Pain Management

Is it the Pain or the Hurt that Matters

Equivalency

Opioid Agonist IM/IV/SQ Oral Conversion Factor Half Life Starting DoseMorphine 10 30 3 2-3 hours 5 mg IV Q 4 Controlled Release Morphine (MS Contin) – 30 – 15 mg PO Q12 Codeine 130 200 NR 1.5 Hydromorphone (Dilaudid) 1.5 7.5 5 1 mg IV Q4 Levorphanol (Levo-Dromoran) 2 4 2 Methadone (Dolophine) 10 20 2 Meperidine (Demerol) 75 300 NR 4 Don’t Hydrocodone (Lorcet, Lortab,Vicodin, others) N/A 30 N/A 10 mg PO Q3-4 Oxymorphone (Numorphan) 1 (10 rectal) N/A Fentanyl 100ug/hr N/A N/A Fentanyl Patch 0.1 – 25 mcg/hr=50 mg Morphine PO Q24hrs Controlled Release Oxycodone (Oxycontin) – 20 – 10 mg PO Q12 Oxycodone (Percocet, Tylox) N/A 20 N/A 5 mg PO Q4 Propoxyphene — ?NR N/A Methadone 1-10 2-20   hydomorphone 1.5 mg = 10 mg morphine (10-20 minutes peak for hydro and morph) Br J Anesth 1984;56(8):813)  

Oxycodone and Hydrocodone

no difference in pain control between hydrocodone 5 mg and oxycodone 5 mg (Acad Emerg Med 2005;12(4):282)  

Hydromorphone

0.015 mg/kg of dilaudad was equivalent to 0.1 mg/kg   Rapid titration using 1+1 protocol. Use 1mg initially and an additional 1mg in 15 minutes (Ann Emerg Med 2009;54:221) and (54:561)

Morphine

  Oral Morphine per day/2 = fentanyl patch per hour   Give 10% of 24 hour dose for breakthrough   Give everyone colace (softens), senna 2 tabs Qhs (stimulant), lactulose (large sugar)   IV opioids take 8 minutes, Oral 60-120 minutes, SC 20-30 minutes   Increasing dose, mild to moderate 25-50% Severe 50-100%   Rescue dose 20%   works at the μ receptors 90% metab by liver conjugation contains Sodium Bisulfate which may cause allergic reactions histamine release may cause appearance of reactions     Dilaudad Toradol-no advantage over PO Fentanyl Nubain Ultram   Just b/c one opioid doesn’t work does not mean another one in same class will not, start at 50% of prior dose with new med.   Life Sci. 2000;66(23):2221-31 > Lung opioid receptors: pharmacology and possible target for nebulized > morphine in dyspnea. > Zebraski SE, Kochenash SM, Raffa RB.   Chronic pain actually forms neuronal connections between somatic and pain sensory fibers causing pain with normal sensations= allodynia . Can also cause mood changes, depression, insomnia   12 hrs for fentanyl patch to work. warm temp allows more in, cold less.   Oxycontin gives a surge dose then the rest is time released.   Methadone’s analgesia lasts 6 hours.   Do not use NSAIDS unless no worry at all for GI Bleed   Instead use Bextra, as effective as Vioxx but without the side effects. Only worry in patients with renal failure (Audio Digest Chronic Pain) Can give 20 mg BID for 5 days and then 10 mg BID.

Codeine

The answer, it would seem, lies in the fact that there is highly variable expression in the brain of the gene to produce cytochrome P450 2D6 55. There appears to be moderate ethnic variability, with the most ‘non-converters’ being in whites. In this group, up to 10% are non-converters and up to another 10% are poor metabolizers 56. With Asians, only 1% are non-converters. This means to me that current studies suffer from the fact that there has not been an effort to look at how well this drug works in known converters. Taking the population as a whole, up to 20% can be expected to have diminished or no analgesic effects. Eliminating 1 in 5 people would significantly skew the results. I am still awaiting a study on codeine that takes this into account. I may still be convinced that it is a poor drug. Until then, I think it makes sense to NOT prescribe codeine as an unknown – i.e. for someone new to narcotic pain relief. This both because of the studies such as mentioned and because there is a finite chance (10-20%) the patient will be a non-converter. On the other hand, it is probably medical myth to assume it never works. With the occasional patient that requests it, and has felt it worked in the past, it is reasonable to use. (RaneyFacts) 5% expressed poorly 5% not expressed at all p450 enzyme needed to metab codeine to morphine   These studies also suggestthat the analgesic effect of codeine is either wholly or mostlydependent on its metabolism to morphine.6 7 Metabolismof codeine to morphine is catalysed by the cytochrome P450 enzyme CYP2D6. Over 50 different genetic variants are known to existfor CYP2D6, which leads to a wide spectrum of metabolic capabilities within populations.8 9 Individuals are normally classified as either poor metabolizers (PM) or extensive metabolizers (EM), depending on the activity of the enzyme, although this is knownto be an oversimplification. PMs will produce little or no morphinefrom codeine whereas EMs will produce morphine, although theactual amount may show wide variation.10–12  

Back Pain

Robaxin Take 1500 mg Q2hrs as long as no cognitive deficits as loading dose, then switch to the 1000 mg-1500mg QID. Do not use generic, it is not as good. If there is an inflammatory process, you need NSAIDs as well.   Use gabapentin for all of neuropathic pain. Worry about it only in renal patients. it does not affect drug levels.   Use Ultram instead of opioids for acute and chronic pain   Actin is the Fentanyl citrate lollipop Works very rapidly   Demerol’s metabolite normperidine causes seizures and highs.   Myofascial pain: true trigger points cause pain elsewhere when pressed. Travel lists the triggers. Reflex Sympathetic Dystrophy (RSD): calcitonin 200 IU IN OD, it takes a few days to work   Fentanyl Infusion at 2/3 bolus dose/hour     Analgesic adjuvants to opioids • Anesthesiology 1999: 0.5 mg/kg ketamine PO q12h – Decreased need for breakthrough oral opioids, less somnolence • J Pain and Symptom Management 1999 – 0.1 – 0.2 mg/kg/hr infusion ketamine in terminal patients relieved pain morphine could not   Acute Pain Management in Trauma Give fentanyl bolus until relief then start drip at 2/3 required dose per hour   Patient activated transdermal patches as good as IV PCA (JAMA 3/16/04)    

Demorol

normeperedine can last up to 40 hrs in the elderly ——————————————————————————– Ketamine for Perioperative Pain Management (Anesthesiology Volume 102(1) January 2005 pp 211-220)  

Opioid induced constipation

  Neuropathic Pain Use opioid and gabapentin in combination ( NEJM Volume 352:1324-1334 March 31, 2005 Number 13)     Use ketamine for the RSI and then keep it going for pain control 0.1 mg/kg infusion   Topical anesthesia for all ng tubes 5 cc of lidocaine jelly 5 minutes before procedure   Intradermal lidocaine for IV starts   It is PROCEDURAL SEDATION, not conscious sedation Titrate analgesia and then sedation Even if you use incredibly potent sedative, patients still need pain control because pain is a spinal reflex and patients will have greater post-procedural pain. Pain is inducible   Best way to break spasm, like in lower back pain, is to stop the pain. Just keep titrating the opioids until pain is stopped. Then they must be treated with lower doses for 24-36 hours   NSAIDS require induction of Cox-2 receptors and give no relief in the first few hours   Canabinoid Canabinoid receptors receptors CB1 receptor stimulation produces receptor stimulation produces two effects: Analgesia Addictive behavior NOT endorphin sites that lead to addiction, only dependence   Methylnaltrexone Methylnaltrexone (MNTX) (MNTX) n No central antagonism No central antagonism – does not cross BBB does not cross BBB n Well absorbed PO Well absorbed PO n Alvimopan Alvimopan n Mu Mu selective antagonist selective antagonist n Minimal intestinal absorption Minimal intestinal absorption Bates 2004 Alvimopan Alvimopan 6 mg bid PO 6 mg bid PO n Shorter bowel recovery time, 1 day earlier discharge Alvimopan Alvimopan 6 mg pre 6 mg pre-op decreased post op decreased post-op op N&V from 23% to NONE N&V from 23% to NONE Taguchi 2001   NSAIDs NSAIDs n Can act as analgesic only if Can act as analgesic only if arachadonic arachadonic acid / acid / prostaglandin cascade activated prostaglandin cascade activated n Not effective in neuropathic pain Not effective in neuropathic pain – no tissue injury no tissue injury or inflammation or inflammation n Osteoarthritis good example of no inflammation, Osteoarthritis good example of no inflammation, little effect little effect n Requires 4 Requires 4-6 hours for blood 6 hours for blood-borne mediators to borne mediators to induce COX induce COX-2 receptors in dorsal horn 2 receptors in dorsal horn – cannot cannot obtain relief from obtain relief from NSAIDs NSAIDs in first few hours. Renal colic in majority of cases caused by raised intra intra-mural tension mural tension n NSAID will decrease that tension, requires 15 NSAID will decrease that tension, requires 15-20 20 minutes minutes n NOT effective in 15 NOT effective in 15-30% of patients as pain induced 30% of patients as pain induced by other mechanisms by other mechanisms n Note that pain control due to direct impact on mural Note that pain control due to direct impact on mural stretch receptors, so does not require COX stretch receptors, so does not require COX-2 induction induction   ACUTE PAIN MANAGEMENT IN THE EMERGENCY DEPARTMENT James Ducharme MD CM, FRCP Dalhousie University, Department of Emergency Medicine Saint John Regional Hospital Reference List · Johnston CC, Gagnon AJ, Fullerton L, Common C, Ladores, Forlini S. One-week survey of pain intensity on admission to and discharge from the emergency department: a pilot study. Journal of Emergency Medicine 1998; 16(3):377-382. · Unruh AM, Ritchie J, Merskey H. Does gender affect appraisal of pain and pain coping strategies? Clinical Journal of Pain 1999; 15(1):31-40. · Raftery KA, Smith-Coggins R, Chen AHM. Gender-associated differences in Emergency Department pain management. Ann Emerg Med 1995; 26:414-421. · Kelly AM. Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? Academic Emergency Medicine 1998; 5(11):1086-1090. · Horgas AL, Tsai PF. Analgesic drug prescription and use in cognitively impaired nursing home residents. Nursing Research 1998; 47(4):235-242. · Acute pain management guideline panel. Acute pain management: Operative or medical procedures and trauma, Clinical Practice Guidleine No 1. Publication No. 920032. 1992. Rockville, Md, U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. Ref Type: Report · Singer AJ, Richman PB, Kowalska A, Thode HC, Jr. Comparison of patient and practitioner assessments of pain from commonly performed emergency department procedures. Annals of Emergency Medicine 1999; 33(6):652-658. · Todd KH, Funk JP. The minimum clinically important difference in physicianassigned visual analog pain scores. Academic Emergency Medicine 1996; 3(2):142-146. · Ducharme J, Beveridge RC, Lee JS, Beaulieu S. Emergency management of migraine: is the headache really over? Academic Emergency Medicine 1998; 5(9):899-905.     PAIN: OF COURSE IT’S ALL IN YOUR HEAD NEUROBIOLOGY OF PAIN DEFINITION   IASP: “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. Even the authors were aware of this definition’s inadequacy, and hastened to add: “Pain is always subjective… This definition avoids tying pain to the stimulus”. Despite the disclaimer, this definition DOES tie the sensation to the stimulus, perpetuating the centuries old fallacy. It does not, and cannot, explain many of the perplexing aspects of pain experience, and it does not consider the crucial influence of the brain on the sensation and the perception of pain.

1. The brain can generate pain, create a perceptual experience, independent of the peripheral input, i.e., regardless of the presence or the extent of tissue damage or pathology.
2. The brain is continually modified by experience and sensory input.

THE PUZZLE OF PAIN   Without the contributions of modern neuroscience, it is impossible to unravel the multitude of the pain puzzles:

1. Well known instances of NO PAIN with major injuries
2. Excruciating PAIN in missing structures (phantom pains), or denervated structures (below spinal cord section in paraplegics)
3. PAIN persisting, after complete healing of injury
4. PAIN provoked by touch, or no stimulus at all
5. PAIN that is delayed, or non-anatomically spread

NOCICEPTION AND PAIN PATHWAYS   Stimuli from the periphery (mechanical, chemical, thermal) are transmitted to the spinal cord through the sensory afferent nerves. Damaged tissue is a source of many amines and peptides that stimulate sensory nerve endings: bradykinin, adrenaline, 5HT, PGE2, IL-1, IL-6, TNF-alpha, etc. These afferents synapse on the dorsal horn second order neurons in the spinal column (projection neurons), which form pathways extending to the brain – primarily thalamus and somato-sensory cortex. Acute, physiological pain is mediated in the spinal synapses mainly by the GLUTAMATE-activated AMPA type of glutamate receptors. In addition to glutamate, excitatory transmitters include AcCh, substance P, and CGRP, while GABA, enkephalin, 5HT and NA provide the inhibitory neurotransmission. NEUROBIOLOGY OF CHRONIC PAIN Chronic pain is not just a prolonged acute pain; it is a distinct entity, with many functional and structural alterations of the peripheral and central nervous system. ERIPHERAL SENSITIZATION – PRIMARY HYPERALGESIA Peripheral nociceptive hyperexcitability is induced through increased receptor (autosensitization) or cell membrane (heterosensitization) reactivity to stimuli, usually sustained presence of inflammatory factors. CENTRAL SENSITIZATION – SECONDARY HYPERALGESIA Central hyperexcitability is the key process in the generation of chronic pain. It is mediated by NMDA-type of post-synaptic glutamate receptors, and it results in transcriptional changes and manufacturing of the c-fos protein (the marker of central sensitization) in the second order dorsal horn projection neurons. Repetitious and intense activation of the high-threshold C-fibers and AMPA post-synaptic receptors results in activation of the NMDA post-synaptic receptors (through dislodging the Mg ions and opening the N and Ca channels to Ca influx) and the NMDA mediated WIND-UP phenomenon (augmented response of the dorsal horn neurons to the same intensity stimuli). Activation of the NMDA-receptors represents the first step in central sensitization, i.e., the transition from acute to chronic pain. Knowing this makes it easy to realize that adequate treatment of physiological, nociceptive pain is the most important goal of acute pain management – prevention of central sensitization! Other changes involved in central sensitization include substance P – NO (nitric oxide) cascade (with expansion of the receptive fields), increased release of NPY, VIP, galanin, and somatostatin from the pre-synaptic C-fiber terminals, hyper-sensitization of the WDR (wide dynamic range) neurons to non-nociceptive stimuli, expression of substance P by A-fiber pre-synaptic terminals, and sprouting of A-fiber terminals into the superficial layers of the dorsal horn (thus synapsing onto the nociceptive second order neurons). Reorganization or remodelling of the synapses at the dorsal horn level, as well as at the brainstem, thalamus, and somatosensory cortex levels, is a well-documented phenomenon, referred to as neuronal plasticity, responsible for a variety of chronic pain syndromes. Central sensitization and neuroplastic remodeling are responsible for all the main features of chronic pain: hypersensitivity to nociceptive stimuli (hyperalgesia), perception of pain upon non-nociceptive stimulation (NNP and allodynia), expansion of the pain-receptive fields and trigger-zones, and delayed pain. Changes in central sensitization can be viewed as:

1. FUNCTIONAL (NEUROCHEMICAL) HYPEREXCITABILITY:Activation of the NMDA- receptors, wind-up, sensitization of WDR neurons, expression of substance P by A-fibers
2. STRUCTURAL (NEUROANATOMICAL) HYPEREXCITABILITY:

Dying-off of C-fiber terminals, sprouting of A-fiber terminals, extensive reorganization of the somatosensory cortical maps, remodeling in the brainstem, cerebellum, basal ganglia, and motor cortical areas. DYSFUNCTIONAL DESCENDING INHIBITION – FAILURE OF INTERNAL ANTINOCICEPTION As illustrated in PAIN PATHWAYS, nociception activates not only the afferent pathways, but also a variety of segmental and descending, inhibitory or anti-nociceptive pathways (SLIDE 5). Increased brainstem CCK, and deficiencies in the descending enkephalin, 5HT, and NA pathways, can all contribute to dysfunctional anti-nociception. Processing of pain at the brain level has profound implications for both, the perception of pain, and for the management of pain. Ascending pain pathways are relayed through the thalamus to the somatosensory cortex, which is responsible for the initial localization and the intensity of the stimulus (SENSORY-DISCRIMINATIVE function), as well as to the limbic brain structures, esp. the anterior cingulated cortex, which is responsible for the unpleasant, aversive aspect of the experience (AFFECTIVE-MOTIVATIONAL function). Both of these areas communicate extensively and reciprocally with the prefrontal cortex, which brings the situational and memory context to the experience (COGNITIVE-EVALUATIVE function). These three aspects of pain experience (R. Melzack’s gate and neuromatrix theory of pain) make a variety of pain treatment modalities potentially helpful, and at the same time provide the neurophysiological and neurostructural explanation of these modalities’ efficacy (dismissing, in the process, all kinds of hogwash that has been written about “psychogenesis” of pain).   CHRONIC PAIN SYNDROMES Chronic pain is generally categorized, according to etiological factors, as stemming from tissue damage – inflammatory pain, or from nerve damage – neuropathic pain. The former is evident in various injuries (low back pain), infections, inflammatory diseases (RA, IBD, SLE) and immune/neuroendocrine dysfunctions (possibly FM/CFS, MPS). The latter is encountered in diabetes, certain infections (shingles), cancer, traumatic nerve injury, and following amputations (limb, breast). Opioids are exceedingly effective in managing inflammatory pain, whereas they are less effective in managing neuropathic pain, due to the loss of pre-synaptic opioid receptors, and the extensive re-wiring of the dorsal horn synaptic circuits. Low back pain In up to 85% of sufferers, there is no detectable damage (“no objectively demonstrable organic pathology”); in only about 15% can one of the five recognizable causes (herniated disc, arthritis, infection, tumor or fracture) be demonstrated. In addition, it is estimated that about 10% of low back pains develop a neuropathic dimension, making the picture even more puzzling. The vast majority of chronic low back pain sufferers continue to be under-treated or maltreated, labeled as “somatizers” or malingerers, despite ample evidence for central sensitization and somatosensory mapping reorganization in such patients. Fibromyalgia and Myofascial Pain Syndrome There is ample evidence in these disorders, as well, of altered central processing of the incoming nociceptive and non-nociceptive stimuli, at both the spinal and the brain level. Incoming stimuli from muscle C-fiber afferents are much more potent inducers of central sensitization than skin afferents, explaining lower pain threshold (hyperalgesia) and pain on movement (proprioceptive allodynia) in these patients. In addition, a dysregulated neuroendocrine stress response (decreased cortisol, growth hormone and IGF-1 secretion) may compound the picture in about a third of patients. Phantom limb pain Phantom pains affect over 70% of amputees, and persist for 2-7 years in about 60% of them; fewer than 15% obtain total pain relief. Extensive somatosensory cortex reorganization, with expansion of the trigger zones, has been demonstrated in numerous brain imaging studies. Peripheral ectopic discharges (from the stump neuroma), deafferentation hyperexcitability, and unmasking of the underlying silent connections, may all be contributory. In addition to phantom limb pain, phantom pains following mastectomy, and phantom body pains below the spinal cord section in paraplegics, are gaining increasing recognition. DIAGNOSIS OF CHRONIC PAIN: CARTESIAN DUALISM, PSYCHOBABBLE AND ARROGANT IGNORANCE Clinical features of chronic pain can be confusing and difficult to comprehend for the examining physician, leading to the characterization of the patient’s complaints as “non-organic”, “psychogenic”, “hysterical”, “somatizing”, and “hypochondriacal”, or as evidence of “illness/pain behavior”, “emotional overlay”, or even malingering. Especially puzzling is:

• Widespread regional or generalized pain
• Easily provoked pain, by even a mild physical workload
• Sense of peripheral muscular weakness and reduced endurance
• Diffuse and transient sensory abnormalities (dysesthesia)
• Regional or generalized hyperalgesia and/or allodynia, often with “jump-sign”
• Hyperalgesic muscle trigger points, with distally referred pain and/or dysesthesia that do not follow segmental or neuroanatomical patterns of distribution
• Delayed pain following physical examination, which may persist hours or days

  These features (we now recognize them as classical features of non-nociceptive pain) not only lead to the diagnosis of psychopathology (psychiatric or “functional” illness), but, more importantly, create a poisonous atmosphere in which the patient is blamed for “needing or creating” his pain, and is deprived of the necessary and effective treatment. Thus, it is imperative to keep in mind that medically unexplained pain – pain with non-anatomical characteristics, or incongruent with observable pathology, is NOT evidence of psychopathology. Frequently, the presence of psychological distress, and the elevated hysteria, hypochondriasis, and depression scales on the MMPI, which are the consequences of pain, are cited as the cause of pain (despite evidence that they normalize with improvement in pain). As well, both the success and failure of psychological treatment are attributed to psychological factors and “illness behavior”. Meanwhile, the challenge should remain for the modern-day Cartesian dualists to provide the empirical evidence and proof that psychopathology causes pain, and, in so doing, to specify the mechanisms by which it does! It is becoming increasingly apparent that the domain of the psychiatric “somatization” diagnosis is shrinking, as neuroscience keeps expanding our knowledge of NNP (non-nociceptive pain) mechanisms. We, as physicians, should heed the exhortations of the medical masters, past and present: “Pain must be regarded as a disease… and the physician’s first duty is action – heroic action – to fight disease”. (Benjamin Rush) “Few things a doctor does are more important than relieving pain… pain is soul destroying. No patient should have to endure intense pain unnecessarily. The quality of mercy is essential to the practice of medicine; here, of all places, it should not be strained”. (Marcia Angell)               TREATMENT OF CHRONIC PAIN DRUGS Historically, two herbs have provided humanity with pain relief: willow and poppy. Even today, 95% of the analgesics in use are derivatives of either ASA or opium. ASA and NSAIDS are usually the first line approach to the treatment of chronic pain, esp. pain of inflammatory variety. When combined with opioids, they may have a synergistic effect. ANTIDEPRESSANTS have been used with varying degrees of success. The most commonly used ones are amitriptyline and trazodone, since they also enhance SWS (slow-wave sleep, i.e., stage III and IV of sleep), a feature of particular advantage in treating fibromyalgia (cyproheptadine and zolpidem may be useful in this regard, too). Many other antidepressants have been used, including, more recently, the dopaminergic ones. Bupropion has been found useful in some cases of neuropathic pain.   ANTICONVULSANTS gabapentin and lamotrigine are generally used as the first line approach to the neuropathic pain. GABA agonists are also of considerable value; baclofen – a GABAB agonist – is particularly useful in treatment of spastic pains. AMPHETAMINES have been used in combination with opioids for treatment of severe, intractable pain. ALPHA-2 AGONISTS – clonidine – are sometimes extremely effective and highly synergistic when combined with opioids. SUBSTANCE P ANTAGONISTS have shown a potent analgesic effect in clinical trials, and at least one preparation should be available for general use soon. Interestingly, this same agent has been quite effective as an antidepressant, as well. CCK ANTAGONISTS – proglumide 200-250 mg p.o. – cancel CCK antagonism to opioids, augments opioid analgesia, and restores opioid effectiveness in neuropathic pain. NMDA-RECEPTOR ANTAGONISTS Recognition of NMDA-receptors as mediators of chronic pain has opened up a huge area of research. Drugs that block these receptors have a glorious potential in the treatment of chronic pain, esp. the neuropathic pain. When combined with opioids, they have a synergistic effect, and can restore opioid sensitivity in neuropathic pain. The currently available agents in N.America are ketamine (I.V. – 0.3mg/kg x 10 min.: substantial reduction in FM pain lasting 7 days), dextromethorphan (10-30 mg/kg B.I.D.), and amantadine, but two very promising agents in wide usage in Europe – flupirtine and memantine – should become available soon. Research on ziconotide – a snail venom derivative – looks extremely promising. OPIOIDS The most effective by far, and the most feared and underutilized drugs in the treatment of chronic pain are the opioid analgesics. Prejudice, paranoia and ignorance surrounding these drugs, are the main reasons behind the inadequate treatment of chronic pain and a colossal amount of unnecessary suffering that it causes. The main effects of opioids (both external and internal) are achieved through stimulation of the mu-opioid receptors. They amount to 70% of the spinal opioid receptors, while the share of delta and kappa receptors is about 25% and 5%, respectively. The vast majority of opioid receptors in the dorsal horn – about 70% of the total mu-receptors – are located on the pre-synaptic terminals, where

they potently inhibit the release of glutamate and substance P from the C-fiber afferents. Post-synaptically, they cause membrane hyperpolarization (preventing the NMDA-receptor activation and the wind-up phenomenon), while also stimulating the inhibitory GABA interneurons. The loss of pre-synaptic mu-receptors in injured or severed nerves, explains the reduced effectiveness of opioids in neuropathic pain. Opioid analgesia is usually initiated with the short half-life agents, given q 3-4 h: Morphine 15-30 mg Codeine 30-60 mg Oxycodone 10-15 mg Hydrocodone 10-15 mg Hydromorphone 2-4 mg Caution: CYP 2D6 inhibition reduces the effectiveness of codeine, oxycodone and hydrocodone (preventing formation of active metabolites). Once the effective drug is found (44% of patients required trials of 2 or more, while 20% required trials of 3 or more opioids), a sustained-release opioid is substituted, in the same daily dosage, given b.i.d. or even o.d. The 24-hour baseline dose, for sustained release opioids, is: Morphine 60 mg Codeine 200 mg Oxycodone 30 mg Hydrocodone 40 mg Hydromorphone 7.5 mg Methadone 20 mg Levorphanol 4 mg Fentanyl 25 microg transdermal patch, lasting 72 hours: equivalent to 45-135 mg/day of oral morphine; doesn’t pass through the liver, less constipation.   Oxycodone is the most utilized sustained-release opioid, due to fewer side-effects, easy titration and marked effectiveness in visceral pain (probably by added stimulation of kappa-receptors). Methadone and levorphanol are opioids with NMDA-antagonist effects, but are difficult to titrate, and exhibit delayed-onset side-effects, esp. sedation. Every patient on sustained-release agents should be provided with RESCUE MEDICATION – a fast-acting opioid to treat BREAK-THROUGH pain; this may be needed every 2-4 hours, in the dose that is 5-15% of the 24-hour baseline dose of the long-acting opioid.   SIDE EFFECTS The most feared side effects of opioid analgesia are tolerance and addiction – both totally unsubstantiated by clinical evidence. In the vast majority of chronic pain sufferers, tolerance and addiction DO NOT occur. What is encountered more frequently is PSEUDOADDICTION – appropriate demand for adequate pain control. Once the pain-relief dosage is established, it remains stable; if the disease progresses, or activity increases, titration to a higher stable dose is necessary. If rescue medication becomes unnecessary, or sedation appears, the dose can be slowly reduced. Inadequately treated pain is a much more important cause of opioid tolerance than use of opioids themselves!                 Other typical side effects are usually resolved within a few days to a week. Respiratory Depression: clinical evidence shows clearly that this does not occur when the drug is titrated against the patient’s pain. Nausea/Vomiting: occurs in 10-40% of pts, may require anti-emetics. Sedation: if intolerable, dose reduction by 25% may be required. Constipation: may be troublesome in over 50% of pts. Use bulk laxatives. Pruritus: may require non-sedating anti-histaminics during the first week. Myoclonus: very rare; benzos (clonazepam) useful. Side effects – result of the stimulation of non-opioid receptors – can be ingeniously managed by adding a miniscule dose (0.001% of the usual dose) of an opioid antagonist (e.g. naltrexone) to the opioid treatment regimen. Adding an NMDA or a CCK antagonist, or an alpha-2 adrenergic or GABA agonist, can frequently be effective in reducing the pain-relieving opioid dose.   SENSORY MODULATION Included here are various interventions that either block or modify the sensory input. These interventions can be quite effective, esp. when combined with adequate drug analgesia. Local anesthetic blocks, including sympathetic blocks, can sometimes provide remarkable relief, lasting days and weeks. Physical and electrical stimulation can be effective, and hypertonic saline injections can sometimes provide long-lasting relief. PSYCHOLOGICAL INTERVENTIONS Affective and cognitive dimensions of pain can be manipulated through psychological techniques, thus providing better gate control to the sensory input. CBT has been widely used and found helpful, and so has hypnosis, which can differentially influence the perception of the pain intensity, and the pain unpleasantness. Social support is of paramount importance, too. PLACEBO The placebo effect in pain is easier to comprehend if one views pain not as a stimulus, but as a sequence of appropriate motor responses to deal with the noxious stimulus:

1. Escape – from the noxious source, remove the source
2. Guard – assume protective posture, immobilize; to allow healing
3. Seek cure or remedy – go to healers, shamans, physicians

Appropriate action influences the affective-motivational and cognitive-evaluative dimensions of pain, thus potently activating the descending inhibitory controls. PET and fMRI studies of patients receiving an active drug or a placebo, furnish proof of the placebo effect being mediated by the internal opioid system – showing increased blood flow to the opioid receptors-rich areas in the anterior cingulate and lower brainstem. This effect can be totally blocked by naloxone (opioid antagonist), and attenuated by CCK; on the other hand, it can be augmented by CCK antagonists. REDEFINING PAIN   With this knowledge, let me elaborate now on a new perspective on pain, and provide a new definition of it. It is well known that damage to the anterior cingulate cortex (Brodmann’s area 24) abolishes the generation of pain, despite activation of nociceptive pathways (“I feel the pain, but it doesn’t hurt”). Thus, we may assert that pain is an emotion, a construct given by the intrinsic activity of the brain. As such, pain is not localizable; it may seem localized because of co-activation of pain – the emotional state and general tactile stimulation. “The unpleasantness of pain is an emotional state generated by the brain, not an event that somehow resides at a particular body location” (R.Llinas). This definition clearly implies that sensory pathways do not execute sensations; they only serve to inform the internal context (intrinsic activity of the brain) about the external world. In order to understand the states of pain, and devise more successful modes of pain treatment, it is imperative that we separate the carriers of sensory activity from the actual executors of sensation. Only through this approach will we be able to avoid perpetuating the noxious errors of Cartesian dualism, and reduce needless suffering of millions of people in chronic pain. In conclusion, I will reiterate “Few things a doctor does are more important than relieving pain”! D.Z.FULGOSI, MD, FRCP(C) CONCILIENCE HEALTH RESOURCES   Simple Sprain The Lumbar Spine extends from L1 (adjacent to the thoracic spine) down to L5 where it connects with the sacral bone . Simple Sprains usually occur when the low back is in a vulnerable position e.g. bending forwards and bent to one side whilst lifting shopping out of the boot of the car, or violent sneezing whilst bent forwards. The sprained part is usually in the superficial part of the spine (muscle, joint or ligament). The sprained tissue becomes inflamed, causing pain signals to be sent to the spinal cord. If the incoming pain signals are strong enough and go on for long enough, processing centres (dorsal horn) in the spinal cord become sensitised, sending out signals to the muscles in the vicinity of the sprain to contract to produce muscle spasm. This is initially a protective reflex which may prevent further injury to the sprained part. If the muscles in the area are contracting quite strongly, then the tension receptors in the local muscles and joints are activated. Strong signals from the tension receptors can be interpreted in the spinal cord as pain, adding to the pain signals from the inflamed tissue. These two kinds of signal combine together to keep the spinal cord dorsal horn in a sensitized state, and also keeping the spinal muscles in a contracted state through a feedback loop. The sequence of events can be therefore summarized in the diagram below:- Severe muscle spasm is a type of cramp, and like any other cramp in the body it hurts, causing restricted painful back movements. Over a variable period of time the initial back sprain heals, reducing the signals to the spinal cord, and also reducing the degree of spinal cord dorsal horn sensitization. Once this sensitization has declined, the outward signals to the muscles in the area of the sprain also lessen, allowing the pain and muscle spasm to resolve naturally. In about 10% of adults the back pain continues despite healing of the the initially sprained area. In this situation there is a perpetual loop as shown below, without there being any sprain or inflammatory process involved. This situation may leave individuals susceptible to further sprains due to the back muscles being in a contracted and shortened state, and also due to there being pre-existing dorsal horn sensitization.               Peripheral tissue or nerve injuries can lead to biochemicaland morphological changes within the corresponding area of the dorsal horn of the spinal cord. These changes can be longlastingand could account for the persistence of pain after the originalinsult has gone; they can also spread so that pain may be perceivedas coming from a much wider area. Increased sensitisation ofthe dorsal horn may account for hyperpathia and allodynia. Thesechanges could be responsible for the widespread sensitivityof the back and lower limbs to pressure commonly described bypatients with chronic back pain. Descending impulses from thebrain can also activate the sensitised dorsal horn so that apotential mechanism exists for integrating psychological distressand pain perception.12 Patients who are given centrally actinganalgesics before operation complain of less severe postoperativepain and wound hyperalgesia.13 The possibility of reducing thiscentral sensitisation has implications for treating back pain.       Some of the exercises require you to use a piece of Thera-Band for muscle strengthening. If required you can buy it from Physio Med. I would suggest red for the upper limb exercises, and green for the lower limb exercises. Depending on your physical capabilities, you may need to go higher or lower in the range. Flexion (Lying) This is a stretch to encourage Flexion in the lower lumbar spine. Basic Stretch

1. Clasp your hands in front of your knees, interlacing your fingers together. Make sure your neck is comfortable on a pillow.
2. Keep your knees together and gently use your arms to pull your knees towards your chest, stopping when you feel a tightness in your lower lumbar region. This is the barrier point.
3. You can now gently use your arms to move you knees backwards and forwards, in and out of this barrier point, for 5 minutes. Gradually you will feel that your knees are able to move closer to your chest as your back muscles begin to increase in length. A good tip is to breathe out as you pull your knees up, preventing your muscles from going into spasm.
4. The end point to this stretch is when you can get your knees right up to your chest, whilst raising your tail bone in the air.
5. If you can get your knees all the way up to your chest without any pulling sensation in the lower lumbar spine, then you have no significant muscle spasm in the lower lumbar area.
6. If it is too painful to clasp both your hands in front of both knees, try doing it with just one knee at a time, alternating between knees. alternatively try the MET stretch below first.
7. These stretches may not be suitable for those with severe hip arthritis as it may cause pain in the groin. Those with large stomachs and/or breasts may find it hard – but this should not be an excuse not to try!!

MET stretch

1. Clasp your hands in front of both of your knees, interlacing your fingers together. Make sure your neck is comfortable on a pillow.
2. Keep your knees together and gently use your arms to pull your knees towards your chest, stopping when you feel a tightness in your lower lumbar region. This is the barrier point.
3. At the barrier point, take a breath in and hold it (don’t let it go), push your knees against your hands for FIVE seconds, at about 25% maximum effort, not letting your knees move away from you. N.B. You are contracting your back muscles when you push against your knees like this.
4. Breath out quickly through your mouth, and relax all your muscles, but don’t let your knees move away from you. During the next THREE seconds, use your arms to move your knees 1-2 cm closer to your chest. Stop when you feel a pull in the back, this is your new barrier point. Hold your knees there using your arms, and don’t let your knees drift away from you.
5. Go to No.3 and start again. Go round this loop for 5 minutes, and you will find that gradually you will be able to get your knees all the way to your chest.
6. Those with severe back spasm will only be able to move their knees closer to their chest in small jumps, taking several days to achieve the goal. It is sometimes useful to try this technique with one leg at a time, and then progress to both legs. Those with lesser spasm will be able to achieve their goal more rapidly.

Flexion (Kneeling) This is a powerful stretch to encourage Flexion in the thoraco-lumbar spine.

1. Kneel on the bed with your knees together, and with your feet and bottom over the edge of the mattress. Be careful not to fall off.
2. Whilst breathing out, curl up in a ball, with hands out in front of you on the bed, and your face tucked down towards your knees – like “Praying to Mecca”. Hold this position for several minutes, using gentle breathing to aid relaxation.
3. You can make this a much more powerful stretch by clasping your hands in front of your shin bones, and using your arms to increase the amount forward flexion. Again hold this position for a few minutes, using gentle breathing to aid relaxation.

Rotation (Lying) These are stretches to encourage rotation in the lower thoracic spine and around the thoraco-lumbar junction. In the neutral position the lumbar spine will not rotate due to bony facet joint locking. Easy Stretch

1. Lie on your back with your feet and knees together, knees bent to 90 degrees and feet flat on the bed.
2. Whilst breathing out, let your knees drop to the left until they reach the bed, keeping your shoulders flat. Don’t hold your breath or close your voice box on the way down, as this will encourage the back muscles to tighten. Don’t rotate your upper trunk with your knees, as this will not produce any stretch at all.
3. Bring your knees back up again, and try the same thing to the right, again whilst breathing out.
4. When you are more confident, try swinging your knees from side to side rhythmically like a pendulum. If you can do this easily, then move on to the harder stretch.

Harder Stretch

1. Lie on your back, flexed at the hip with your thigh bones perpendicular, knees bent, and with your feet together not touching the bed. Have your arms away from your body at 90 degrees (like Jesus on the cross), holding on to the edge of the mattress, to help stabilise the upper trunk.
2. Whilst breathing out, let your knees drop to the left until they reach the bed, keeping your shoulders flat. Don’t hold your breath or close your voice box on the way down, as this will encourage the back muscles to tighten. Don’t rotate your upper trunk with your knees, as this will not produce any stretch at all.
3. Bring your knees back up again, and try the same thing to the right, again whilst breathing out.
4. When you are more confident, try swinging your knees from side to side rhythmically like a pendulum. If you can do this stretch easily then you don’t have significant thoraco-lumbar spasm.

Side Bending (Lying)

• This is a stretch to encourage side bending in the lumbar spine.
  1. Lie on your back with your legs flat, knees and feet together.
  2. Bend your elbows and fix your thumbs on top of the bony prominences on the front of your hip bones, and place your other fingers backwards around your hips/buttocks. You are trying to hold your pelvic bone in both hands.
  3. Push down with your left hand trying to make your left leg longer than the right, whilst hitching your right hip upwards. Don’t let your knees bend.
  4. Then push down with your right hand trying to make your right leg longer than the left, whilst hitching your left hip upwards. Again don’t let your knees bend.
  5. Try doing alternate movements smoothly and rhythmically, so that you end up doing a “buttock shuffle”.
  6. Women seem to be more coordinated at this than men for some reason !!

Quadratus Lumborum Basic Stretch This stretch helps encourage side bending in the lumbar spine.

1. Lie on your side (bad side uppermost) with your head supported on a pillow.
2. Place a rolled up towel in the gap between your ribs and hip bone.
3. Bend your lower leg up at the hip and knee, allowing your upper leg to drop down.
4. Raise your upper arm over your head encouraging side bending in the lumbar spine.
5. Try doing it on the other side as well.

Extension (Face Down) This is a stretch to encourage Extension of the lower thoracic and lumbar spine. It will also produce stretching of the abdominal muscles. People with spinal stenosis, foraminal stenosis, or an acute disc should not perform this stretch unless they have been instructed to do so by their doctor or physiotherapist.

1. Lie on your front with your feet together.
2. Prop yourself up on your elbows, arching your back and gently tipping your head backwards.
3. This stretch can be made more powerful by propping yourself up on your arms, either with the elbows bent, or the elbows straight. At all times your pelvis should be in contact with the surface of the mattress. Hold this stretch for a few minutes, using gentle breathing to aid relaxation.

Active Extensions These exercises are to strengthen the back and buttock muscles. Back Extensions

1. Lie on your front with your feet together.
2. Hold hands behind your bottom.
3. Move your hands downwards, whilst lifting your head and upper trunk off the bed and hold for FIVE seconds, dropping back down on to the mattress afterwards. You may need someone to hold on to your ankles for you.
4. Rest for a moment, before trying No.3 again.
5. Set an initial target of 10 repetitions, increasing the number by an extra 10 and so on, when you feel confident.

Leg Extensions

1. Lie on your front with your head resting on your forearms.
2. Lift your left leg backwards behind you, keeping the knee straight, and pointing your toes.
3. Hold for FIVE seconds, dropping back down on to the mattress afterwards.
4. Rest for a moment, before trying No.3 again.
5. Do the same sequence for the right leg.
6. Set an initial target of 10 repetitions for each leg, increasing the number by an extra 10 and so on, when you feel more confident.

General Co-ordination

1. Get onto your hands and knees on the mattress, keeping your arms, thighs and back fairly straight.
2. Hold your left arm out in front of you horizontally in line with your body, as well as extending your right leg behind you horizontally in line with your body, ending up balancing on the mattress supported on your right hand and left knee (just like a lizard in the desert standing on hot sand !!)
3. Hold this for FIVE seconds, releasing the position so that you end up on your hands and knees again.
4. Hold your right arm out in front of you horizontally in line with your body, as well as extending your left leg behind you horizontally in line with your body, ending up balancing on the mattress supported on your left hand and right knee (mirror image of No.2 above).
5. Set an initial target of 10 repetitions for each version, increasing the number by an extra 10 and so on, when you feel confident.

Abdominal Muscles These exercises are to strengthen the abdominal muscles. About 50% of the support for the spine comes from these muscles, and they also have a very important role during lifting. Therefore strong abdominal muscles are crucial to prevent the spine being vulnerable to injury. For abdominal muscles stretches look at Extension (Face Down). Upper Abdominal Exercises

• Part 1
  • Lie on your back with your feet and knees together, knees bent to 90 degrees and feet flat on the bed.
  • With your arms out stretched place your finger tips on your knees.
  • Hold this position for FIVE seconds, dropping back down on to the bed afterwards.
  • Pause for a moment, before trying it again.
• Part 2
  • Do the same exercise placing your right finger tips on your left knee.
  • Hold this position for FIVE seconds, dropping back down on to the bed afterwards.
  • Pause for a moment, before trying it again.
  • Do the same exercise placing your left finger tips on your right knee.
  • Set an initial target of 10 repetitions for each of the three exercises, increasing the number by an extra 10 and so on, when you feel confident.

Lower Abdominal Exercises

• Easy
  1. Lie on your back with your legs flat and feet together.
  2. Slowly bring your knees up together, so that your hips and knees are each bent at 90 degrees, with your thigh bones perpendicular to the mattress.
  3. Whilst breathing out, slowly lower your legs down to the mattress over about FIVE seconds, keeping your knees together, ending up with your legs straight, being careful not to arch your back.
  4. Set an initial target of 10 repetitions, increasing the number by an extra 10 and so on, when you feel confident.
• Hard (don’t do this one if you have moderate / severe back pain)
  1. Lie on your back with your legs flat and feet together.
  2. Slowly raise both legs up together with your knees straight, until they are pointing up at the ceiling, bent 90 degrees at the hip.
  3. Whilst breathing out, slowly lower your legs down to the mattress over about FIVE seconds, keeping your knees together, ending up with your legs straight, being careful not to arch your back.
  4. Set an initial target of 10 repetitions, increasing the number by an extra 10 and so on, when you feel confident.

CAT Exercise Designed to train Transversus Abdominis the deepest abdominal muscle, important for spinal stability and strength.

• Part 1
  • Get onto your hands and knees on the mattress, keeping your back fairly straight. Relax your back and abdominal muscles, allowing them both to sag downwards as much as possible, and hold for a few seconds. Don’t let your arms bend.
• Part 2
  • Next arch your back upwards “like an angry cat”, whilst trying to suck your abdominal muscles upwards. Tip – try closing your voice box and breathing in at the same time. Imagine that you are trying to make your tummy button touch your spine. Hold for a few seconds then relax.
  • Repeat Parts 1 and 2 in sequence, setting an initial target of 10 repetitions, increasing the number by an extra 10 and so on, when you feel confident.

Pelvic Tilts

1. Lie on your back with both feet on the floor, knees and hips flexed, hands palm down beside you.
2. Push you bottom into the floor arching your lower back as far as possible, and hold for a few seconds.
3. Do the reverse movement by lifting your bottom off the floor whilst thrusting you pelvis forwards, and hold for a few seconds. Keep as much of your lower back in contact with the floor as possible, this concentrates the exercise around the lumbo-pelvic junction.
4. Go to No.2 and repeat.
5. Set an initial target of 10 repetitions, increasing the number by an extra 10 and so on, when you feel confident.
6. When you are confident try developing a continuous continuous movement from no.2 to no.3 without pausing in between.

  Peripheral sensitization causing decreased activation threshold of receptors and shortened response latency this results in hyperalgesia Fibers in the CNS are induced to carry nociceptive input without normal dorsal root inhibition constant bombardment of CNS overwhelms filtering Pain can actually cause muscle spasm and sympathetic outflow   CNS sensitization is called wind-up     PAIN: OF COURSE IT’S ALL IN YOUR HEAD NEUROBIOLOGY OF PAIN DEFINITION   IASP: “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. Even the authors were aware of this definition’s inadequacy, and hastened to add: “Pain is always subjective… This definition avoids tying pain to the stimulus”. Despite the disclaimer, this definition DOES tie the sensation to the stimulus, perpetuating the centuries old fallacy. It does not, and cannot, explain many of the perplexing aspects of pain experience, and it does not consider the crucial influence of the brain on the sensation and the perception of pain. 1. The brain can generate pain, create a perceptual experience, independent of the peripheral input, i.e., regardless of the presence or the extent of tissue damage or pathology. 2. The brain is continually modified by experience and sensory input. THE PUZZLE OF PAIN Without the contributions of modern neuroscience, it is impossible to unravel the multitude of the pain puzzles: 1. Well known instances of NO PAIN with major injuries 2. Excruciating PAIN in missing structures (phantom pains), or denervated structures (below spinal cord section in paraplegics) 3. PAIN persisting, after complete healing of injury 4. PAIN provoked by touch, or no stimulus at all 5. PAIN that is delayed, or non-anatomically spread NOCICEPTION AND PAIN PATHWAYS Stimuli from the periphery (mechanical, chemical, thermal) are transmitted to the spinal cord through the sensory afferent nerves. Damaged tissue is a source of many amines and peptides that stimulate sensory nerve endings: bradykinin, adrenaline, 5HT, PGE2, IL-1, IL-6, TNF-alpha, etc. These afferents synapse on the dorsal horn second order neurons in the spinal column (projection neurons), which form pathways extending to the brain – primarily thalamus and somato-sensory cortex. Acute, physiological pain is mediated in the spinal synapses mainly by the GLUTAMATE-activated AMPA type of glutamate receptors. In addition to glutamate, excitatory transmitters include AcCh, substance P, and CGRP, while GABA, enkephalin, 5HT and NA provide the inhibitory neurotransmission. NEUROBIOLOGY OF CHRONIC PAIN Chronic pain is not just a prolonged acute pain; it is a distinct entity, with many functional and structural alterations of the peripheral and central nervous system. ERIPHERAL SENSITIZATION – PRIMARY HYPERALGESIA Peripheral nociceptive hyperexcitability is induced through increased receptor (autosensitization) or cell membrane (heterosensitization) reactivity to stimuli, usually sustained presence of inflammatory factors. CENTRAL SENSITIZATION – SECONDARY HYPERALGESIA Central hyperexcitability is the key process in the generation of chronic pain. It is mediated by NMDA-type of post-synaptic glutamate receptors, and it results in transcriptional changes and manufacturing of the c-fos protein (the marker of central sensitization) in the second order dorsal horn projection neurons. Repetitious and intense activation of the high-threshold C-fibers and AMPA post-synaptic receptors results in activation of the NMDA post-synaptic receptors (through dislodging the Mg ions and opening the N and Ca channels to Ca influx) and the NMDA mediated WIND-UP phenomenon (augmented response of the dorsal horn neurons to the same intensity stimuli). Activation of the NMDA-receptors represents the first step in central sensitization, i.e., the transition from acute to chronic pain. Knowing this makes it easy to realize that adequate treatment of physiological, nociceptive pain is the most important goal of acute pain management – prevention of central sensitization! PAIN Page 1 of 7 http://www.medicalmasterclass.com/pain. Fulgosi.htm 3/7/2006 Other changes involved in central sensitization include substance P – NO (nitric oxide) cascade (with expansion of the receptive fields), increased release of NPY, VIP, galanin, and somatostatin from the pre-synaptic C-fiber terminals, hyper-sensitization of the WDR (wide dynamic range) neurons to non-nociceptive stimuli, expression of substance P by A-fiber pre-synaptic terminals, and sprouting of A-fiber terminals into the superficial layers of the dorsal horn (thus synapsing onto the nociceptive second order neurons). Reorganization or remodelling of the synapses at the dorsal horn level, as well as at the brainstem, thalamus, and somatosensory cortex levels, is a well-documented phenomenon, referred to as neuronal plasticity, responsible for a variety of chronic pain syndromes. Central sensitization and neuroplastic remodeling are responsible for all the main features of chronic pain: hypersensitivity to nociceptive stimuli (hyperalgesia), perception of pain upon non-nociceptive stimulation (NNP and allodynia), expansion of the pain-receptive fields and trigger-zones, and delayed pain. Changes in central sensitization can be viewed as: 1. FUNCTIONAL (NEUROCHEMICAL) HYPEREXCITABILITY: Activation of the NMDA- receptors, wind-up, sensitization of WDR neurons, expression of substance P by A-fibers 2. STRUCTURAL (NEUROANATOMICAL) HYPEREXCITABILITY: Dying-off of C-fiber terminals, sprouting of A-fiber terminals, extensive reorganization of the somatosensory cortical maps, remodeling in the brainstem, cerebellum, basal ganglia, and motor cortical areas. DYSFUNCTIONAL DESCENDING INHIBITION – FAILURE OF INTERNAL ANTINOCICEPTION As illustrated in PAIN PATHWAYS, nociception activates not only the afferent pathways, but also a variety of segmental and descending, inhibitory or antinociceptive pathways (SLIDE 5). Increased brainstem CCK, and deficiencies in the descending enkephalin, 5HT, and NA pathways, can all contribute to dysfunctional anti-nociception. Processing of pain at the brain level has profound implications for both, the perception of pain, and for the management of pain. Ascending pain pathways are relayed through the thalamus to the somatosensory cortex, which is responsible for the initial localization and the intensity of the stimulus (SENSORY-DISCRIMINATIVE function), as well as to the limbic brain structures, esp. the anterior cingulated cortex, which is responsible for the unpleasant, aversive aspect of the experience (AFFECTIVE-MOTIVATIONAL function). Both of these areas communicate extensively and reciprocally with the prefrontal cortex, which brings the situational and memory context to the experience (COGNITIVE-EVALUATIVE function). These three aspects of pain experience (R. Melzack’s gate and neuromatrix theory of pain) make a variety of pain treatment modalities potentially helpful, and at the same time provide the neurophysiological and neurostructural explanation of these modalities’ efficacy (dismissing, in the process, all kinds of hogwash that has been written about “psychogenesis” of pain). CHRONIC PAIN SYNDROMES Chronic pain is generally categorized, according to etiological factors, as stemming from tissue damage – inflammatory pain, or from nerve damage – neuropathic pain. The former is evident in various injuries (low back pain), infections, inflammatory diseases (RA, IBD, SLE) and immune/neuroendocrine dysfunctions (possibly FM/CFS, MPS). The latter is encountered in diabetes, certain infections (shingles), cancer, traumatic nerve injury, and following amputations (limb, breast). Opioids are exceedingly effective in managing inflammatory pain, whereas they are less effective in managing neuropathic pain, due to the loss of pre-synaptic opioid receptors, and the extensive re-wiring of the dorsal horn synaptic circuits. Low back pain In up to 85% of sufferers, there is no detectable damage (“no objectively demonstrable organic pathology”); in only about 15% can one of the five recognizable causes (herniated disc, arthritis, infection, tumor or fracture) be demonstrated. In addition, it is estimated that about 10% of low back pains develop a neuropathic dimension, making the picture even more puzzling. The vast majority of chronic low back pain sufferers continue to be under-treated or maltreated, labeled as “somatizers” or malingerers, despite ample evidence for central sensitization and somatosensory mapping reorganization in such patients. Fibromyalgia and Myofascial Pain Syndrome There is ample evidence in these disorders, as well, of altered central processing of the incoming nociceptive and non-nociceptive stimuli, at both the spinal and the brain level. Incoming stimuli from muscle C-fiber afferents are much more potent inducers of central sensitization than skin afferents, explaining lower pain threshold PAIN Page 2 of 7 http://www.medicalmasterclass.com/pain. Fulgosi.htm 3/7/2006 (hyperalgesia) and pain on movement (proprioceptive allodynia) in these patients. In addition, a dysregulated neuroendocrine stress response (decreased cortisol, growth hormone and IGF-1 secretion) may compound the picture in about a third of patients. Phantom limb pain Phantom pains affect over 70% of amputees, and persist for 2-7 years in about 60% of them; fewer than 15% obtain total pain relief. Extensive somatosensory cortex reorganization, with expansion of the trigger zones, has been demonstrated in numerous brain imaging studies. Peripheral ectopic discharges (from the stump neuroma), deafferentation hyperexcitability, and unmasking of the underlying silent connections, may all be contributory. In addition to phantom limb pain, phantom pains following mastectomy, and phantom body pains below the spinal cord section in paraplegics, are gaining increasing recognition. DIAGNOSIS OF CHRONIC PAIN: CARTESIAN DUALISM, PSYCHOBABBLE AND ARROGANT IGNORANCE Clinical features of chronic pain can be confusing and difficult to comprehend for the examining physician, leading to the characterization of the patient’s complaints as “non-organic”, “psychogenic”, “hysterical”, “somatizing”, and “hypochondriacal”, or as evidence of “illness/pain behavior”, “emotional overlay”, or even malingering. Especially puzzling is: