time since onset; and etiology.

    Simpler diagnostic schemes are used durig the day to day practice of pain medicine for the purpose of directing treatment.

    Nociceptive pain
    — Nociceptive pain is the perception of nociceptive input described in terms of tissue damage (eg, postoperative pain). Nociceptive pain is further subdivided into somatic and visceral pain.

    ·Somatic pain arises from damage to body tissues. It is well localized but variable in description and experience.

    ·Visceral pain is pain arising from the viscera mediated by stretch receptors. It is poorly localized, deep, dull, and cramping (eg, appendicitis, cholecystitis, pleurisy).

    Neuropathic pain
    — Neuropathic pain is pain arising from abnormal neural activity secondary to disease or injury of the nervous system. It remains persistent without ongoing disease (eg, diabetic neuropathy, trigeminal neuralgia, or thalamic pain syndrome).

    Neuropathic pain is further subdivided into the following:

    ·Sympathetically mediated pain is pain arising from a peripheral nerve lesion and associated with autonomic changes (eg, complex regional pain syndrome I and II [reflex sympathetic dystrophy and causalgia]).

    ·Nonsympathetically mediated pain is due to damage to a peripheral nerve without autonomic change (eg, post-herpetic neuralgia, neuroma formation).

    ·Central pain arises from abnormal central nervous system (CNS) activity (eg, phantom limb pain, pain from spinal cord injuries, and post-stroke pain).

    SCOPE OF THE PROBLEM — The impact of acute and chronic pain on our society is staggering. As one author states, "Throughout the world, chronic pain is the most frequent cause of suffering and disability that seriously impair the quality of life" [3]. A National Institutes of Health publication states that chronic pain is the third largest health problem in the world, affecting 65 million Americans in 1982 [5]. A cross-sectional study in a county in Sweden in 1999 found prevalences of current and chronic pain of 49 and 54 percent, respectively [6].
    Pain-related problems account for up to 80 percent of visits to physicians; the price tag for back pain alone is estimated to be $30 to 50 billion annually in the United States [7]. Other estimates, taking into account lost wages and social support, suggest that the cost to taxpayers of chronic pain is between $15,000 and $24,000 per patient per year [8].

    NEURAL BASIS OF PAIN
    — Pain begins in the periphery through the specialized nociceptors that are the nerve terminals of the primary afferent fibers. They are categorized by the kind of stimulation they respond to and the nature of their response.

    ·Myelinated nociceptors are relatively fast conducting A-delta fibers. Some respond readily to heat, the mechanothermal receptors (MTRs); others are high threshold mechanoreceptors (HTMs). The discharge intensity is linearly related to the degree of the stimulus [9].

    ·Unmyelinated C fibers constitute the large majority of peripheral nociceptors. Most are classified as C-polymodal nociceptors (C-PMN), responding to thermal, mechanical, and chemical stimuli (and to itch). These are slow conducting primary afferents with receptive fields that are smaller than those of A-delta nociceptors.

    Nociceptors also vary in their threshold to response and their rate of firing to the dorsal horn, allowing afferent signals to encode into the CNS for processing. Wide Dynamic Range (WDR) nociceptors respond to a continuum of stimuli such as warmth up through the noxious range of temperatures. Other nociceptors are specific for a noxious stimulus and are called Nociceptor Specific (NS).

    Each of these nociceptors contributes to the pain experience somewhat differently. A fibers are responsible for the first (immediate) sharp pain; the delayed pain, characterized as dull, is mediated by C fibers. The average noxious stimulus will affect most or all primary afferent nociceptors in various combinations, and they will sum to produce the subjective experience.

    Nociception at the level of the head is carried via the cell bodies in the sensory ganglia of cranial nerves V, VII, IX, and X. Below this level, noxious stimuli are carried via the primary afferents to the spinal cord. These first-order neurons have their cell bodies in the dorsal root ganglion (DRG). In the case of the visceral afferents, the fibers travel with sympathetic and parasympathetic fibers.
    Primary afferents first access the spinal cord through Lissauer's tract where they may ascend or descend one or two spinal levels prior to synapsing with second-order neurons in the dorsal horn. Gray matter in the dorsal horn is divided histologically into 10 layers, Rexed's laminae, of which the first two laminae (I, the marginal zone and II, the substantia gelatinosa) are the primary targets for the terminals of the nociceptive primary afferents. Levels III and IV may play an inhibitory role. Rostrally projecting second order neurons emerge largely out of laminae I, II, V, VII, and VIII; lamina V cells in particular have a wide dynamic range, receiving input from both nociceptive and non-nociceptive afferents, and demonstrate a greater degree of convergence. It is believed that the deep layers receive input from muscles and viscera [9]. Within Rexed's laminae exist many interneurons. These are thought to provide a mechanism that permits "cross-talk" between the various layers and may alter the impulses that ultimately ascend into higher centers.

    The spinothalamic tract, located within the anterolateral quadrant of the spinal cord, is the primary ascending pathway of nociceptive information. This tract ascends through the brainstem and into the thalamus, which acts as a relay distributing nociceptive information to cortical and extracortical targets. The spinothalamic tract ultimately gives rise to two distinct pathways, the lateral pathway, projecting to the somatosensory cortex to subserve the sensory-discriminative aspect of pain, and the paramedian pathways, projecting to widespread cortical areas, including frontal lobes, which process the affective-motivational aspects of pain. Several other ascending tracts (the spinohypothalamic, the spinoreticular, and the spinopontoamygdala tracts) are likely to be involved in other aspects of nociception, such as sleep perturbation and the arousal and emotional aspects of pain.

    Pain from the face and head is carried by cranial nerves V, VII, IX, X, and from the posterior division of the upper cervical nerves. The cranial primary afferents synapse in the trigeminal system which consists of the three sensory nuclei. As in the spinothalamic tract, fibers from the trigeminal system ascend to the thalamus and other targets.

    The CNS is equipped with a descending or modulatory system by which afferent nociceptive information may be altered. Several regions of the brain are involved in this activity, including the somatosensory cortex, the hypothalamus, the periaquaductal gray, and areas in the pons including the lateral tegmental area and the raphe magnus. Stimulation of these areas causes analgesia. These structures send fibers through the dorsolateral funiculus to laminae I and V in the dorsal horn of the spinal cord. Three endogenous systems are involved in the descending control of nociceptive information: the opioid system; the noradrenergic system; and the serotonergic system.

    EVALUATION — The nature of taking a history and the physical and diagnostic work-up of patients with chronic pain will depend upon the patients' presenting complaints. However, certain aspects are similar regardless of the presentation.

    History — As with any medical work-up, the physician begins with a thorough history of the present illness. Several questions can focus the evaluation.

    How did the pain begin? — A good starting point is to ask the patient to describe how the pain began. Was there a precipitating event, such as trauma or surgery, or did it begin spontaneously in an acute or gradual fashion?

    With trauma, it is important to get the details of the injury. With a motor vehicle accident (MVA), for example, it is important to know how the vehicles collided, what restraint systems were used, the speed of the collision, the degree of damage to the vehicle, and so on. In addition, it is important to determine the disposition of the patient following the trauma. Did he or she go to an emergency unit and, if so, what did the work-up reveal? Was the patient admitted to the hospital? What treatment did the patient receive? These types of questions allow the physician to determine if the degree of trauma is commensurate with the presentation; mild trauma that is associated with a dramatic presentation may suggest embellishment of symptoms for secondary gain.

    Physicians must keep in mind that the response to pain varies greatly from one individual to another, as well as between cultures. Find out if the injury was work related and, if so, whether the patient is collecting worker's compensation or disability or if the patient is currently in litigation. Answers to these questions may have prognostic relevance.

    How is the pain described? — Allow the patient to verbalize the painful symptoms. What is the location of the pain? Is it focal, such as frontal headache, or does it exist in various locations that are discrete or contiguous, such as lumbar radiculopathy? Does the pain seem to have a point of emanation and, if so, where does it go?
    Inquire specifically about the depth of the pain. Is it superficial and easy to localize as in somatic pain, or does it seem to come from deep within the body over a more generalized region, the way visceral pain presents?
    It is important to allow the patient to describe the pain using his or her own words. Studies evaluating the adjectives that people use have revealed two broad categories of descriptors that fall into either sensory or affective groups [9]. In the former, words such as sharp, dull, and cramping were noted to communicate a definite sensation in a particular part of the body, as opposed to descriptive terms such as dreadful, vicious, and cruel, which connote a more emotional component to the patient's pain experience. Uncovering and assisting the patient with such negative feelings can be an important part of therapy.

    The other relevant issue surrounding the patient's description of pain is that the particular words chosen may be an important clue to the underlying etiology. As an example, radiculopathy produces "sharp" and "shooting" pain or "numbness" and "tingling."

    What is the intensity of pain?
    — Query the patient about the intensity of pain. Although there is no quantitative biochemical or neurophysiologic test for pain, tools have been devised to assess pain intensity. The verbal numerical scale, rating pain from zero for "no pain," to 10 for "the worst imaginable pain" is easily implemented and recorded during frequent assessments. Similarly, a 100-centimeter visual analog scale may be used, with or without intensity descriptors (show figure 1). These instruments are useful for tracking pain intensity, but unidimensional in that they do not reflect the complexity of the pain experience.

    A visual analog pain score for one patient may not mean the same thing to another, but it is reliable on repeated use in the same patient [10], allowing serial assessments by different clinicians over the course of treatment. Pain scores should be recorded, like the vital signs [11], with intervention performed when the score exceeds an acceptable level.

    More sophisticated testing is also available in forms such as the McGill Pain Questionnaire (MPQ), which is frequently used in pain management centers [12]. The patient chooses among 16 groups of descriptive words to characterize the sensory, affective, and evaluative qualities of his pain. Four additional word groups are specific to certain pain conditions. A pain intensity scale, a questionnaire on the use of analgesics and prior pain experience, and a human figure drawing on which the patient indicates his pain location are also included in the MPQ. The disadvantage of the MPQ is that it is not self-administered, and takes up to 20 minutes to complete.

    What improves the pain? — Questioning patients about factors that improve their pain, as well as its temporal characteristics, may prove helpful in directing the treatment. Does it exhibit a periodicity, and how long does it last?

    Determine what other types of therapy the patient has tried and what benefit, if any, they had. Inquire specifically about surgery, medications, physical therapy, chiropractic, biobehavioral, and complementary methods.

    Is there anything important in the past medical history?
    — Be on the lookout for serious medical conditions in the patient's history that may present with pain. Myocardial ischemia, neoplasm, and an expanding aortic aneurysm masquerading as back pain are examples. Also seek out concurrent medical conditions that may be associated with pain symptoms, such as diabetic neuropathy, AIDS, and peripheral vascular disease leading to claudication.

    Ask about past psychological history, particularly with regard to depression, anxiety, and post-traumatic stress disorder. The presence of coexisting psychopathology may add complexity to the treatment of chronic pain, particularly with drug and alcohol addiction and depression, but should in no way lead the physician away from seeking a primary chronic pain diagnosis.

    How does the pain impact the patient's life?
    — It is important to know how the symptoms have impacted the patient's life at home, with friends, and at work. Does the patient have a support structure in place, and has he or she been able to adapt to the disability and psychological stress that comes with chronic pain? What activities is the patient able or unable to perform? Is the pain preventing the patient from caring for a child, working, or performing basic activities of daily living? Patients with pain that is severe and/or long-standing are vulnerable to psychological dysfunction such as depression, anxiety, and mood disorders. The physician must determine whether progress can be made in the absence of therapy that is directed toward the psychosocial component of the pain syndrome.

    What previous evaluations have occurred?
    — Ascertain the results of previous evaluations. Many chronic pain patients, particularly with longstanding disease, will come with voluminous records and multiple diagnostic studies; others will have difficulty remembering where previous evaluations were performed. In either case, much of the work-up may have already been done, obviating the need for additional tests. Particularly for chronic disease that spans many years, previously obtained records can be used later to help piece together a clearer understanding of the problem. On the other hand, avoid reading previous evaluations and establishing a bias prior to meeting with the patient.

    Physical examination
    — The physical examination of patients with chronic pain begins by ushering them from the waiting area into the examination room. Watch these patients closely. Observe them rising from the waiting room chair. Do they stand up straight away, or do they push off with their arms, twisting and turning up into a stooped posture? Observe their gait as they walk to the examining room. It is antalgic? Do they compensate for a bad leg or back by altering their gait, and is this motion placing other structures at risk for strain or injury? Observe pain behaviors throughout the examination, such as facial grimacing, verbalization of pain, and affect. Pain behavior may represent severe discomfort with walking or moving through certain positions; however, it can also be a telltale sign of malingering or simply an attempt by the patient to convey (in an exaggerated way) that he or she has been suffering. On the other hand, a patient with a long course of chronic pain may feel that the physician needs convincing that the problem is worthy of his or her time, and embellishment is neither unusual nor an indication that the pain does not exist.
    Note general appearances, dress, and hygiene. Note splinting and compensatory movements that patients in pain will use to protect a painful region of the body. Is this activity consistent throughout the examination?
    A full physical examination should be performed regardless of the patient's complaint; this includes a complete neurologic examination. Important findings can be missed by focusing the examination only in the area of the patient's symptoms.

    OBSTACLES TO EFFECTIVE TREATMENT
    — Treatment of chronic pain is largely unavailable in many parts of the world. In the United States and many other developed nations, where there is wide availability of effective drugs, techniques, and adjunctive therapies, many people still continue to receive inadequate treatment or no treatment at all and are living with varying degrees of pain and its accompanying anguish, despair, and depression. Some of these patients, particularly the older population, have resigned themselves to living with their pain or, in the presence of coexisting medical problems, patients believe (or have been advised) that treatment is too risky. Other patients are turned away from medical care when their treatments fail.

    The case of a patient with failed back syndrome illustrates these problems. After one or more surgeries, the patient still has pain despite the fact that there is no longer any surgically remediable pathology. The problem may be partially one of CNS plasticity (the development of altered nociceptive pathways in the spinal cord and higher centers) but, as far as the patient is concerned, the pain is still present, perhaps worse than before, and frustration gradually sets in. The patient may believe that the surgery was not performed properly and seeks out other surgical opinions. In time the patient continues to collect varying opinions, diagnostic work-ups, and medications and therapies, some of which may provide moderate but short-lived relief. Nevertheless, the pain persists and ultimately wears down the patient's coping mechanisms. An increasingly frustrated, perhaps angry or depressed patient now presents to the primary care physician or other specialist with numerous records and diagnostic studies in hand.

    Such patients may be viewed as confrontational, hostile, or as having primary psychological problems, and may be labeled as a "drug seeker" or malingerer, particularly if opioids have been prescribed for pain management. It is at this juncture that many physicians will bow out, not wanting to get involved with a patient they do not feel they can help or sensing a tendency toward litigation from the patient who speaks pejoratively about the care rendered thus far. Another test is ordered, a medication is prescribed, and the patient is referred elsewhere, thereby perpetuating the vicious circle.

    There are a number of potential barriers to helping these patients. Two major ones include the presence of psychiatric comorbidity and a fear of untoward effects of pain medications.

    Psychiatric comorbidity
    — A significant portion of patients presenting with chronic pain also have histories of primary psychiatric comorbidity. It is important to distinguish them from patients who are developing secondary psychological problems, that is, patients who are developing symptoms of anxiety, depression, or other expressions of psychopathology in reaction to their pain.
    Nociceptive pathways are modulated by psychological processes, which probably play an important role in amplifying pain symptomatology [13]. Some patients with significant psychopathology who are adequately treated by their psychiatrists present with a straightforward diagnosis such as lumbar radiculopathy and respond promptly to treatment of an essentially organic problem. Conversely, depression, anxiety, post-traumatic stress disorder, substance abuse, and other psychiatric disorders can present formidable obstacles to diagnosing and treating many pain syndromes; in some cases they may be largely responsible for the patient's presenting symptoms. For this reason, patients with longstanding or complex pain problems should be treated with a multidisciplinary approach that includes an evaluation and close collaboration by a mental health professional who can diagnose and treat this aspect of the dysfunction. With the exception of malingering and factitious disorder, pain should be regarded as genuine. In any case, the inclusion of Axis I and/or II diagnoses in the patient's history should never provide the grounds to dismiss the patient's complaints of pain.

    Patients who live with chronic pain frequently speak of how the pain has taken its toll emotionally. Such stories tend to reflect the patient's psychological state, as well as the way chronic pain has affected his or her relationships with loved ones, friends, and potentially his or her employer. Besides living with pain, the patient may feel angry, isolated, and helpless, and is often afraid that he or she has lost the ability to engage in productive employment and earn a living, or be a good spouse, parent, lover, or friend. Depression and anxiety are two of the most common psychological correlates of chronic pain and greatly complicate the patient's conditions and treatment [14]. Sleep disturbance, loss of appetite, lack of energy, and diminished physical activity all contribute to an increasingly debilitated state and amplify the patient's pain symptoms. Patients commonly describe a lack of pleasure and an absence of control in their lives; ultimately, as they continue to seek assistance in desperation, they become increasingly vulnerable to treatments that may be highly suspect or even dangerous.

    A number of instruments or psychological tests are widely employed to screen the psychological profiles of chronic pain patients. Two that are in common use are the Beck Depression Inventory and the Minnesota Multiphasic Personality Inventory II (MMPI-2). The former is a brief, 21-item, self-reporting questionnaire that assesses the degree to which depressive symptomatology is present. The latter is an extensive true/false questionnaire consisting of more than 500 items factored across 10 clinical scales, as well as a variety of validity, secondary, and experimental scales. The MMPI-2 has been used extensively to verify clinical impressions about the psychological aspects of a patient's chronic pain and to predict responses to medical and surgical pain treatments [15-17].
    In some cases patients give up altogether, spiraling further into depression and despair. Success in treating these individuals is predicated upon first winning back their trust and confidence. This involves listening to them, believing them, and making a commitment to try to help. In our experience, very few patients are seeking "magic bullets" or instant cures. Instead, most are satisfied with the knowledge that their physicians will make an honest effort to help them in a gradual and stepwise fashion. Where psychological evaluations and/or adjunctive therapies are indicated, patients can be very accepting as long as thorough explanation of the purpose and goals of their treatment is provided. Not doing so may threaten patients' trust and undermine the doctor-patient relationship.

    Untoward effects of pain medications
    — Another issue that stands in the way of effective treatment of pain is the fear of untoward effects of pain medications. In the case of opioids, addiction, cognitive deficits, and respiratory depression continue to be the primary areas of concern for medical personnel. Many patients also fear becoming addicted or experiencing the sedation, nausea, or constipation frequently associated with opioids. For patients with malignant pain, the need for potent opioid pain medications is synonymous with advancement of disease; it is not unusual to see patients in this situation minimizing their symptoms to avoid having to accept such a difficult reality.

    Other pain medications have alternate adverse effects. Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly associated with gastropathy, renal disease, and coagulopathy. For other classes of medication, such as tricyclic antidepressants, anticonvulsants, and alpha-2 agents, there often is a misunderstanding between the patient and the physician about the role of the medication for pain management.

    REFERRAL TO PAIN SPECIALISTS
    — Although pain is one of the most common presenting symptoms to the primary care physician, only a small percentage of patients ultimately are seen by a physician specializing in pain medicine. The majority of these individuals are referred for one of the following chronic pain problems:

    ·Low back pain (eg, lumbar radiculopathy, spinal stenosis, facet syndrome, myofascial pain)
    ·Neck/Shoulder pain (eg, whiplash, cervical radiculopathy, fibromyalgia)
    ·Headache (eg, migraine, cluster, tension type, cervicogenic)
    ·Musculoskeletal pain (eg, soft tissue injury, myofascial pain syndrome, fibromyalgia, arthritis)
    ·Neuropathic pain (eg, post-herpetic neuralgia, chronic regional pain syndrome I and II, phantom limb pain, diabetic neuropathy)
    ·Chronic postoperative pain (eg, post-thoracotomy pain, neuroma formation, neuropraxia)
    ·Cancer pain (eg, post-radiation plexopathies, bony pain secondary to metastases, visceral pain from expanding masses)

    In many cases, patients are referred to a pain specialist because their symptoms are debilitating, are located at multiple sites, and/or do not respond to first line therapy. Most pain specialists agree, however, that referrals are frequently made too late when patients are beyond "the golden hour." This is especially true of neuropathic forms of pain and cancer pain. When to refer to a pain specialist remains a controversial question; referral should certainly occur by the time significant disability or loss of functioning are observed or when pain behaviors have coalesced or maladaptive coping strategies have emerged. Early referral is generally warranted for patients suffering from complex regional pain syndrome I and II since aggressive intervention is more likely to be effective early in the course of the disease.

    REFERENCES
    1. Melzack, R, Wall, PD. Pain mechanisms: A new theory. Science 1965; 150:971.
    2. Woolf, CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 2004; 140:441.
    3. Bonica, JJ. The management of pain. In: Lea and Febiger, 2nd ed, Philadelphia 1990.
    4. Mersky, H. Classification of chronic pain: Description of chronic pain syndromes and definition of pain terms. Pain 1986; S1(3).
    5. National Institutes of Health. Chronic pain: Hope through research. Bethesda, MD, Publication no. 82-2406, 1982.
    6. Gerdle, B, Bjork, J, Henriksson, C, Bengtsson, A. Prevalence of current and chronic pain and their influences upon work and healthcare-seeking: a population study. J Rheumatol 2004; 31:1399.
    7. Schmitt, P. Rehabilitation of chronic pain: A multi-disciplinary approach. J Rehabil 1985; 51:72.
    8. Latham, J, Davis, BD. The socioeconomic impact of chronic pain. Disabil Rehabil 1994; 16:39.
    9. Fields, HL. Pain. McGraw-Hill Information Services Company, Health Profession Division, New York, 1987.
    10. Revill, SI, Robinson, JO, Rosen, M, Hogg, MI. The reliability of a linear analogue for evaluating pain. Anaesthesia 1976; 31:1191.
    11. McCaffery, M, Pasero, CL. Pain ratings: The fifth vital sign. Am J Nurs 1997; 97:15.
    12. Melzack, R. The McGill pain questionnaire: Major properties and scoring methods. Pain 1975; 1:277.
    13. Eisendrath, SJ. Psychiatric aspects of chronic pain. Neurology 1995; 45:S26.
    14. Bair, MJ, Robinson, RL, Katon, W, Kroenke, K. Depression and pain comorbidity: a literature review. Arch Intern Med 2003; 163:2433.
    15. Hathaway, SR, McKinly, JC. The Minnesota multiphasic personality inventory manual. Psychological Corporation, New York, 1967.
    16. Fordyce, WE. The validity of pain behavior measurement. In: Pain Measurement and Assessment, Melzack, R (Ed), Raven Press, New York, 1983.
    17. Long, CJ. The relationship between surgical outcome and MMPI profiles in chronic pain patients. J Clin Psychol 1981; 37:744.
     
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    1. 3/5,
      Good information and sources
      Mar 10, 2013
    2. 5/5,
      Very informative!
      Sep 28, 2006
  15. Richard_smoker

    Richard_smoker Gold Member

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    Overview of the treatment of chronic pain

    Zahid H Bajwa, MD
    Carol A Warfield, MD
    R Joshua Wootton, MDiv, PhD

    UpToDate performs a continuous review of over 350 journals and other resources. Updates are added as important new information is published. The literature review for version 14.1 is current through December 2005; this topic was last changed on December 6, 2005. The next version of UpToDate (14.2) will be released in June 2006.

    INTRODUCTION — A number of pharmacologic and non-pharmacologic therapies are available for patients with chronic pain. These treatments are reviewed here. The pathogenesis and evaluation of chronic pain are discussed separately. (See "Definition; pathogenesis; and evaluation of chronic pain").

    NONSTEROIDAL ANTIINFLAMMATORY DRUGS
    — Until fairly recently, the analgesic effect of nonsteroidal antiinflammatory drugs (NSAIDs) was believed to arise exclusively from its peripheral action on the enzyme cyclooxygenase, which plays a central role in inflammatory conditions. It is now known that they work centrally as well, at least in certain pain states [1].
    NSAIDs primarily are indicated for mild to moderate pain, particularly of somatic origin, although a number of newer compounds carry an indication for severe pain. They are frequently used for soft tissue injury, strains, sprains, headaches, and arthritis. They also exert synergy when paired with opioids, producing a dose-sparing effect, but they tend to be underutilized in this regard by many physicians.

    There are many NSAIDs from which to choose (show table 1). There is little literature substantiating improved efficacy of one NSAID over another. Nevertheless, a patient who does not tolerate a particular NSAID may do well on another. Compliance can be improved by switching to a BID or QD preparation. (See "NSAIDs: Therapeutic use and variability of response in adults").
    Side effects — The reluctance of many patients and physicians to use NSAIDs to their full benefit stems in part from the many side effects that may be associated with these drugs. (See "NSAIDs: Overview of adverse effects").

    ·Most NSAIDs interfere with platelet aggregation; two exceptions are choline magnesium trisalicylate [2], and the selective COX-2 inhibitors. (See "Overview of selective COX-2 inhibitors"). Despite its short half-life, aspirin irreversibly inhibits platelet aggregation for the lifetime of the platelet (four to seven days); the inhibitory effect of other NSAIDs lasts about two days.

    ·NSAIDs produce adverse gastrointestinal side effects, including dyspepsia and gastric ulceration. The likelihood varies with the type of NSAID (eg, relative protection, at least over the short-term, with COX-2 inhibitors).

    Food and antacids may help patients tolerate NSAIDs with less dyspepsia. In addition, protection against gastroduodenal toxicity can be achieved with misoprostol, high doses of some H2 blockers, and a proton pump inhibitor.

    ·There are a variety of forms of nephrotoxicity associated with NSAID use, including reversible renal insufficiency due to renal vasoconstriction, acute interstitial nephritis, and a predisposition to acute tubular necrosis in the patient with low renal perfusion. In addition, NSAIDs should be prescribed with caution in patients with hypertension, renal insufficiency, or heart failure.

    ·Other side effects of NSAIDS include hepatic toxicity, even at normally recommended doses; confusion and an inability to concentrate; allergic reactions in some patients who are allergic to aspirin may also be allergic to other NSAIDs. The elevations in liver enzymes are generally mild and reversible with discontinuation of the NSAID. Acetaminophen can produce a more severe form of hepatotoxicity, particularly in chronic alcoholics.

    Patients who are predisposed to NSAID or acetaminophen toxicity should not receive these medications, or should be monitored closely for adverse effects. Beyond these considerations, NSAIDs may be used safely and effectively if attention is given to dosage, duration of therapy, and the development of toxicity.
    OPIOIDS — The role of opioid therapy in the more severe forms of acute pain and in malignant pain is well established, but opioid administration in chronic nonmalignant pain remains controversial [3,4].

    For patients with chronic nonmalignant pain, the decision to begin long-term opioid therapy must be weighed carefully. Patients may receive substantial relief of pain, even in those pain syndromes that are often considered to be resistant to opioid therapy. As an example, at least in the short run, opioids are effective in relieving chronic neuropathic pain [5,6]. A meta-analysis of intermediate term studies with opioids (up to eight weeks) showed a significant reduction in pain scale measurements for patients with neuropathic pain, comparable to results with maximal dose gabapentin [7]. Opioid therapy can be used safely and without the development of tolerance or addiction [8]. Guidelines that have been established for opioid therapy should be followed closely [9,10].
    Patients are candidates for opioid therapy after all other appropriate therapies have failed. A psychological evaluation should take place initially, with an emphasis on uncovering psychological comorbidity that may be interfering with current treatment strategies. It is optimal that patients continue to receive psychological support. A history of past drug abuse may be considered a contraindication to long-term opioid therapy, although this remains controversial. The dispensation of drugs and associated follow-up should be performed by a single physician and pharmacy, allowing maximum consistency and continuity of treatment.

    It is critical for physicians to understand the difference between the terms "physical dependence," "tolerance," and "addiction" when prescribing opioids.

    ·Physical dependence means that the rapid discontinuation of opioid following prolonged administration, usually one month or longer, will result in withdrawal symptoms such as dysphoria, anxiety, and volatility of mood, as well as physical findings such as hypertension, tachycardia, and sweating.

    ·Tolerance is present when increasing amounts of opioid are required to produce an equivalent level of efficacy.

    ·Addiction is a form of psychological dependence and refers to the extreme behavior patterns that are associated with procuring and consuming the drug.

    None, any, or all of these factors may present in patients who take opioids for prolonged periods of time.
    Mechanism of action — Opioids exert their analgesic effect through at least four groups of receptors, and probably other subpopulations as well (show table 2). The distribution of these receptors throughout the body, along with their tissue densities within numerous organ systems, account for the global and varied effects of these drugs.

    The most profound analgesic effects of opioids are mediated at the µ receptors. Within the central nervous system (CNS), µ receptors are found in large numbers in the midbrain periaquaductal gray and the substantial gelatinosa in the dorsal horn of the spinal cord where they induce intense analgesia, and a number of other effects such as bradycardia, sedation, euphoria, physical dependence, and respiratory depression.

    Side effects
    — Many of the side effects of opioids are mediated at multiple sites.

    ·Nausea and vomiting result from activation of the chemoreceptor trigger zone in the medulla and from changes in the vestibular system.

    ·Within the gastrointestinal system, opioids delay gastric emptying and cause constipation via an effect upon the central vagus nerve and the mesenteric plexus in the gut.

    ·The cardiovascular effects of opioids are mediated centrally at the central vagal nucleus and, in the case of morphine, directly in the sinoatrial node. Much of the blood pressure instability that occurs with morphine results from histamine release; there also are direct effects upon venous and arterial vasculature. In general, opioids administered in patients who are not hypovolemic maintain cardiac stability fairly well and depress myocardial contractility only slightly. Meperidine is the notable exception, displaying a mild vagolytic and a negative inotropic effect.

    ·Other opioid actions are seen in the biliary tract, the genitourinary system, the skin, and elsewhere.
    Preparations — Opioids are available in a variety of preparations. In addition to the common PO, IM, and IV routes of administration, they may be given transdermally (fentanyl patch), transmucosally (fentanyl oral), and intraspinally. Hydromorphone is available in a rectal suppository form. It is helpful for the physician to be familiar with a variety of these drugs since there is an enormous amount of patient response variability regarding opioid requirements, as well as a propensity for the development of side effects and biases for or against various agents.

    The body's endogenous antinociceptive mediators (comprising three classes of opioid peptides, the enkephalins, endorphins, and dynorphins) target their receptors and seem to be capable of producing dramatic degrees of analgesia when challenged. The potency of exogenously administered opioids equates to the affinity of these compounds for their binding sites. In pain management, we frequently speak of the equianalgesic dose — that dose of an opioid that produces an equal degree of analgesia with the standard of comparison being morphine sulfate (show table 3).

    In patients requiring the most potent opioids, one study suggested that transdermal fentanyl may be preferable to sustained release oral morphine [11,12]. A randomized study comparing transdermal fentanyl with sustained release oral morphine in 680 patients with chronic low back pain showed equivalent pain relief and less constipation for the group randomly assigned to fentanyl [12]. Stable long-term doses of transdermal fentanyl do not seem to significantly impair the ability to drive a car [13].

    World Health Organization recommendations
    — Much of what is practiced in the use of opioids to manage chronic pain comes from experience with cancer pain. The World Health Organization (WHO) has published guidelines for the pharmacological treatment of cancer pain [14]; many of these strategies also are used in nonmalignant pain. (See "Pharmacologic therapy of cancer pain"). The following is a summary of their recommendations:

    ·Medications should be administered through the most effective and comfortable route allowing patients the maximum control.

    ·Analgesics given for moderate to severe pain are given on a fixed dose schedule around the clock and not on a PRN basis as is frequently (and incorrectly) done. This allows for more consistent pain relief since patients do not have to "play catch-up" with the previous dose that has largely worn off. Patients given analgesics this way are more comfortable and use less medication overall.

    ·The ladder approach developed by the WHO provides for the administration of nonopioid medication (± adjuvants) first. This is followed by the use of mild opioids (eg, codeine) for mild to moderate pain, ± adjuvants, ± nonopioids. For pain that persists, strong opioids (eg, morphine) for moderate to severe pain are employed, ± adjuvants, ± nonopioids.

    ·There is a great deal of interpatient variability. The answer to the question, "How much opioid is enough?" is whatever it takes to relieve the pain without producing intolerable side effects.

    ·Adjuvants are used for enhancing analgesics, controlling side effects, and managing other symptoms that are associated with chronic pain, such as nausea, depression, sedation, insomnia, and anxiety (see below). They also include medication for neuropathic pain, which is not well treated with opioids.

    ·Follow-up closely with patients and look for changes in function and symptoms. Modify drug regimens as the symptoms dictate and continually educate the patient regarding the medication he or she is taking.

    Initiation of therapy — Initiation of opioid therapy begins with the patient and the physician entering into a written contractual agreement, to include the following:
    This should serve as informed consent, and the likelihood of physical dependence and cognitive impairment must be addressed at this time. Female patients of childbearing age must understand the implication of becoming pregnant while on opioids and the likelihood that children will be born physically dependent. Patients agree to obtain prescriptions only from the contracting physician and, preferably, one pharmacy is selected for dispensing these prescriptions. The patient also agrees to take the medication only as prescribed, but provisions should be built-in that provide some latitude for the consumption of more or less medication as symptoms dictate. Patients must be responsible for their written prescriptions, medication, and the arranging of refills during regular office hours, and must plan ahead so as not to run out of medication during weekends or vacation periods. Finally, the patient understands that he/she will be expected to adhere to these conditions and that violating the terms may result in weaning and discontinuation of opioid therapy.

    The initiation of opioid therapy involves titrating the dose of a short-acting (immediate-release) drug upward to effect, with an eye on side effects. The amount of drug used in a 24-hour period is then converted to a sustained release form and administered BID or TID around the clock. If the patient is prone to breakthrough pain, rescue doses of immediate release preparations must be provided for the patient to use on a PRN basis. Two points must be emphasized:

    ·Patients with chronic nonmalignant pain may be candidates for opioid therapy after all other appropriate therapies have failed.

    ·The use of opioids in chronic nonmalignant pain in no way excludes other treatment modalities and, in fact, it is expected that full advantage will be taken of improvements in pain to permit the patient fuller involvement in a multidisciplinary program.
    Spinal delivery systems — Patients who require particularly large doses of opioids, the systemic effect of which becomes intolerable, may be candidates for an implantable spinal delivery system that permits intrathecal administration of opioid, usually morphine. The advantage of this route of administration is the ability to get the opioid directly to the opioid receptors in the spinal cord, thereby reducing the systemic concentration and minimizing side effects. Patients may continue to use PO analgesics on a PRN basis. However, the newer pump technology features programming that permits dosing to be matched to variations in day-to-day requirements. Their small size and complete implantation allows the patient a tremendous degree of freedom in daily life.

    These devices can be useful in cancer patients as well, although, given the high cost of this technology, patients should have a life expectancy in excess of three to six months. When this is not the case, a similar intrathecal or epidural catheter system may be used with a small externally driven pump. These systems cost far less but actually allow for a greater amount of dosing flexibility, which is particularly useful in the later stages of a cancer patient's life, when dose escalation may be fairly rapid. In addition, the neuraxial administration of other drugs such as local anesthetics and clonidine may be used.
    TramadolTramadol (Ultram™) is a somewhat novel analgesic that has some activity at Mu receptors. It also inhibits the reuptake of serotonin and norepinephrine and may provide analgesia through this mechanism. Its side effect profile is similar to that of other weak opioids, although the incidence of gastric upset seems to be higher. Seizures are an additional risk, particularly in patients on antidepressants, neuroleptics, or other drugs that decrease the seizure threshold.

    Tramadol is extensively metabolized with one pharmacologically active metabolite, M1. This is a P-450 generated molecule that is subject to enzyme induction and inhibition. The dose is reduced in patients with hepatic dysfunction and in the elderly.

    TRICYCLIC ANTIDEPRESSANTS
    — None of the tricyclic antidepressants (TCAs) carries an indication for pain management. Nevertheless, they remain a pharmacological mainstay in a variety of chronic pain states, with or without coexisting depression.
    Amitriptyline has been the most widely studied TCA in chronic pain [15,16], although a number of others, including doxepin, imipramine, nortriptyline, and desipramine also have been used with success. TCAs are believed to have independent analgesic effects as well as an ability to relieve the depressive symptoms associated with chronic pain.

    The mechanism of their analgesic action is uncertain; it has been theorized that the analgesic properties are associated with their action as serotonin and norepinephrine reuptake inhibitors. Consistent with this theory is the observation that TCAs with the greatest effect upon serotonin seem to have the greatest analgesic effect. There is also some evidence that TCAs potentiate the endogenous opioid system [17]. Still, it remains to be explained why a drug like fluoxetine, a potent serotonin reuptake inhibitor, has little or no analgesic effect on its own, but seems to add to the efficacy of some TCAs.

    TCAs prescribed for chronic pain have typically been given at doses somewhat lower than those used in depression, although higher doses have provided superior analgesia in some studies. Some patients respond only as the dose is steadily increased.
    and TCAs can cause wide-ranging adverse effects. Aside from anticholinergic effects (strong for amitriptyline, imipramine, and doxepin, and minimal for nortriptylinedesipramine), most of the more troubling or serious side effects involve the gastrointestinal, cardiovascular, and neurologic systems (show table 4 and show table 5).

    Physicians must explain to the patient why TCAs are used, how to administer them, and what benefits and side effects might be expected. Sedation, a well-known side effect of TCAs, can be turned into a benefit since many chronic pain patients suffer from sleep disturbances; the induction of sleep occurs one to three hours following ingestion. Patients should be instructed to match this period with their normal sleep interval. If they awake with a morning "hangover," it should be taken earlier in the evening. Stool softeners can be used if there is a tendency toward constipation.

    It is also important for patients to know that many of the unpleasant side effects, such as dry mouth, mental clouding, and others, may diminish in days to weeks. Encourage the patient to "ride it out" and provide them with a handout that reinforces what you have told them. When a particular TCA is not tolerated, sometimes decreasing the dose or substituting a different member of this class, one with fewer anticholinergic effects, will make the difference.

    Patients should also understand that although analgesia may occur in days, it frequently will take weeks to obtain any significant benefit. Doses should be increased gradually to the point of effect or intolerable side effects; when one antidepressant does not work, another can be tried. The process of finding an effective TCA can be slow and frustrating but in many cases worthwhile.
    TCAs (mainly those with greater anticholinergic effects) are relatively contraindicated in patients with severe cardiac disease, particularly conduction disturbances; obtaining a pretreatment ECG is recommended. They should also be avoided in patients with severe gastrointestinal dysfunction since such symptoms may be exacerbated. Desipramine and nortriptyline can be used safely in older patients; their starting dose should be reduced by one-half, and patients should be watched carefully for untoward effects as the doses are escalated slowly.

    ANTICONVULSANTS
    — A number of anticonvulsants are effective for chronic pain therapy, particularly for lancinating pain [18]. Phenytoin, carbamazepine, valproic acid, and clonazepam, as well as the newer agents, gabapentin and lamotrigine, have all been used, frequently with impressive results. Their mechanisms of action are different and, in the case of the last three agents, are not fully understood. Phenytoin's activity seems to be related to its membrane stabilizing action. Carbamazepine, which is pharmacologically related to the TCAs, prevents repeated discharges in neurons, an action that is consistent with its ability to relieve lancinating pain. Valproic acid and clonazepam are believed to work through enhancement of GABA inhibitory systems.

    Beyond the consistent selection of carbamazepine for trigeminal neuralgia, physicians vary widely in their preferences for the use of these drugs. Many physicians will begin with gabapentin since it appears to be well tolerated, even at high doses, and plasma levels do not need to be followed as they do with phenytoin and carbamazepine [19].

    A complete blood count and baseline liver function tests should be obtained prior to starting patients on older anticonvulsants such as dilantin, carbamazepine, and valproic acid. It is recommended that blood tests be followed for the first three weeks and periodically thereafter. Blood levels do not generally correlate with efficacy; doses are gradually titrated upward until pain symptoms are improved or adverse effects occur. Blood levels may be helpful in determining compliance during dose escalations.

    A technique practiced in some pain management centers involves loading the patient with IV phenytoin (10 to 15 mg/kg) in a monitored setting and following pain scores closely. In patients with significant responses, oral phenytoin is started at 200 to 300 mg at bedtime.

    ZICONOTIDE [ — Ziconotide is a novel intrathecal pain medication that was approved in 2004 by the US FDA for use in patients who are intolerant of or refractory to other treatments for pain including intrathecal morphine20,21]. Ziconotide binds to neural N-type calcium channels. It is a synthetic drug with an amino acid sequence derived from marine sea snail venom (a conopeptide); several other drugs in this class are also under development [22].

    A randomized trial in 111 adults with cancer or AIDS and refractory pain found that more patients had moderate to complete relief of pain with intrathecal ziconotide than with placebo (53 versus 18 percent) [23]. Central nervous system side effects were significantly more common than with placebo (83 versus 35 percent) and included dizziness, nystagmus, somnolence, and confusion. The US prescribing information for ziconotide includes a "black box" warning about neurologic impairment and psychiatric symptoms and states that patients with a preexisting history of psychosis should not be treated with ziconotide [20].

    There is little clinical experience with ziconotide, and it can produce serious side effects. We recommend that, at this point, it only be used in patients with no other reasonable options for pain control.

    ADJUVANT MEDICATIONS
    — The usefulness of pairing adjuvant agents with pain medications is well known by pain management specialists. Some are used to treat the side effects associated with pain medications, while others potentiate analgesia. With adjuvant agents, or with the more established and proved pharmacological intervention for pain, the goal is always analgesia and the relief of emotional distress. When chronic pain has remained intractable or largely inert to the recognized and well-documented medication regimens, a certain amount of exploration and innovation may be medically indicated.

    Prevention of opioid side effects
    — Patients who are treated with opioids, either for short-term use or chronic administration, can experience a variety of unpleasant side effects such as nausea and vomiting, abdominal cramping, pruritus, sedation, changes in mentation, and constipation. Some of these untoward effects may subside with time, but meticulous attention to treating them as they occur can make the difference between tolerance of the medication with good analgesic effect versus complete treatment failure.

    A bowel regimen aimed at preventing constipation should be initiated in patients treated with opioids, particularly for those who are prone to this condition. A variety of antihistamines and antiemetics are available to treat pruritus and nausea, respectively, and should be instituted early when patients require them.
    Stimulants have been used with good effect when sedation is an issue with opioids, particularly in cancer patients requiring large doses. They also appear to possess analgesic, antidepressant, and euphoric effects. The precise mechanism of action of these is not clear; however, it is likely related to their sympathomimetic action with effects upon serotonin, norepinephrine and the endogenous opioids. The most commonly used stimulants are dextroamphetamine, (Dexedrine, 5 to 10 mg in the morning and up to 20 mg a few hours later) and methylphenidate (Ritalin, 10 mg in the morning, up to 40 mg a few hours later). These drugs must be used cautiously since they are associated with tolerance and side effects of their own, and there are numerous contraindications to their use.

    Benzodiazepines Benzodiazepines may be utilized in patients who would benefit from anxiolysis. These are commonly employed in cancer patients and in non-malignant pain complicated by anxiety disorder (show table 6). The disadvantage of this class of drugs relates to their addictive potential, as well as their potentiation of sedative effects and respiratory depression in patients who use opioids concurrently. Clonazepam is especially useful for neuropathic pain.
    Antispasmodics — A wide variety of pain conditions, both acute and chronic, may be accompanied by painful muscle spasm. Antispasmodics can be useful in treating this aspect of the patient's symptoms, but their action may be more the result of sedation rather than muscle relaxation. Commonly used muscle relaxants are listed in Table 7 (show table 7). These medications may also cause CNS depression and should be used cautiously when combined with other CNS depressant medications.

    Other antidepressants — Documentation of analgesic effects with more serotonergically responsive antidepressants is less established than with those whose principal action is directed toward both norepinephrine and serotonin or norepinephrine only. However, agents with a high degree of noradrenergic activity may not be well tolerated, especially in the elderly, because of their association with autonomic, cardiac, and ocular side effects. Other patients whose pain has remained refractory to one or more trials of the TCAs or who have experienced accompanying increased appetite and weight gain, sedation, confusion or cognitive impairment, intolerable dry mouth, or uncontrollable perspiring may find that Selective Serotonin Reuptake Inhibitors (SSRIs) are effective adjunctive agents in the pharmacology of pain management.

    The mechanism of analgesia with SSRIs is less well documented and less well understood than with the TCAs, but may be associated with the primary relief of depression, especially in somatically-expressive instances of depression. Such cases, sometimes formerly referred to as "masked" depression, may be characterized by the patient's tendency to deny or minimize sad mood and dysphoric ideation, while mobilizing somatization as a defense against depression. In many of these patients, effective treatment of the primary depression can ameliorate or even resolve the complaint of chronic pain. In other patients, for whom the symptoms of depression are a complicating feature and sometimes natural sequel to life with chronic pain, favorable response to an SSRI will greatly relieve the subjective experience of distress and, therefore, the affective and emotional intensity with which physical pain is experienced.

    The serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine may also be useful in the treatment of chronic pain. As an example, a randomized trial of venlafaxine in patients with painful polyneuropathy found that venlafaxine was superior to placebo and was similar in efficacy to imipramine [24].

    ADJUNCTIVE THERAPIES
    — Adjunctive therapies encompass a wide array of treatments which may be grouped into the physical interventions, including physical therapy, acupuncture, chiropractic manipulation, massage, and others, and the psychoeducational interventions such as cognitive-behavioral therapy, family therapy, patient education, and psychotherapy. Many patients view these approaches with a sense of skepticism, believing them not to be helpful or appropriate to their circumstances. However, more patients are beginning to embrace them as the media attention these techniques are given increases.
    There is a wealth of anecdotal experience suggesting that when chosen carefully and applied properly, adjunctive therapies enhance the efficacy of pharmacological and interventional therapies. However, data in support of this are lacking. One meta-analysis considering the role of adjunctive therapies in the management of chronic nonmalignant pain reported that the combination of exercise and psychoeducational approaches can lead to a significant reduction in pain and improvement in functional status for a number of musculoskeletal conditions [25]. It was concluded that as chronic pain is a summation of physical and psychological derangements, managing it successfully requires addressing all of its aspects. This begins with making patients aware of what is available therapeutically and explaining what each component therapy offers. There is evidence that combination therapies are more effective than any single approach for maintaining long-term gains. Consideration is also given to the issue of relapse prevention through the integration behavioral work.
    There has been criticism of the multidisciplinary approach as being overly costly and largely ineffective. Here, too, good data are lacking. Part of the problem has to do with the inherent difficulty in measuring improvement. Return-to-work has been considered a useful measure of efficacy of treatment due to its relative objectivity and its relevance. One group published a review and meta-analysis of the literature on the efficacy of nonsurgical, multidisciplinary treatment of chronic pain, focusing upon the "return to work" outcome variable [26]. Despite the study's acknowledged flaws, they demonstrated:

    ·A clear trend in the proportion of patients returning to work (20 to 54 percent)

    ·That the improvement was due to treatment

    ·That benefits were not temporary (follow-up ranged from 1 to 60 months).

    REFERENCES
    1. McCormack, K. Non-steriodal anti-inflammatory drugs and spinal nociceptive processing. Pain 1994; 59:9.
    2. Stuart, JJ, Pisko, EJ. Choline magnesium trisalicylate does not impair platelet aggregation. Pharmatherapeutica 1981; 2:547.
    3. Ballantyne, JC, Mao, J. Opioid therapy for chronic pain. N Engl J Med 2003; 349:1943.
    4. Portenoy, RK. Opioid therapy for chronic nonmalignant pain: A review of the critical issues. J Pain Symptom Manage 1996; 11:203.
    5. Rowbotham, MC, Twilling, L, Davies, PS, et al. Oral opioid therapy for chronic peripheral and central neuropathic pain. N Engl J Med 2003; 348:1223.
    6. Foley, KM. Opioids and chronic neuropathic pain. N Engl J Med 2003; 348:1279.
    7. Eisenberg, E, McNicol, ED, Carr, DB. Efficacy and safety of opioid agonists in the treatment ofneuropathic pain of nonmalignant origin. JAMA 2005; 293:3043.
    8. Joranson, DE, Ryan, KM, Gilson, AM, Dahl, JL. Trends in medical use and abuse of opioid analgesics. JAMA 2000; 283:1710.
    9. Portenoy, RK. Chronic opioid therapy in nonmalignant pain: From models to practice. APS Journal 1992; 1:258.
    10. Portenoy, RK. Opioid therapy for chronic nonmalignant pain: Current status. In: Fields, HL, Liebeskind, JC, eds. Progress in pain research and management, vol I. Pharmacologic approaches to the treatment of chronic pain: new concepts and critical issues. Seattle: IASP Publications 1994; 247.
    11. Allan, L, Hays, H, Jensen, NH, et al. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ 2001; 322:1154.
    12. Allan, L, Richarz, U, Simpson, K, Slappendel, R. Transdermal fentanyl versus sustained release oral morphine in strong-opioid naive patients with chronic low back pain. Spine 2005; 30:2484.
    13. Sabatowski, R, Schwalen, S, Rettig, K, et al. Driving ability under long-term treatment with transdermal fentanyl. J Pain Symptom Manage 2003; 25:38.
    14. World Health Organization. Cancer pain relief. Geneva: World Health Organization, 1990.
    15. Pilowsky, I, Hallett, EC, Bassett, DL, et al. A controlled study of amitriptyline in the treatment of chronic pain. Pain 1982; 14:169.
    16. Jaeschke, R, Adachi, J, Guyatt, G, et al. Clinical usefulness of amitriptyline in fibromyalgia: The results of 23 N-of-1 randomized controlled trials. J Rheumatol 1991; 18:447.
    17. Godfrey, RG. A guide to the understanding and use of tricyclic antidepressants in the overall management of fibromyalgia and other chronic pain syndromes. Arch Intern Med 1996; 156:1047.
    18. Swerdlow, M. Review: Anticonvulsant drugs and chronic pain. Clin Neuropharmacol 1984; 7:51.
    19. Handforth, A, Treiman, DM. Efficacy and tolerance of long-term, high-dose gabapentin: Additional observations. Epilepsia 1994; 35:1032.
    20. www.prialt.com/downloads/product_information.pdf (Accessed 3/7/05).
    21. Ziconotide (Prialt) for chronic pain. Med Lett Drugs Ther 2005; 47:103.
    22. Sharp, D. Novel pain relief via marine snails. Lancet 2005; 366:439.
    23. Staats, PS, Yearwood, T, Charapata, SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA 2004; 291:63.
    24. Sindrup, SH, Bach, FW, Madsen, C, et al. Venlafaxine versus imipramine in painful polyneuropathy: A randomized, controlled trial. Neurology 2003; 60:1284.
    25. Allegrante, JP. The role of adjunctive therapy in the management of nonmalignant pain. Am J Med 1996; 101:33S.
    26. Cutler, RB, Fishbain, DA, Rosomoff, HL, et al. Does non-surgical pain center treatment of chronic pain return patients to work? Spine 1994; 19:643.
     
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  16. Richard_smoker

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    Overview of the treatment of chronic pain

    Zahid H Bajwa, MD
    Carol A Warfield, MD
    R Joshua Wootton, MDiv, PhD

    UpToDate performs a continuous review of over 350 journals and other resources. Updates are added as important new information is published. The literature review for version 14.1 is current through December 2005; this topic was last changed on December 6, 2005. The next version of UpToDate (14.2) will be released in June 2006.

    INTRODUCTION — A number of pharmacologic and non-pharmacologic therapies are available for patients with chronic pain. These treatments are reviewed here. The pathogenesis and evaluation of chronic pain are discussed separately. (See "Definition; pathogenesis; and evaluation of chronic pain").

    NONSTEROIDAL ANTIINFLAMMATORY DRUGS
    — Until fairly recently, the analgesic effect of nonsteroidal antiinflammatory drugs (NSAIDs) was believed to arise exclusively from its peripheral action on the enzyme cyclooxygenase, which plays a central role in inflammatory conditions. It is now known that they work centrally as well, at least in certain pain states [1].
    NSAIDs primarily are indicated for mild to moderate pain, particularly of somatic origin, although a number of newer compounds carry an indication for severe pain. They are frequently used for soft tissue injury, strains, sprains, headaches, and arthritis. They also exert synergy when paired with opioids, producing a dose-sparing effect, but they tend to be underutilized in this regard by many physicians.

    There are many NSAIDs from which to choose (show table 1). There is little literature substantiating improved efficacy of one NSAID over another. Nevertheless, a patient who does not tolerate a particular NSAID may do well on another. Compliance can be improved by switching to a BID or QD preparation. (See "NSAIDs: Therapeutic use and variability of response in adults").
    Side effects — The reluctance of many patients and physicians to use NSAIDs to their full benefit stems in part from the many side effects that may be associated with these drugs. (See "NSAIDs: Overview of adverse effects").

    ·Most NSAIDs interfere with platelet aggregation; two exceptions are choline magnesium trisalicylate [2], and the selective COX-2 inhibitors. (See "Overview of selective COX-2 inhibitors"). Despite its short half-life, aspirin irreversibly inhibits platelet aggregation for the lifetime of the platelet (four to seven days); the inhibitory effect of other NSAIDs lasts about two days.

    ·NSAIDs produce adverse gastrointestinal side effects, including dyspepsia and gastric ulceration. The likelihood varies with the type of NSAID (eg, relative protection, at least over the short-term, with COX-2 inhibitors).

    Food and antacids may help patients tolerate NSAIDs with less dyspepsia. In addition, protection against gastroduodenal toxicity can be achieved with misoprostol, high doses of some H2 blockers, and a proton pump inhibitor.

    ·There are a variety of forms of nephrotoxicity associated with NSAID use, including reversible renal insufficiency due to renal vasoconstriction, acute interstitial nephritis, and a predisposition to acute tubular necrosis in the patient with low renal perfusion. In addition, NSAIDs should be prescribed with caution in patients with hypertension, renal insufficiency, or heart failure.

    ·Other side effects of NSAIDS include hepatic toxicity, even at normally recommended doses; confusion and an inability to concentrate; allergic reactions in some patients who are allergic to aspirin may also be allergic to other NSAIDs. The elevations in liver enzymes are generally mild and reversible with discontinuation of the NSAID. Acetaminophen can produce a more severe form of hepatotoxicity, particularly in chronic alcoholics.

    Patients who are predisposed to NSAID or acetaminophen toxicity should not receive these medications, or should be monitored closely for adverse effects. Beyond these considerations, NSAIDs may be used safely and effectively if attention is given to dosage, duration of therapy, and the development of toxicity.
    OPIOIDS — The role of opioid therapy in the more severe forms of acute pain and in malignant pain is well established, but opioid administration in chronic nonmalignant pain remains controversial [3,4].

    For patients with chronic nonmalignant pain, the decision to begin long-term opioid therapy must be weighed carefully. Patients may receive substantial relief of pain, even in those pain syndromes that are often considered to be resistant to opioid therapy. As an example, at least in the short run, opioids are effective in relieving chronic neuropathic pain [5,6]. A meta-analysis of intermediate term studies with opioids (up to eight weeks) showed a significant reduction in pain scale measurements for patients with neuropathic pain, comparable to results with maximal dose gabapentin [7]. Opioid therapy can be used safely and without the development of tolerance or addiction [8]. Guidelines that have been established for opioid therapy should be followed closely [9,10].
    Patients are candidates for opioid therapy after all other appropriate therapies have failed. A psychological evaluation should take place initially, with an emphasis on uncovering psychological comorbidity that may be interfering with current treatment strategies. It is optimal that patients continue to receive psychological support. A history of past drug abuse may be considered a contraindication to long-term opioid therapy, although this remains controversial. The dispensation of drugs and associated follow-up should be performed by a single physician and pharmacy, allowing maximum consistency and continuity of treatment.

    It is critical for physicians to understand the difference between the terms "physical dependence," "tolerance," and "addiction" when prescribing opioids.

    ·Physical dependence means that the rapid discontinuation of opioid following prolonged administration, usually one month or longer, will result in withdrawal symptoms such as dysphoria, anxiety, and volatility of mood, as well as physical findings such as hypertension, tachycardia, and sweating.

    ·Tolerance is present when increasing amounts of opioid are required to produce an equivalent level of efficacy.

    ·Addiction is a form of psychological dependence and refers to the extreme behavior patterns that are associated with procuring and consuming the drug.

    None, any, or all of these factors may present in patients who take opioids for prolonged periods of time.
    Mechanism of action — Opioids exert their analgesic effect through at least four groups of receptors, and probably other subpopulations as well (show table 2). The distribution of these receptors throughout the body, along with their tissue densities within numerous organ systems, account for the global and varied effects of these drugs.

    The most profound analgesic effects of opioids are mediated at the µ receptors. Within the central nervous system (CNS), µ receptors are found in large numbers in the midbrain periaquaductal gray and the substantial gelatinosa in the dorsal horn of the spinal cord where they induce intense analgesia, and a number of other effects such as bradycardia, sedation, euphoria, physical dependence, and respiratory depression.

    Side effects
    — Many of the side effects of opioids are mediated at multiple sites.

    ·Nausea and vomiting result from activation of the chemoreceptor trigger zone in the medulla and from changes in the vestibular system.

    ·Within the gastrointestinal system, opioids delay gastric emptying and cause constipation via an effect upon the central vagus nerve and the mesenteric plexus in the gut.

    ·The cardiovascular effects of opioids are mediated centrally at the central vagal nucleus and, in the case of morphine, directly in the sinoatrial node. Much of the blood pressure instability that occurs with morphine results from histamine release; there also are direct effects upon venous and arterial vasculature. In general, opioids administered in patients who are not hypovolemic maintain cardiac stability fairly well and depress myocardial contractility only slightly. Meperidine is the notable exception, displaying a mild vagolytic and a negative inotropic effect.

    ·Other opioid actions are seen in the biliary tract, the genitourinary system, the skin, and elsewhere.
    Preparations — Opioids are available in a variety of preparations. In addition to the common PO, IM, and IV routes of administration, they may be given transdermally (fentanyl patch), transmucosally (fentanyl oral), and intraspinally. Hydromorphone is available in a rectal suppository form. It is helpful for the physician to be familiar with a variety of these drugs since there is an enormous amount of patient response variability regarding opioid requirements, as well as a propensity for the development of side effects and biases for or against various agents.

    The body's endogenous antinociceptive mediators (comprising three classes of opioid peptides, the enkephalins, endorphins, and dynorphins) target their receptors and seem to be capable of producing dramatic degrees of analgesia when challenged. The potency of exogenously administered opioids equates to the affinity of these compounds for their binding sites. In pain management, we frequently speak of the equianalgesic dose — that dose of an opioid that produces an equal degree of analgesia with the standard of comparison being morphine sulfate (show table 3).

    In patients requiring the most potent opioids, one study suggested that transdermal fentanyl may be preferable to sustained release oral morphine [11,12]. A randomized study comparing transdermal fentanyl with sustained release oral morphine in 680 patients with chronic low back pain showed equivalent pain relief and less constipation for the group randomly assigned to fentanyl [12]. Stable long-term doses of transdermal fentanyl do not seem to significantly impair the ability to drive a car [13].

    World Health Organization recommendations
    — Much of what is practiced in the use of opioids to manage chronic pain comes from experience with cancer pain. The World Health Organization (WHO) has published guidelines for the pharmacological treatment of cancer pain [14]; many of these strategies also are used in nonmalignant pain. (See "Pharmacologic therapy of cancer pain"). The following is a summary of their recommendations:

    ·Medications should be administered through the most effective and comfortable route allowing patients the maximum control.

    ·Analgesics given for moderate to severe pain are given on a fixed dose schedule around the clock and not on a PRN basis as is frequently (and incorrectly) done. This allows for more consistent pain relief since patients do not have to "play catch-up" with the previous dose that has largely worn off. Patients given analgesics this way are more comfortable and use less medication overall.

    ·The ladder approach developed by the WHO provides for the administration of nonopioid medication (± adjuvants) first. This is followed by the use of mild opioids (eg, codeine) for mild to moderate pain, ± adjuvants, ± nonopioids. For pain that persists, strong opioids (eg, morphine) for moderate to severe pain are employed, ± adjuvants, ± nonopioids.

    ·There is a great deal of interpatient variability. The answer to the question, "How much opioid is enough?" is whatever it takes to relieve the pain without producing intolerable side effects.

    ·Adjuvants are used for enhancing analgesics, controlling side effects, and managing other symptoms that are associated with chronic pain, such as nausea, depression, sedation, insomnia, and anxiety (see below). They also include medication for neuropathic pain, which is not well treated with opioids.

    ·Follow-up closely with patients and look for changes in function and symptoms. Modify drug regimens as the symptoms dictate and continually educate the patient regarding the medication he or she is taking.

    Initiation of therapy — Initiation of opioid therapy begins with the patient and the physician entering into a written contractual agreement, to include the following:
    This should serve as informed consent, and the likelihood of physical dependence and cognitive impairment must be addressed at this time. Female patients of childbearing age must understand the implication of becoming pregnant while on opioids and the likelihood that children will be born physically dependent. Patients agree to obtain prescriptions only from the contracting physician and, preferably, one pharmacy is selected for dispensing these prescriptions. The patient also agrees to take the medication only as prescribed, but provisions should be built-in that provide some latitude for the consumption of more or less medication as symptoms dictate. Patients must be responsible for their written prescriptions, medication, and the arranging of refills during regular office hours, and must plan ahead so as not to run out of medication during weekends or vacation periods. Finally, the patient understands that he/she will be expected to adhere to these conditions and that violating the terms may result in weaning and discontinuation of opioid therapy.

    The initiation of opioid therapy involves titrating the dose of a short-acting (immediate-release) drug upward to effect, with an eye on side effects. The amount of drug used in a 24-hour period is then converted to a sustained release form and administered BID or TID around the clock. If the patient is prone to breakthrough pain, rescue doses of immediate release preparations must be provided for the patient to use on a PRN basis. Two points must be emphasized:

    ·Patients with chronic nonmalignant pain may be candidates for opioid therapy after all other appropriate therapies have failed.

    ·The use of opioids in chronic nonmalignant pain in no way excludes other treatment modalities and, in fact, it is expected that full advantage will be taken of improvements in pain to permit the patient fuller involvement in a multidisciplinary program.
    Spinal delivery systems — Patients who require particularly large doses of opioids, the systemic effect of which becomes intolerable, may be candidates for an implantable spinal delivery system that permits intrathecal administration of opioid, usually morphine. The advantage of this route of administration is the ability to get the opioid directly to the opioid receptors in the spinal cord, thereby reducing the systemic concentration and minimizing side effects. Patients may continue to use PO analgesics on a PRN basis. However, the newer pump technology features programming that permits dosing to be matched to variations in day-to-day requirements. Their small size and complete implantation allows the patient a tremendous degree of freedom in daily life.

    These devices can be useful in cancer patients as well, although, given the high cost of this technology, patients should have a life expectancy in excess of three to six months. When this is not the case, a similar intrathecal or epidural catheter system may be used with a small externally driven pump. These systems cost far less but actually allow for a greater amount of dosing flexibility, which is particularly useful in the later stages of a cancer patient's life, when dose escalation may be fairly rapid. In addition, the neuraxial administration of other drugs such as local anesthetics and clonidine may be used.
    TramadolTramadol (Ultram™) is a somewhat novel analgesic that has some activity at Mu receptors. It also inhibits the reuptake of serotonin and norepinephrine and may provide analgesia through this mechanism. Its side effect profile is similar to that of other weak opioids, although the incidence of gastric upset seems to be higher. Seizures are an additional risk, particularly in patients on antidepressants, neuroleptics, or other drugs that decrease the seizure threshold.

    Tramadol is extensively metabolized with one pharmacologically active metabolite, M1. This is a P-450 generated molecule that is subject to enzyme induction and inhibition. The dose is reduced in patients with hepatic dysfunction and in the elderly.

    TRICYCLIC ANTIDEPRESSANTS
    — None of the tricyclic antidepressants (TCAs) carries an indication for pain management. Nevertheless, they remain a pharmacological mainstay in a variety of chronic pain states, with or without coexisting depression.
    Amitriptyline has been the most widely studied TCA in chronic pain [15,16], although a number of others, including doxepin, imipramine, nortriptyline, and desipramine also have been used with success. TCAs are believed to have independent analgesic effects as well as an ability to relieve the depressive symptoms associated with chronic pain.

    The mechanism of their analgesic action is uncertain; it has been theorized that the analgesic properties are associated with their action as serotonin and norepinephrine reuptake inhibitors. Consistent with this theory is the observation that TCAs with the greatest effect upon serotonin seem to have the greatest analgesic effect. There is also some evidence that TCAs potentiate the endogenous opioid system [17]. Still, it remains to be explained why a drug like fluoxetine, a potent serotonin reuptake inhibitor, has little or no analgesic effect on its own, but seems to add to the efficacy of some TCAs.

    TCAs prescribed for chronic pain have typically been given at doses somewhat lower than those used in depression, although higher doses have provided superior analgesia in some studies. Some patients respond only as the dose is steadily increased.
    and TCAs can cause wide-ranging adverse effects. Aside from anticholinergic effects (strong for amitriptyline, imipramine, and doxepin, and minimal for nortriptylinedesipramine), most of the more troubling or serious side effects involve the gastrointestinal, cardiovascular, and neurologic systems (show table 4 and show table 5).

    Physicians must explain to the patient why TCAs are used, how to administer them, and what benefits and side effects might be expected. Sedation, a well-known side effect of TCAs, can be turned into a benefit since many chronic pain patients suffer from sleep disturbances; the induction of sleep occurs one to three hours following ingestion. Patients should be instructed to match this period with their normal sleep interval. If they awake with a morning "hangover," it should be taken earlier in the evening. Stool softeners can be used if there is a tendency toward constipation.

    It is also important for patients to know that many of the unpleasant side effects, such as dry mouth, mental clouding, and others, may diminish in days to weeks. Encourage the patient to "ride it out" and provide them with a handout that reinforces what you have told them. When a particular TCA is not tolerated, sometimes decreasing the dose or substituting a different member of this class, one with fewer anticholinergic effects, will make the difference.

    Patients should also understand that although analgesia may occur in days, it frequently will take weeks to obtain any significant benefit. Doses should be increased gradually to the point of effect or intolerable side effects; when one antidepressant does not work, another can be tried. The process of finding an effective TCA can be slow and frustrating but in many cases worthwhile.
    TCAs (mainly those with greater anticholinergic effects) are relatively contraindicated in patients with severe cardiac disease, particularly conduction disturbances; obtaining a pretreatment ECG is recommended. They should also be avoided in patients with severe gastrointestinal dysfunction since such symptoms may be exacerbated. Desipramine and nortriptyline can be used safely in older patients; their starting dose should be reduced by one-half, and patients should be watched carefully for untoward effects as the doses are escalated slowly.

    ANTICONVULSANTS
    — A number of anticonvulsants are effective for chronic pain therapy, particularly for lancinating pain [18]. Phenytoin, carbamazepine, valproic acid, and clonazepam, as well as the newer agents, gabapentin and lamotrigine, have all been used, frequently with impressive results. Their mechanisms of action are different and, in the case of the last three agents, are not fully understood. Phenytoin's activity seems to be related to its membrane stabilizing action. Carbamazepine, which is pharmacologically related to the TCAs, prevents repeated discharges in neurons, an action that is consistent with its ability to relieve lancinating pain. Valproic acid and clonazepam are believed to work through enhancement of GABA inhibitory systems.

    Beyond the consistent selection of carbamazepine for trigeminal neuralgia, physicians vary widely in their preferences for the use of these drugs. Many physicians will begin with gabapentin since it appears to be well tolerated, even at high doses, and plasma levels do not need to be followed as they do with phenytoin and carbamazepine [19].

    A complete blood count and baseline liver function tests should be obtained prior to starting patients on older anticonvulsants such as dilantin, carbamazepine, and valproic acid. It is recommended that blood tests be followed for the first three weeks and periodically thereafter. Blood levels do not generally correlate with efficacy; doses are gradually titrated upward until pain symptoms are improved or adverse effects occur. Blood levels may be helpful in determining compliance during dose escalations.

    A technique practiced in some pain management centers involves loading the patient with IV phenytoin (10 to 15 mg/kg) in a monitored setting and following pain scores closely. In patients with significant responses, oral phenytoin is started at 200 to 300 mg at bedtime.

    ZICONOTIDE [ — Ziconotide is a novel intrathecal pain medication that was approved in 2004 by the US FDA for use in patients who are intolerant of or refractory to other treatments for pain including intrathecal morphine20,21]. Ziconotide binds to neural N-type calcium channels. It is a synthetic drug with an amino acid sequence derived from marine sea snail venom (a conopeptide); several other drugs in this class are also under development [22].

    A randomized trial in 111 adults with cancer or AIDS and refractory pain found that more patients had moderate to complete relief of pain with intrathecal ziconotide than with placebo (53 versus 18 percent) [23]. Central nervous system side effects were significantly more common than with placebo (83 versus 35 percent) and included dizziness, nystagmus, somnolence, and confusion. The US prescribing information for ziconotide includes a "black box" warning about neurologic impairment and psychiatric symptoms and states that patients with a preexisting history of psychosis should not be treated with ziconotide [20].

    There is little clinical experience with ziconotide, and it can produce serious side effects. We recommend that, at this point, it only be used in patients with no other reasonable options for pain control.

    ADJUVANT MEDICATIONS
    — The usefulness of pairing adjuvant agents with pain medications is well known by pain management specialists. Some are used to treat the side effects associated with pain medications, while others potentiate analgesia. With adjuvant agents, or with the more established and proved pharmacological intervention for pain, the goal is always analgesia and the relief of emotional distress. When chronic pain has remained intractable or largely inert to the recognized and well-documented medication regimens, a certain amount of exploration and innovation may be medically indicated.

    Prevention of opioid side effects
    — Patients who are treated with opioids, either for short-term use or chronic administration, can experience a variety of unpleasant side effects such as nausea and vomiting, abdominal cramping, pruritus, sedation, changes in mentation, and constipation. Some of these untoward effects may subside with time, but meticulous attention to treating them as they occur can make the difference between tolerance of the medication with good analgesic effect versus complete treatment failure.

    A bowel regimen aimed at preventing constipation should be initiated in patients treated with opioids, particularly for those who are prone to this condition. A variety of antihistamines and antiemetics are available to treat pruritus and nausea, respectively, and should be instituted early when patients require them.
    Stimulants have been used with good effect when sedation is an issue with opioids, particularly in cancer patients requiring large doses. They also appear to possess analgesic, antidepressant, and euphoric effects. The precise mechanism of action of these is not clear; however, it is likely related to their sympathomimetic action with effects upon serotonin, norepinephrine and the endogenous opioids. The most commonly used stimulants are dextroamphetamine, (Dexedrine, 5 to 10 mg in the morning and up to 20 mg a few hours later) and methylphenidate (Ritalin, 10 mg in the morning, up to 40 mg a few hours later). These drugs must be used cautiously since they are associated with tolerance and side effects of their own, and there are numerous contraindications to their use.

    Benzodiazepines Benzodiazepines may be utilized in patients who would benefit from anxiolysis. These are commonly employed in cancer patients and in non-malignant pain complicated by anxiety disorder (show table 6). The disadvantage of this class of drugs relates to their addictive potential, as well as their potentiation of sedative effects and respiratory depression in patients who use opioids concurrently. Clonazepam is especially useful for neuropathic pain.
    Antispasmodics — A wide variety of pain conditions, both acute and chronic, may be accompanied by painful muscle spasm. Antispasmodics can be useful in treating this aspect of the patient's symptoms, but their action may be more the result of sedation rather than muscle relaxation. Commonly used muscle relaxants are listed in Table 7 (show table 7). These medications may also cause CNS depression and should be used cautiously when combined with other CNS depressant medications.

    Other antidepressants — Documentation of analgesic effects with more serotonergically responsive antidepressants is less established than with those whose principal action is directed toward both norepinephrine and serotonin or norepinephrine only. However, agents with a high degree of noradrenergic activity may not be well tolerated, especially in the elderly, because of their association with autonomic, cardiac, and ocular side effects. Other patients whose pain has remained refractory to one or more trials of the TCAs or who have experienced accompanying increased appetite and weight gain, sedation, confusion or cognitive impairment, intolerable dry mouth, or uncontrollable perspiring may find that Selective Serotonin Reuptake Inhibitors (SSRIs) are effective adjunctive agents in the pharmacology of pain management.

    The mechanism of analgesia with SSRIs is less well documented and less well understood than with the TCAs, but may be associated with the primary relief of depression, especially in somatically-expressive instances of depression. Such cases, sometimes formerly referred to as "masked" depression, may be characterized by the patient's tendency to deny or minimize sad mood and dysphoric ideation, while mobilizing somatization as a defense against depression. In many of these patients, effective treatment of the primary depression can ameliorate or even resolve the complaint of chronic pain. In other patients, for whom the symptoms of depression are a complicating feature and sometimes natural sequel to life with chronic pain, favorable response to an SSRI will greatly relieve the subjective experience of distress and, therefore, the affective and emotional intensity with which physical pain is experienced.

    The serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine may also be useful in the treatment of chronic pain. As an example, a randomized trial of venlafaxine in patients with painful polyneuropathy found that venlafaxine was superior to placebo and was similar in efficacy to imipramine [24].

    ADJUNCTIVE THERAPIES
    — Adjunctive therapies encompass a wide array of treatments which may be grouped into the physical interventions, including physical therapy, acupuncture, chiropractic manipulation, massage, and others, and the psychoeducational interventions such as cognitive-behavioral therapy, family therapy, patient education, and psychotherapy. Many patients view these approaches with a sense of skepticism, believing them not to be helpful or appropriate to their circumstances. However, more patients are beginning to embrace them as the media attention these techniques are given increases.
    There is a wealth of anecdotal experience suggesting that when chosen carefully and applied properly, adjunctive therapies enhance the efficacy of pharmacological and interventional therapies. However, data in support of this are lacking. One meta-analysis considering the role of adjunctive therapies in the management of chronic nonmalignant pain reported that the combination of exercise and psychoeducational approaches can lead to a significant reduction in pain and improvement in functional status for a number of musculoskeletal conditions [25]. It was concluded that as chronic pain is a summation of physical and psychological derangements, managing it successfully requires addressing all of its aspects. This begins with making patients aware of what is available therapeutically and explaining what each component therapy offers. There is evidence that combination therapies are more effective than any single approach for maintaining long-term gains. Consideration is also given to the issue of relapse prevention through the integration behavioral work.
    There has been criticism of the multidisciplinary approach as being overly costly and largely ineffective. Here, too, good data are lacking. Part of the problem has to do with the inherent difficulty in measuring improvement. Return-to-work has been considered a useful measure of efficacy of treatment due to its relative objectivity and its relevance. One group published a review and meta-analysis of the literature on the efficacy of nonsurgical, multidisciplinary treatment of chronic pain, focusing upon the "return to work" outcome variable [26]. Despite the study's acknowledged flaws, they demonstrated:

    ·A clear trend in the proportion of patients returning to work (20 to 54 percent)

    ·That the improvement was due to treatment

    ·That benefits were not temporary (follow-up ranged from 1 to 60 months).

    REFERENCES
    1. McCormack, K. Non-steriodal anti-inflammatory drugs and spinal nociceptive processing. Pain 1994; 59:9.
    2. Stuart, JJ, Pisko, EJ. Choline magnesium trisalicylate does not impair platelet aggregation. Pharmatherapeutica 1981; 2:547.
    3. Ballantyne, JC, Mao, J. Opioid therapy for chronic pain. N Engl J Med 2003; 349:1943.
    4. Portenoy, RK. Opioid therapy for chronic nonmalignant pain: A review of the critical issues. J Pain Symptom Manage 1996; 11:203.
    5. Rowbotham, MC, Twilling, L, Davies, PS, et al. Oral opioid therapy for chronic peripheral and central neuropathic pain. N Engl J Med 2003; 348:1223.
    6. Foley, KM. Opioids and chronic neuropathic pain. N Engl J Med 2003; 348:1279.
    7. Eisenberg, E, McNicol, ED, Carr, DB. Efficacy and safety of opioid agonists in the treatment ofneuropathic pain of nonmalignant origin. JAMA 2005; 293:3043.
    8. Joranson, DE, Ryan, KM, Gilson, AM, Dahl, JL. Trends in medical use and abuse of opioid analgesics. JAMA 2000; 283:1710.
    9. Portenoy, RK. Chronic opioid therapy in nonmalignant pain: From models to practice. APS Journal 1992; 1:258.
    10. Portenoy, RK. Opioid therapy for chronic nonmalignant pain: Current status. In: Fields, HL, Liebeskind, JC, eds. Progress in pain research and management, vol I. Pharmacologic approaches to the treatment of chronic pain: new concepts and critical issues. Seattle: IASP Publications 1994; 247.
    11. Allan, L, Hays, H, Jensen, NH, et al. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ 2001; 322:1154.
    12. Allan, L, Richarz, U, Simpson, K, Slappendel, R. Transdermal fentanyl versus sustained release oral morphine in strong-opioid naive patients with chronic low back pain. Spine 2005; 30:2484.
    13. Sabatowski, R, Schwalen, S, Rettig, K, et al. Driving ability under long-term treatment with transdermal fentanyl. J Pain Symptom Manage 2003; 25:38.
    14. World Health Organization. Cancer pain relief. Geneva: World Health Organization, 1990.
    15. Pilowsky, I, Hallett, EC, Bassett, DL, et al. A controlled study of amitriptyline in the treatment of chronic pain. Pain 1982; 14:169.
    16. Jaeschke, R, Adachi, J, Guyatt, G, et al. Clinical usefulness of amitriptyline in fibromyalgia: The results of 23 N-of-1 randomized controlled trials. J Rheumatol 1991; 18:447.
    17. Godfrey, RG. A guide to the understanding and use of tricyclic antidepressants in the overall management of fibromyalgia and other chronic pain syndromes. Arch Intern Med 1996; 156:1047.
    18. Swerdlow, M. Review: Anticonvulsant drugs and chronic pain. Clin Neuropharmacol 1984; 7:51.
    19. Handforth, A, Treiman, DM. Efficacy and tolerance of long-term, high-dose gabapentin: Additional observations. Epilepsia 1994; 35:1032.
    20. www.prialt.com/downloads/product_information.pdf (Accessed 3/7/05).
    21. Ziconotide (Prialt) for chronic pain. Med Lett Drugs Ther 2005; 47:103.
    22. Sharp, D. Novel pain relief via marine snails. Lancet 2005; 366:439.
    23. Staats, PS, Yearwood, T, Charapata, SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA 2004; 291:63.
    24. Sindrup, SH, Bach, FW, Madsen, C, et al. Venlafaxine versus imipramine in painful polyneuropathy: A randomized, controlled trial. Neurology 2003; 60:1284.
    25. Allegrante, JP. The role of adjunctive therapy in the management of nonmalignant pain. Am J Med 1996; 101:33S.
    26. Cutler, RB, Fishbain, DA, Rosomoff, HL, et al. Does non-surgical pain center treatment of chronic pain return patients to work? Spine 1994; 19:643.


    Here are some charts that you might find useful about the opiate receptor types and interactions as well as the various benzo and muscle relaxant meds for pain. -RS
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    1. 3/5,
      great info
      Sep 28, 2007
    2. 3/5,
      Very nice
      Apr 5, 2006
  17. oxalot

    oxalot Newbie

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    I hurt just from sitting here reading all this material!!!!!!!!Time for my meds. Thanks richard smoker. I have read much of this elsewhere also. It does pay to stay informed when one takes chronic meds!
     
  18. melsue420

    melsue420 Silver Member

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    Thank you for the articles. As one with chronic pain, it helps me to know what the doctors are doing to help their patients holistically. I have degenerative disc disease and arthritus affecting my lower back, and have had problems with doctors automatically thinking that I was a "drug-seeker." Due to tolerance issues and my age (27 years old)...I kind of understand why they might assume that about me, but the old addage about assume nothing, it only makes an as$ out of u and me fits here.

    I have had my condition (inherited from my mother's side of the family..grandmother, mother, aunt have/had) for about 10 years. The doctors want to do surgery involving a placing a rod into my back, but I have refused due to lack of money and my aunt is in a wheelchair due to a botched surgery quite like the one the docs want me to get. ~~some of the doctors didn't understand why I didn't want the surgery even after knowing that I PERSONALLY knew someone with the exact condition and the exact surgery...all BOTCHED..she can't even walk now and my aunt's odds of walking again are very slim...so no surgery for me...sorry for ranting..why do they always want to cut people open?

    I have been taking part in a medical study for while now, and the doctors and staff seem more interested and caring...but I am aware it is primarily because I am their lab rat. The study drug is one that combines a synthetic-opioid with an anti-depressant. This combination is something that is awesome for those who have conditions like mine, for the depression that accompanies the chronic pain, the frustration of not bieng able to do normal activities others take for granted(like shaving your legs...playing with your 1 year old son on the floor...putting shoes on), and of course the frustration only makes everything worse because a tense body feels more pain...for me anyway.
    Before swim enrolled in the study, I used to have to look for things to help cope with her pain and associated anxiety, now I don't. Swim told the study doctors everything honestly, as to get the best treatment. I was not judged...at least to her face. They felt sorry and seemed to understand the frustration.

    Other doctors people deal with in everyday life need to learn from these study oriented doctors, not only because it is their JOB to treat patients ethically and fairly, it seems like they would gain more patients that trust them (and vice versa)and more money to pay for their many years of medical school.
     
    1. 3/5,
      good add
      Jan 3, 2008
  19. BobTheGreat

    BobTheGreat Silver Member

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    swim kind of skimmed through the cox2 inhibitor section but the big problem with them is the vascular constriction that leads to strokes and heart attacks.

    I have kyphoscoliosis(one leg is shorther than the other). The left side of the back of your skull contains the parts that control the vital functions of the body. So muscles started twisting swims spine back(like if you step on a small tree it grows with a knot). I have had minor back pain for most of his life but he first really started having constant back pain when he started industrial work(constant manual labor and being on his feet all day must have done him in)

    Anyway I started using 800mg to 1g of ibprofen a few times a day when he was hurting. Eventually he when to his gp who as it turned out was a DO(spine doctor in laymans terms:)). Eventually the ibprofen got too hard on swims stomach so he went to the doc. He assumed opiates were taboo so he started looking online for other ways. He found the cox2 inhibitors or using a nsaid with a proton pump inhibitor. He when to the doc and asked about these but the doc shrugged them off and said hydrocodone would be safer.:cool:

    Unfotunately his back pain has gotten worse and he has to go back to the doc on saturday to see about a different treatment. I am hoping for a low dose of OC but like swiSmoker advised he isnt going the ask directly. He is just going to go with what the doc says. And rightfully so even with all the research I do and his studying toward a degree in pharmocology; his doc still has years more experience and he trusts swim. Hell he was even impressed when swim knew so much about benzos(after going through all the other crap drugs other docs threw at him). sorry about the rambling I am in his insomina half awake/ half asleep stage. Also clonazepam definately helps with the hydrocodone in pain relief and euphoria.
     
  20. godzcamera

    godzcamera Newbie

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    to swim richard smoker. swim loves you this thread is by far the most intresting thread I has yet to read on here. as well with many of the additions to the thread started by You r smoker. thank freeken god swim found this site. I will be dr. swim with all this great knowledge floating around in this forum. thank you!!!