Chronic Pain Medications: Current Trends

for

Legal Nurse Consultants

Chronic Pain, Pain Management, Pain Medications

The International Association for the Study of Pain (IASP) defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage"(Merskey & Bogduk, 1994). According to the biopsychosocial model, pain begins with input from sensory structures, which cognitive processes interpret. Next, individuals respond at a feeling level, then act on their feelings. The progression is sensory  cognitive + affective • illness behavior (Waddell & Turk, 1992). Recent research from the neurosciences is leading to profound changes in the way that chronic pain is conceptualized, researched, and treated. A key finding is the existence of both upgoing and downgoing pain tracks in the brain and spinal cord. Readers are encouraged to review the excellent discussion found at www.medscape.com/viewprogram/ 2170?src=search (Schatzberg & Korn, 2002).

A second key finding is that pain processing structures in the brain and spinal cord can be molded during adulthood (cortical plasticity), a phenomenon once thought impossible (Flor, 2003). These changes appear permanent, both for musculoskeletal (nociceptive) pain patient and neuropathic (nerve) pain patients. Researchers found functional reorganization in both the somatosensory and motor systems. Behavioral interventions can modify cortical plasticity somewhat (Birbaumer, et. al., 1997; Wiech, Preissl & Birbaumer, 2000). Attempts to identify pharmacological agents that prevent or reverse maladaptive cortical reorganization are active areas in current research.

A third key finding is that humeral (blood) changes contribute to the formation and maintenance of chronic pain, occurring as early as the surgeon's first incision (Reuben, 2004). New treatments are available for prevention and palliation, and research moves at a furious pace.

With so much new information, one would think that legal nurse consultants (LNCs) could easily research and address chronic pain medication questions as part of pain damages in litigated cases. Unfortunately, the challenge is often finding the pertinent information and identifying current pain practices. Effective treatments and new

applications are not yet in print, and some may never be (Raziano, 2004a). One factor is that many pain treatments are done off label: legally prescribed but not specifically approved for that use by the Food and Drug Administration.

A common misconception is that off label uses or treatments mean physicians have breached some standard of care. Off label pain treatments are commonly accepted in professional pain circles. A 30 day outpatient headache clinic study found 47% off label drug use (Loder & Biondi, 2004). Most neuropathic pain treatment is off label (James, 2003), and off‑label use may even be evidence based (Dworkin, R., et. al., 2003). A 2 week study of inpatient pediatric pain treatment found 33% off label drug use (Conry & Peden, 2001). An unusual off label pain treatment for intractable discogenic pain is perispinal administration of etanercept, a biological inhibitor of tumor necrosis factor alpha (Tobinick, E. & Britschgi‑Davoodifar, S., 2003). Off‑label pain treatments and uses are so commonly accepted that they do not result in raging debates at professional pain meetings, where almost any current topic may spur raging debate.

The purposes of this article are to discuss current trends in pain medication management, such that LNCs become more familiar with current pain therapies, and to provide brief bibliographic references. This article will review classes of drugs, common pain treatment uses, novel approaches still in the pipeline, and, very briefly, nonmedication strategies that can improve the efficacy of medications.

Drug Therapy

Drug therapy is indicated when the pain condition is substantial enough to affect the patient's quality of life and cannot be treated adequately by physical therapy or similar physical interventions alone (Supernaw, 2002). Medications that work very well for acute or short term use may not work well for chronic use, and may even serve to exacerbate or perpetuate pain complaints. (Raziano, 2004a; Rizor, 2004; Simone, 2004). Once initiated, drug therapy is usually lifetime and can result in significant costs. Chronic pain patients often do not have adequate treatment plans, especially those treated by acute care providers (e.g., surgeons). A sound chronic pain treatment plan must be addressed before damages presented at trial can be adequately assessed. Pain case management may be necessary before legal nurse consultants can get a clear picture of future treatment needs.

Medication selection for specific pain conditions is beyond the scope of this article. The author encourages LNCs to review the excellent treatment algorithm presented at www.medscape.comMewarticle/441743 9 (Gallagher, 2002). Another excellent medication review article may be found at www.hospitalphysician.com/pdf/hp augO2 principles.pdf (Supernaw, 2002).

Antidepressants are excellent drugs for use in chronic pain, and pain physicians have employed them for many years. Until August 2004, however, no antidepressant had formal approval for any chronic pain treatment from the Food and Drug Administration (FDA). In August 2004, Cymbalta° (duloxetine) received FDA approval for painful diabetic neuropathy, but no other chronic pain conditions (Latner, 2004).

The negative impact of anger, anxiety, and depression on chronic pain management is well known and widely reported in the literature (Price & Harkins, 1992), and theorists once believed pain was a variant of depression (Hendler, 1990). Although researchers have not yet shown such a unitary psychological profile (Turk & Melzack, 1992), the links between somatic (physical) symptoms and depression appear strong. Dysregulation of serotonin and norepinephrine may be the biochemical links (Greden, 2003; Montano, 2003), and dopamine may also be a culprit (Barkin & Barkin, 2001). In ways that researchers do not yet fully understand, antidepressants seem to modulate the pain signal in the brain, perhaps by acting on serotonin, dopamine, and/or norepinephrine receptors.

Current pain practice includes tricyclic antidepressants (TCAs, and the newer selective serotonin reuptake inhibitors (SSRIs) and dual serotonin norepinephrine (SNRI) antidepressants; dopamine agents also have utility. The old monoamine oxidase inhibitors (MAOIs) are not currently used, largely because of management complexities. High side effect profiles, and risks of drug to drug or drug to food interactions make MAOIs impractical, especially when several other good choices exist. TCAs have long been the drugs of choice for opioid‑insensitive pain syndromes such as neuropathic pain.

Patients who perceive depression, anger, or anxiety as pejorative labels will often try antidepressants when the drugs are presented as a pain signal modulator. Once they experience results with an antidepressant, patients usually want to continue because the perceived benefits easily overcome pejorative labels. Seven broad classes of antidepressants are:

Current antidepressants commonly used in pain clinics include Lexapro" (escitalopram), Effexor° (venlafaxin), and WellbutrinO (buproprion). Cymbalta©, a similar antidepressant to Effexor©, reports pain reductions in female patients with fibromyalgia (Arnold, et. al., 2004). FDA approval for painful diabetic neuropathy may cause Cymbaltao to become first line treatment for other neuropathies. Lexapro°, a subsequent generation SSRI, is the single isomer of the (slightly) older drug Celexa° (citalopram). Single isomer antidepressants have a lower side‑effect profile with equivalent treatment efficacy and are probably the direction of future research. Etexor© and Cymbalta° act on both serotonin and norepinephrine (SNRI); Effexor also acts on dopamine receptors at higher doses. Wellbutnn© acts on dopamine and norepinephrine receptors, with lower side effects than older TCAs (Barkin & Barkin, 2001). Lexapro©, Effexor© and Cymbalta© may not be used simultaneously, but each can be used concurrently with Wellbutrin©. Lexapro® has faster onset and a cleaner side‑effect profile, Effexor° has more research on its positive effects on somatic disturbance, Cymbalta© seems to help female, but not male, fibromyalgia patients for reasons that are not clear, and Wellbutnn© is excellent for the weepy chronic pain patient. Wellbutrin° may help counteract sexual sideeffects of SSRIs.

A common treatment strategy is to start either Lexapro© or Effexor©, titrate to maximum doses, and allow 6 or 8 weeks for an adequate trial. When a patient gets no results in 8 weeks, the usual strategy is to switch to the other drug. When the patient gets results but not enough relief, a common strategy is to augment the SSRI or SNRI with Wellbutrin©. Observationally, starting antidepressants several weeks before functional improvement ("work hardening") programs can dramatically improve physical outcomes.

As a practical matter, the best antidepressant is the one the patient will take. Patients who feel they are doing well with older antidepressants may not want to change drugs. Most pain patients will be on antidepressant therapy at least a year and some will require lifetime treatment. After the first year, the only sure way to tell whether a patient can discontinue antidepressants is for physicians to titrate the medications down, watch the patient carefully, and make appropriate changes.

Severely Depressed Patients. Treatment refractory depression, when all else has failed, may respond to Zyprexa°, an atypical antipsychotic, or the newer combination drug Symbyax°, which combines Zyprexa° with Prozac©. Zyprexa° and Symbyax° are not first‑line treatments for depression, but have tremendous utility for treatmentrefractory chronic pain patients, for reasons we will discuss in a later section.

Antidepressants and Anxiety. The neurobiology of anxiety is not as well researched as that of depression. Besides the obvious effect of lessening depression, SSRIs are also the current drugs of choice for anxiety (Andrews, 2004). Although observationally, one angry anxious patient significantly improved her behavior with Effexor© and group patient education, research literature is sparse on anger and SSRls/SNRIs. Benzodiazepines were the traditional choice for medicating acute anxiety, but these drugs are not good for chronic use because of dose escalation, inhibition of activity levels, and the potential for abuse and habituation (Raziano, 2004a; Rizor, 2004; Simone, 2004). Two antidepressants, Lexapro® and Effexor©, have FDA approval for Generalized Anxiety Disorder, and both may help anxious pain patients. Lexapro° works a few days faster, and with some extremely anxious patients, time can be a crucial factor. Around 8 weeks, treatment results even out, and both are excellent drugs.

Antidepressants and Sleep. Sleep disturbance is a chronic problem for many pain patients, both sleep onset and early awakening. Sleep deprivation, by itself, can cause pain in otherwise healthy people, exacerbating and perpetuating chronic pain complaints. Sleep medications should be addressed as part of pain damages. Benzodiazepines and hypnotic drugs may be helpful for a few days (14 days or less), but are not generally useful for chronic administration. A subset of pain patients may benefit from Ambien® or Sonata® for occasional use. Both are hypnotics with lower side effect profiles than the older hypnotics.

Patients should avoid SSRIs at night because they can cause insomnia if taken too late in the day or at bedtime. In contrast, the older antidepressant drugs had often limited utility as antidepressants because drowsiness was such a pesky side effect. Older antidepressants make wonderful sleeping aids for chronic use and should be included in pain damages. Trazadone is a serotonin agonist, a drug that triggers a reaction from a cell or hormone, and works very well as a firstline sleep agent, when taken in low doses at bedtime. Trazadone is well tolerated in low doses and can be used chronically without serious risks of abuse, accelerating doses,

or habituation common to benzodiazepines and older hypnotics. Amitriptyline is a tricyclic antidepressant, another older drug that works well in low doses for sleep; amitriptyline also has utility for reducing pain intensity in neuropathic pain. Remeron©, taken in low doses at bedtime, is a secondgeneration SSRI that seems to have a stronger sleep action than either Trazadone or amitriptyline, and should probably be used as a second‑line sleep agent after Trazadone or amitriptyline have failed. Patients taking therapeutic doses of newer SSRIs or SNRIs can use either trazadone or Remeron° in low doses at night. Once started, a patient will probably need low dose antidepressants for sleep on a daily basis, to lifetime.

Nonsteroidal anti inflammatories (NSAIDs) date from the ancient Greeks and Romans, who used willow bark, a natural source of salicylic acid (aspirin). An excellent discussion and review of NSAIDs, including doses and dosing schedules can be found at www.hospitalphysician.com/ pdf/hp aug02 principles.pdf (Supernaw, 2002). These drugs treat any painful condition with an inflammatory component, especially arthritis or rheumatic diseases. NSAIDs are both primary prevention drugs and acute treatment for migraine. The mechanism of action is to inhibit cyclooxygenase, a biological component of inflammation. Researchers have identified at least three COX enzymes, with evidence pointing toward more, so even more specific NSAIDs are in the research pipeline. Although both physicians and pain patients tend to overlook NSAIDs, NSAIDs have significant utility for chronic use (Raziano, 2004a).

Older NSAIDs may be useful for patients with limited funds. Used with appropriate precautions (food or milk), older NSAIDs are reasonably manageable when no other good choices exist. Nevertheless, the optimum treatments are the newer NSAIDs, cyclo oxygenase 2 (COX2) inhibitors. COX2s reduce incidences of gastric distress, the major sideeffect of NSAIDs, though none are perfectly side‑effect free. The two available COX2s are Bextra® and Celebrex°. Mobic® and Lodine© act much like COX2s but do not have the correctly shaped molecule to meet the definition; technically, Mobic© and Lodine© are COXl sparring. Vioxx.© was recently removed from the market by its manufacturer, on their own volition. Coxibs (COX2s) still in the research pipeline include parecoxib, etoricoxib, and lumaricoxib (Stichtenoth & Frolich, 2003). Once instituted for chronic pain, patients will probably use NSAIDs daily, to lifetime.

As mentioned, the primary complication of NSAIDs is gastric distress. However, a subset of patients will experience rebound pain from NSAIDs, greatly restricting NSAIDs' utility for these patients. Rebound pain occurs when the patient becomes habituated to painkillers that are not ordinarily habituating; instead of the drug treating the patient's pain, absence of the drug causes the patient's pain, often as headache. Rebound pain may occur with over the counter preparations such as aspirin, acetaminophen, and non prescription strength ibuprofen or naproxin. Current medical research cannot predict which patients will rebound. Once rebound pain occurs, the patient is at risk for future rebound pain to lifetime. Some physicians believe that the best management course for rebound patients is to provide asneeded NSAIDs for use in pain flare ups, but no more than two weeks at a time, and weeks or months between courses of treatment. Other physicians believe that rebound precludes use of NSAIDs. After clarifying the patient's status with treating physicians, pain damages should include asneeded NSAID use with rebound patients. One should not assume that patients successfully using daily NSAIDs will suffer rebound.

NSAIDs and Preemptive Analgesia. Anesthesiologists have long used ketamine, an n‑methyl‑d‑aspartate (NMDA)inhibitor, to prevent the brain from processing and interpreting pain signals during surgery. Without NMDAinhibitors, surgical patients are unconscious but their brains continue to read and store pain signals, a process many researchers believe predisposes later development of chronic pain.

I lowever, protecting the brain is not enough. Preventing the humeral (blood) system from starting the inflammatory cascade is also key to preventing chronic pain. Surgeons typically tell patients to stop all NSAIDs before surgery because the older N,SAIDs prevent blood clotting. However, the COX 2 NSAIDs do not prevent blood clotting and may be used for preemptive analgesia of postsurgical pain. Patients who received COX 2 NSAIDs within 24 hours before surgery had less pain and used fewer opioids postsurgically (Fenton, Keating & Wagstaff, 2004). Parecoxib, an mjectable form of Bextra°, is in the research pipeline, and will permit administration just before surgery. Peri operative administration of NSAIDs does not work as well because the inflammatory cascade starts with the first surgical incision (Reuben, 2004). Preemptive analgesia is a major step toward primary prevention of chronic pain, and pain damages should include these costs for any proposed surgery.

Antiseizure (neuroleptic) drugs are excellent choices for neuropathic pain, trigeminal neuralgia, migraine prevention, diabetic neuropathy, postherpetic neuralgia, nerve injuries, and other opioid insensitive pain syndromes. Patients may report pain reductions within 48 hours. Common neuroleptic drugs are carbamazepine (Tegretol°), gabapentin (Neurontin©), lamotrigine (Lamictal°), zonisimide (Zonogran°), topiramate (Topamax°) and tiagabinet (Gabitril°). Used less often and best reserved for use after treatment failures with other neuroleptics are phenytoin (Dilantin°) and valproic acid (Depakenel") (Supernaw, 2002).

Neuropathic pain patients tend to experience better relief

with antiseizure drugs than they do with opioids. The exact mechanisms of the drugs are unknown. Observationally, pain patients either love neuroleptic drugs or hate them because of side effects. Lower doses may not work and patients must reach peak doses before deciding that a neuroleptic drug does not help. When patients do not respond at peak doses of one neuroleptic, systematically titrate other neuroleptics to peak doses before abandoning this class of drugs. Like many treatments in pain management, drugs that work for one patient may not work for another; trial‑and‑error is inherent in pain management. If carbamazepine (Tegretol°) is the neuroleptic of choice, then damages must also include regular lab work.

Older antipsychotic drugs have no utility in chronic pain management because the side‑effect profile outweighs the benefit, primarily tardive dyskinesia, an abnormal movement syndrome that may be irreversible. An intriguing class of drugs for pain management are the atypical antipsychotics. While not side effect free, atypicils are less likely to cause tardive dyskinesia. Use of atypical antipsychotics requires patient preparation and education. Patients (or professionals) who read the package inserts without knowing their use in pain management become justifiably confused. As the name implies, atypical antipsychotics treat schizophrenia and other psychotic disorders. Olanzepine (ZyprexaO) and quetiapine fumarate (Seroquel°) have gained FDA‑approval for bipolar mania, with fewer side effects than the older antipsychotics. Their exact mechanisms of action are unknown, but both are dopamine and serotonin antagonists, which block or nullify the action, which may play roles.

Both drugs work very well for extremely difficult to treat pain patients. These patients typically have some combination of treatment resistant depression, bipolar disorder, and/or severe sleep disturbance. Patients whose pain medications have reached maximum doses but who continue to crave narcotics, seem to especially benefit. With the most complex pain patients, atypical antipsychotics may help when all else fails (Hall, 2004). Besides psychiatric rehabilitation and chronic pain management, Zyprexa° and Seroquel° have proven useful for drug rehabilitation centers and posttraumatic stress disorder clinics. Side effects seem to be weight gain and metabolic slowing, though a raging debate is currently ongoing about the connection between atypical antipsychotics and diabetes. The treatment gains so thoroughly outweigh the risks for intractable patients that the author would not hesitate to recommend atypical antipsychotics for the most difficult patients.

In contrast with SSRls, atypical antipsychotics should be used at bedtime. Many patients experience somnolence, and this side effect can be used to their benefit. Patients who complain of sleeping no more than two or three hours nightly gain sound sleep with atypical antipsychotics. The extra sleep when first taking the drugs is both common and beneficial, but decreases to more normal levels after the first few days. For purposes of calculating pain damages, once treatment starts, patients can expect to use atypical antipsychotics daily, to lifetime. Pain damages should also take into account dietitian assistance for atypical antipsychotic patients for weight gain and metabolic slowing.

Opioids' primary function is analgesia, or pain relief Useful opioids for pain management are pure agonists of the opioid rnu receptor in the brain. Examples include codeine, oxycodone, hydrocodone, fentanyl, dilaudid, and the opioid gold standard, morphine. Opioids are always federallyregulated, scheduled drugs, Schedule 11 or Schedule 111. .

Chronic use of opioids can be problematic for reasons that include legal, criminal, sociocultural, and medication sideeffects, detailed discussions of which are beyond the scope of this article. No topic in chronic pain management is more emotionally loaded than discussion of opioids. To gain a more clear view of this very complex picture, the author encourages legal professionals to read the position statement of the American Academy of Pain Medicine and the American Pain Society, also adopted by the American Academy of Pain Management. The opio d position statement can be found at vvww.anipaitisoc.org/advocacv/()plolds.littii.

Legal professionals rarely make treatment decisions about opioids but must be aware of the issues. Pain damages that include opioid medications invariably raise questions about appropriateness,. addiction, abuse, habituation, dose escalation, diversion, and complications. Detailed discussion could be the subject of another article.

Opioids arc excellent drugs for acute pain such as postsurgical pain or for acute pain flares. A subset of pain patients benefits from chronic opioid management. In contrast, another subset is recovering persons with pain who should never attempt chronic opioid therapy. Few pain patients find that opioids, alone, address their complaints, and many pain patients fare better taking drugs more suited to chronic use. Rational poly pharmacy may include both opioid and non opioid medications. For our discussion, we will divide opioids into short acting, long acting, and novel delivery systems.

Short‑Acting Opioids. Short acting opioids have been around since the Greeks and Romans used poppy juice for pain relief. As the name implies, these drugs have fast onset and short half life, typically four to six hours. Short acting opioids typically cause euphoria or somnolence, and some patients mistake euphoria for pain relief. Examples include Lortabsc~, Vicodin©, and Tylenol© #3.

Long Acting Opioids. Long acting opioids first appeared on the market in 1995 with the introduction of Oxvcontin°. For patients requiring chronic opioid management, long acting opioids are excellent choices. These drugs have slow onset, long half‑life up to 72 hours, produce no significant euphoria when used correctly, and greatly improve quality of life for appropriate patients. Despite its utility, Oxvcontin" has produced raging debates, even litigation, about diversion, addiction, and abuse. To address this problem, in May 2004 Oxvcontin's manufacturer formed a manufacturing alliance to explore abuse‑resistant tednlologry (Will, 2004).

Other long acting opioids include lhrraagesic°" (fentanyl) patches, Kadian" (kapanol), and 1VIS Contin (morphine), all discussed below. Methadone is an old drug available in generic forrn that is useful for patients with limited funds, but is not the best opioid treatment alternative available. Blood levels can vary widely with the same dose and methadone does not provide the comfort level of the newer long acting opioids. However, methadone is the most inexpensive alternative ti>r nociceptive pain when other drugs have failed.

Novel Delivery Systems. The hot debate about diversion, abuse, and criminal concerns has generated intense research for novel delivery systems that reduce diversion and abuse. Human nature being what it is, no drug deliver  system is foolproof. Documented cases of entrepreneurial uses of novel drug delivery svsterns arc already appearing. However, novel drug deliver', systems may slow diversion.

Duragesic" patches are one such novel delivery system. The medication is stored in gel form in a protected reservoir, then released slowly through an absorption rnembrane. ]'he patches release medication over a period of 72 hours. Medication release is so slow that patients report little euphoria.

Kadian"I capsules arc a second novel delivery system for long acting morphine. Administered at 12 hours or 24 hours, time release pellets deliver oral morphine sulfate. Polymer shells enclose the pellets and break down to release the drug in the digestive tract. The opioid cannot be extracted from the polymer casing except in the digestive tract (Kaplan, Milirnan, Kaplan, & Collins, 2004). In theory, the polymer pellets preclude a euphoric dose if crushed.

Actiq° (fentanyl) is a transmucosal delivery system for short acting fentanvl. The drug is released only when swabbed against the mucus membrane inside one's cheek. The transmucosal mechanism delivers a lower dose, if crushed, and in theory, delivers a subeuphoric dose.

Mixed Agonist AntagonistOpioids. Re introduction of mixed agonist antagonist opioids is a recent development in pain management. Mixed agonist antagonist opioids are those that partially target the mu opioid receptor in the brain but also partially block it. Buprenorphine is a mixed agonist antagonist opioid, with trade names including Nubain°, Stadoll", Buprenex°, and Subutex°. A related drug, Suboxone©, combines buprenorphine with naloxone (Narcan°), a pure opioid antagonist used to counteract overdoses. The theory behind Suboxone° is that the antagonist effect of naloxone further reduces chances for euphoria.

Occasionally, one may see mixed agonist antagonist drugs in treatment plans. As pain drugs, mixed agonistantagonist drugs work poorly and rnay be most appropriate for the small subset of pain patients who were substance abusers before their pain started. Mixed agonist antagonists provide some analgesia and arc safer to use when the medical providers treat an unknown patient, as in an Emergency Room visit. Because of their mixed effect, thev are harder to abuse and make diversion less likely. The best use for mixed agonist antagonists is to cushion the detoxification process for substance abusers. Patients on chronic opioid therapy with pure agonist opioids cannot take mixed agonistantagonists because a close of mixed agonist antagonist will trigger withdrawal.

Novel Delivery Systems in the Pipeline. Research continues on a miniature implanted osmotic medication pump delivering sufentanil (Sufenta "), a stronger drug than fetitanyl. The osmotic mini pump is the size of a matchstick implanted under the skin and is designed to deliver medication for 90 days (Fisher, Kellett, & Lenhardt, 2003). Researchers are working on a controlled release version of trainadol (Ultrain") (Tiwari, Murthy, Pal, Nlehta, & Chowdary, 2003). Sublingual buprenorplune is in the research pipeline (Das &.Das, 2003).

Presently, Skclaxin°° (rnetaxalone) is the only available non‑sedating muscle relaxer and is, therefore, the most appropriate choice for chronic use. Older muscle relaxers are fine for acute use, but are sedating, reduce physical activity and blunt feelings. Older muscle relaxers are not appropriate for chronic use.

The best plan is to identify the pain generator causing the chronic muscle spawn, so the patient may not need Skelaxin° daily. However, daily use to lifetime would be acceptable, if that is what works best for the patient.

Beyond general cautions, none of the drugs discussed require laboratory tests except Tegretol". Patients on longterm Tegretol° require quarterly complete blood counts (CBC) (Raziano, 2004b).

Detailed discussion of non medication pain management is beyond the scope of this article. However, optimum pain medication management greatly depends on optimum lifestyle management. Determined pain patients can successfully defeat the best pain medications, if they poorly manage behavioral factors. Immune system function is not purely

biological and, to paraphrase St. Augustine, drugs act on the nature that they find. A flu shot is about as biological an intervention as one can find. Researchers from the University of Wisconsin identified that thinking about positive or negative events in one's life affected how robustly study participants produced antibodies (Fauber, 2003). Although no similar research exists for pain medications, ignoring the implications would be unwise.

Ablative procedures (radiofrequency, etc.) Acupuncture Anesthestic blocks Behavioral Counseling Biofeedback Electrical stimulation technologies (TENS, Alpha‑ Stii muscle stimulators, etc.) Exercise Family therapy Guided irnagen~ Heat Humor Hypnotherapy Ice Implanted technologists (dorsal column stimulators, pain medication pumps) Marriage counseling

Movies Multidisciplinary pain management Occupational therapy Patient education Physical therapy Pool therapy Positive self talk Prayer and spirituality Relaxation Self hypnosis Specialty interventions (rape survivor counseling, Eye Movement Desensitization Reprogramming, etc.) Stress management Twelve‑Step Programs Vocational rehabilitation Volunteer work Work

Thus far, we have confined our discussion to drugs useful for chronic administration. Drugs that may have excellent uses acutely often have little utility for chronic use. Usual problems include tendencies to habituation or abuse, decreased activity levels, need to escalate doses, and potential for diversion. Such drugs include benzodiazepines, most muscle relaxers, shortacting opioids (except sparingly for breakthrough pain), hypnotics, and mixed agonist antagonist opioids (except a small subset of patients). A suggested chronic pain drug formulary is included in Table 1, and classes of drugs to avoid are listed in Table 2 (both on the following page).

Chronic pain cannot be treated the same as acute pain. Many treatments that are perfectly appropriate for acute pain do not help chronic pain and may make it worse. Once pain becomes chronic, most patients require daily medication, and rational polypharmacy is the treatment approach of choice. The goals of chronic pain management are to increase function and daily activity, and by doing so, help patients gain better pain control. Even those patients who do not gain lower pain levels can often gain better quality of life through increased activity.

When reviewing pain cases, LNCs should start with the usual search techniques. After exhausting those, LNCs may require review assistance from experts skilled in multidisciplinary pain management. Pain management may be evidence‑based, even when done off label, but sometimes anecdotal accounts may be the only proof.

LNCs should remember that pain case analysis and management may be necessary before damages can be adequately quantified. This is especially true when patients have been treated mostly by surgeons or by single‑discipline ("needle clinics") pain treatment centers.

Pain diagnostics is a young science, and all pain centers are not created equal. Indeed, some approaches are considerably less equal than others (with apologies to George Orwell).

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