Chronic Pain Management

Chronic Pain Management

Chronic Pain Management CME Conference Swedish Hospital September 28, 2010 Jonathan Clapp, MD Colorado Comprehensive Spine Institute 3277 S. Lincoln St. Englewood, CO 80113 Disclosures Objectives Describe what chronic pain is and how it is thought to occur. Illustrate the many issues involved in a typical patient. Discuss the bio-psycho-social model of diagnosis and treatment. Outline medications and alternatives used to manage chronic pain.

What is Pain? Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. -IASP Pain is a subjective and entirely individual personal experience influenced by learning, context, and multiple psychosocial variables. Chronic Pain Definitions Pain lasting longer than anticipated within the context of

the usual course of an acute disease or injury. Pain lasting 3-6 months following the inciting event, and in many cases may not be associated with any obvious ongoing noxious event or pathologic process. Pain that no longer serves as a physiologic protective mechanism. DSM IV Pain Disorder Criteria: Pain in 1 or more anatomic sites. Pain causes significant distress or impairment. Psychological factors are judged to play an important role. Symptom(s) are not intentionally produced. Pain is not better accounted for by another condition. Chronic Pain

Often occurs with poor sleep and decreased function. Frequently results in dysfunctional behaviors, suffering and disability. Is different from acute pain in that it can involve biologic, psychologic and socioeconomic issues. a multidisciplinary team approach the best means of comprehensive treatment. Chronic Pain More than 75% of chronic pain patients display harmful behavioral

characteristics. Problems with job or housework, leisure activities, sexual function and vocational endeavors. Chronic Pain Epidemiology Approximately from 30-40% in gen. pop. >70% in patients with a primary disability SCI, MS, amputations & cerebral palsy >36

million with arthritis, 70 million with chronic back pain, 20 million with migraines and additional millions with gout, myofascial pain syndromes, cancer and complex regional pain syndromes By 2030 arthritis and related disability is expected to almost double, affecting 71 million Americans. Chronic Pain Costs $70-120 billion annually for healthcare and lost productivity. Annually responsible for 90 million physician visits, 14% of all prescriptions, and 50 million lost workdays. Types of Chronic Pain

Somatic: Osteoarthritis, back pain, headaches, rheumatoid arthritis, osteomyelitis, post-surgical Visceral: pelvic pain, interstitial cystitis, pancreatitis, endometriosis Neuropathic: Complex regional pain syndrome (CRPS), post-herpetic neuralgia, diabetic neuropathy, phantom limb pain, post stroke, chronic radiculopathy, fibromyalgia, trigeminal neuralgia. J.P. Schneider, MD. A Practical Introduction to the use of Opioids for Chronic Pain. PowerPoint. AAPM Conference, October 2009. Pain Receptors & Pathways Transduction: Receptor Activation Energy that is damaging or potentially damaging (thermal, mechanical or chemical energy) is converted into action potentials in primary nerve

afferents. Primary receptors for pain lie at the terminal branches of C and A-delta fibers that both respond to a painful stimulus at a cellular level. Pain Receptors & Pathways Transmission Impulses are transferred from primary afferents to the dorsal horn, brainstem, thalamus, and cortical structures. C-fibers: 70% of skin nociceptors, slow, thin, unmyelinated A-delta fibers: 10% of skin nociceptors, rapid, medium, thinly myelinated.

Transmit the slow, burning quality of pain Transmit the fast, prickly quality of pain Contribute to hyperpathia with sensitization. A-beta fibers: 20% of skin nociceptors, fast, large, myelinated. Carry non-painful impulses (touch, vibration, pressure), except with peripheral and central sensitization, which can result in allodynia. Pain Receptors & Pathways Modulation

Primary afferents converge at the dorsal horn, with A-delta and C fibers synapsing on superficial laminae (I & II) and deep laminae (V & VI). Superficial laminae are involved primarily in nociceptive inputs Deep laminae respond to wide dynamic range neurons (WDR) of wide stimulus intensities. Non painful afferent impulses in A-beta fibers, for example, release glutamate which acts on NMDA receptors to block it via magnesium release and on AMPA receptors to activate it via normal sodium channel opening. However, prolonged post-synaptic depolarization causes voltagedependent Mg removal, allowing additional Na and Ca to enter the cell, resulting in amplified/painful responses with further impulses. Pain Receptors & Pathways Ascending & Descending Modulation

Endogenous Inhibition The periaqueductal gray in the pons is important in modulating nociceptive inhibition and behavioral responses to potentially threatening stimuli via endogenous opioids. Serotonin, norepinephrine, acetycholine and GABA also, in general, act to inhibit pain signals. Glutamate and substance P are excitatory neurotransmitters and ramp up the pain response. Ascending & Descending Modulation Descending Pathways Periaqueductal Gray Matter

Ascending Pathways Nucleus Raphe Magnus C fibers A-delta fibers Key: H = hypothalamus IL = intralaminar thalamic nuclei L = limbic system PT = post. thalamic nuclei VPL = ventral posterior thalamic nuclei Lateral System Medial System The Role of Endogenous Opioids

To reduce the level of perceived pain, endogenous opioids (enkephalins, dynorphin) are released by interneurons in the dorsal horn in response to severe/persistent pain. The opioids bind to G proteins associated with -type opioid receptors, with the following results: Inhibition of pre-synaptic release of glutamate Increased potassium conductance across the post-synaptic membrane These events prevent the transmission of pain to the higher centers To combat pain, exogenous opioids (e.g. morphine) mimic the effects of endogenous opioids at the opioid receptors.

fMRI studies in fibromyalgia patients suggest that similar levels of subjective pain result in similar central nervous system (CNS) activation in both fibromyalgia patients and controls. For a similar stimulus, however, fibromyalgia patients have a greater subjective sensation of pain. This increased sensitivity is accompanied with a decreased activity in brain regions implicated in the descending pain inhibitory pathways. Mainguy Y. Functional magnetic resonance imagery (fMRI) in fibromyalgia and the response to milnacipran. Hum Psychopharmacol. 2009 Jun;24 Suppl 1:S19-23. Psychologic Factors in Chronic Pain Affective & Cognitive factors have a large impact on the perception of pain. Studies show depressed patients have higher levels of pain, decreased cognitive functioning, & greater disability.

Anxiety is a strong predictor of pain severity, disability and pain behavior. Patients with pain-related fear had increased disability at 6 months. Operant Behavior Operant, or learned, pain behavior can have a significant impact on the lives of chronic pain patients. Patients learn to avoid potentially painful activities via punishment (pain) and achieve rewards (reduction of pain). Reinforced by a physician lack of understanding of this chronic disease process. untreatable

These principles can extend into other, more complicated, aspects of their lives based on: Rewards: attention/affection, financial (disability), etc. Punishment: returning to work, anxiety/fear with activity (kinesophobia), increased pain with independence, lack of understanding, etc. Sleep & Chronic Pain 8-8 hrs is considered restorative.

About 20% is spent in Stages 3 & 4 (delta-wave, slow-wave, or deep sleep) which is considered the most important/ restorative part of the sleep cycle. Is affected by many medications (opioids, benzos, etc.) 50-90% prevalence of disturbed sleep in chronic pain patients. Possible role of decreased serotonin, besides the obvious pain that can wake patients. Assessment HPI

Dx? Onset In temporal order, what was tried (surgery, injections, meds, PT, bracing, acupuncture, meditation, etc)? Did each intervention help or not? A 30% reduction in pain is considered clinically significant. If they were in therapy, what did they specifically do? How often and how long? Pain Hx For

each complaint: Where, ?/10, constant or intermittent, quality (burning, sharp, ache, pins & needles, etc.), exacerbating/relieving factors, radiating?, am/pm differences? Assessment Functional Hx Sleep Hx Is there anything they cannot, or have trouble doing? Assistance required? On disability or working? When do they go to bed? How long to fall asleep? Wake up how many

times per night? How long to fall back asleep? What time do they wake for the day? Do they feel rested? Psych Hx A semistructured interview by an experienced psychologist/psychiatrist is the most comprehensive means of evaluating the psychologic state of the patient. Expectations of treatment? Hx of abuse? Relationships? Pain behaviors? Stressed? Depressed? Under any treatment? DSM IV Criteria (+4/8 = major depression) Sleep disturbances, decreased interests, guilt, energy, cognitive slowing, appetite changes, psychomotor slowing, decreased sex drive, suicidality. Assessment ROS

PMH PSxHx FH SH Make sure that nobody else is prescribing pain medications. Allergies Diagnostic tests

Smoking, EtOH, illicits? Living situation? Employment status (employed? what kind of work? Restrictions? Full or part-time? Meds check SEs of current meds or sxs that may be increased by additional interventions. Keep in close dialogue with other professionals involved in pxs care. Vitals Detailed physical exam Affect, alertness, speech, pupils, provocative movts, specialized tests, tenderness, asymmetry, swelling, redness, heat, cold, soft tissue abnormalities,

hyperpathia or allodynia, radicular or nerve distribution. Treatment Studies show multidisciplinary approaches are unequivocally the best model in pxs with short& long-term disability. Team should optimally include: Physician, PT, OT, Pain Psychologist/Psychiatrist, Social Worker, Recreational Therapist, Biofeedback Specialist (may be covered by psych.), Nursing Educator, Vocational Counselor The team should work together to provide a unified diagnosis and comprehensive treatment program, in which the patient is an active participant. Team Goals of Treatment

Maximize & maintain physical activity and function Reduce the misuse or abuse of dependency-producing meds, invasive procedures, and passive modalities, fostered by a change toward active patient self management. Return to previous levels of activity at home, in the workplace and in leisure pursuits. Reduce subjective reported pain intensity and maladaptive pain behaviors. Assist patients in obtaining resolution and/or closure of contentious work-related or litigation aspects of the pain condition. Treatment/Modalities

Heat & Cold Via unknown mechanisms, cutaneous heat & cold both serve to reduce muscle spasms by decreasing sensitivity of the muscle spindles firing rate and returning it to its normal length. Cold is better for acute/inflammatory injuries, but can be used long-term based on pxs preference for muscle tightness. Heat/Ultrasound is best tolerated in subacute/chronic conditions, but is better for loosening collagen and stiff joints than cryotherapy. Treatment/Modalities Transcutaneous Electrical Nerve Stimulation Therapy (TENS)

Theoretically acts via the gate control theory, electrical stimulation preferentially activates large diameter fibers, inhibiting smaller pain fibers. May involve release of endogenous opioids, as well. No better than placebo for chronic LBP, but does help with CRPS, phantom limb pain, peripheral nerve injury and post-op incisional pain. Contraindicated in pxs with pacemakers. Treatment/Modalities: Exercise Muscles may shorten as a protective reaction to injury/pain.

Prolonged shortening can be a cause of pain and result in altered biomechanics. Graded stretching and strengthening, massage and manual therapy can help restore normal body mechanics. Exercise itself is an important pain reducer, as well. 20 minutes of aerobic exercise per day has been shown to decrease depression, increase self efficacy and increase the release of endogenous opioids. Movement-Based Therapies

Aquatic Rehabilitation is ideal for pxs with fear and anxiety related to movement. Pilates focuses on core strengthening, power, concentration, breathing and kinesthetic awareness. Weight bearing is decreased 40% in chest deep water & allows for progressive loading. Resistive force of water = force produced by px Reports of reduced pain, anxiety, depression, fatigue and increased quality of life for up to 24 months. Little literature, but reports of improved strength, flexibility & posture.

Yoga has been reported to reduce pain possibly due to control of stress & depression as well as working on relaxation, stretching & strengthening of targeted muscles. Behavioral Treatment Modalities Cognitive behavior modification teaches self-coping statements and problem-solving cognitions in attempts to alter their perception of their chronic disease. Strategies of imaginative inattention, imaginative transformation of pain, focused attention & somatization in a dissociation manner are used. The operant approach reinforces good behavior and ignores adverse pain behavior. Relaxation Methods involve voluntarily sequentially contracting and relaxing muscle groups.

Exercises should be done at a level to avoid punishment for activity and reinforce the positive and reward them for achieving goals. Allows insight into sensing muscle tension, facilitating relaxation. Strong support for use in treating anxiety, depression, HA, insomnia & chronic pain. Biofeedback teaches muscle relaxation and help teach the px selfregulation of pain. Include imagery, hypnosis, meditation, diaphragmatic breathing. Positive effects in chronic LBP, FM, HA, and temporomandibular disorders. Alternative Therapies/Integrative Approach When evaluating treatments for our patients, we shouldnt only look at the

number to treat, but we should also look at the costs and risks. -Dr. Andrew Weil If there is something out there that may help our patients, when conventional medicine has failed; if it has little risk and is not overly expensive, should we be so quick to dismiss it? TENS unit is a good example Treatment/Modalities Acupuncture 2,500 year old Chinese modality aimed at restoring the balance between the yin (blood) and the yang (spirit)

which flow in 14 channels or meridians containing 361 acupuncture sites. Two theories of action: May stimulate large afferent fibers via the gate control theory May induce endogenous opiate-like substances to effect pain control. Insertion of a needle, regardless of substance injected, can reduce pain. Called the needle effect. A NIH panel in 1997 concluded there is clear evidence that acupuncture is effective for pregnancy, postoperative and chemotherapy associated N/V, and post-op dental pain. Also concluded that there are other pain-related conditions for which acupuncture may be effective, despite less

convincing scientific data. Addiction, stroke rehabilitation, headache, menstrual cramps, tennis elbow, fibromyalgia (general muscle pain), low back pain, carpal tunnel syndrome, and asthma. Movement-Based Therapies Feldenkrais involves slow, fluid reaching, gentle stretching & postural changes for improved kinesthetic awareness & psychologic well-being. Uses verbal cues and touch to facilitate movement. Reported to improve QOL and self-efficacy in pain pxs. Also decreases anxiety & improves mood. Can be done in gravity-eliminated positions, like laying down.

Tai chi supreme ultimate boxing integrates sharp mental focus with slow, rhythmic, dancelike movt sequences & postures that unite mind & body by facilitating the flow of qi throughout the body. Reports of helping with pain, strength & flexibility. Acupuncture

Life Energy Flow Tai Yi Reflexology Craniosacral Therapy Meditation Stress Management Healing Rhythms Movement Therapy Therapeutic Massage Laughter Yoga Nutrition Counseling Yoga and Yoga Therapy Nutrition Vit D, B12, B6, and essential fatty acid deficiencies can cause pain. Excess Omega-6 fatty acids without appropriate balance with Omega-3 fatty acids results in inflammatory mediators that are more reactive. Herbal Supplements

Inflammation: Via unknown mechanisms, S-adenosylmethionine (SAMe) 600mg BID shown to be as effective as celebrex in knee OA after 2 months of treatment and as effective as TCAs in treatment of depression. Omega-3 supplementation 2.7g/day of EPA & DHA improves pain in RA, OA & IBS after 3 months. Rec BID dosing. Ginger up to 4grams/day in divided doses. Sleep dysfunction: Melatonin, passionflower, casein, 5-HTP, Valerian root Nerve pain: Alpha-lipoic acid up to 600mg/day in divided doses.

(Najm WI, et al. BMC Musculoskelet Disord. 2004 Feb 26; 5:6) (Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence 1,2,3,4American Journal of Clinical Nutrition, Vol. 76, No. 5, 1158S-1161S, November 2002 2002). Goldberg RJ, Katz J. Pain 129 (2007) 210-223 Acetaminophen NSAIDs Low Potency Opioids High Potency Opiods WHO Pain Pyramid Gruft, 2005 Acetaminophen Tramadol & Adjuvant Drugs Low Potency Opioids High Potency Opiods

Chronic Pain Pyramid NSAIDs Are ideal for acute conditions (2-3 weeks) to reduce inflammation (except Tylenol) and pain by selectively or non-selectively blocking COX-1&2 pain producing cascades and prostaglandin synthesis. COX-2 is suggested to be more associated with pain via its involvement in peripheral and central sensitization and in mechanisms underlying neuroplastic changes in chronic pain. Also inhibit tissue reaction to bradykinin, suppress release of histamine and decrease vascular permeability. All NSAIDs have a ceiling effect.

NSAIDs Should be avoided in chronic pain due to GI bleeding (most common 5-10%), renal toxicity, platelet dysfunction & cardiac complications. In 2004, based on review of literature re: NSAIDs, the FDA concluded that adverse CV effects may be a class effect for all NSAIDs (except aspirin). Other NSAIDs can actually block the cardioprotective effects of ASA. Ongoing monitoring of BP, hematologic status, and cardiac & kidney function is recommended for pxs on chronic selective & non-selective NSAIDs.

aspirin The original & standard NSAID. Only one with cardioprotective qualities. Irreversibly blocks thromboxane A2 in platelets, blocking platelet aggregation. Higher rate of gastric irritation (up to 40%).

Single dose can last 8-10 days. Misoprostol can help preserve gastric lining Do not give to children with flu like sxs or chicken pox to prevent Reyes Syndrome. Toxicity presents as HA, confusion, tinnitus, N/V & hyperventilation if severe. Analgesic Dose: 325-650mg/day (max 4g) Onset: 15-30 min life: 3-6h May take 2 weeks for therapeutic response to arthritis. acetaminophen Well tolerated NSAID in children and pregnancy. Usually 1st line.

Dose: 325-1000mg Q4-6h (4g daily max). Onset: 15-30min life: 3-6h Analgesic & antipyretic 4g/day may produce fatal hepatic necrosis. Unclear mechanism Less with EtOH Look for N/V and abdominal pain Give activated charcoal

Can also produce renal tubular necrosis. ibuprofen Good, inexpensive choice for acute pain conditions due to its ability to decrease inflammation & pain. Dose: TID or QID dosing >1600mg/day needed for anti-inflammatory action. Dont exceed 2400mg/day. Onset: 30 min

life: 2-4h Also inhibits platelet aggregation & antipyretic However, was shown to block the cardioprotective effects of ASA in a study of over 7,000 patients. Should, therefore be avoided, along with other NSAIDs (except celecoxib) if px requires ASA. celecoxib Only COX-2 inhibitor on the market. Less common GI effects through sparing COX-1. Dose: 100-200mg daily (200mg max dose)

Onset: <60min life: 9-10h Higher risk of CV events with COX-2s than other NSAIDs. Black-Box Warning from FDA. Pfizer sponsored study showed no increased risk compared to other NSAIDs at doses of 200mg/day or less. 400mg/day showed a 2.3-fold increase in risk 800mg/day showed a 3.4-fold increase Opioids Work by binding 3 opioid receptors (mu, delta & kappa). Presynaptically:

inhibit calcium influx, decreasing release of excitatory neurotransmitters (serotonin, norepi-, substance P & glutamate). Postsynaptically: hyperpolarize by increasing K influx. In Brainstem: inhibit GABAergic transmission, causing enhanced descending inhibition. Opioids SEs include: sedation, decreased cognition, poor concentration, lethargy, decreased mental & physical performance constipation, N/V hypothalamic-pituitary-adrenal/gonadal alterations. Decreased testosterone, progesterone & estradiol causing decreased energy & libido, requiring supplementation.

Decreased cortisol response to stress tolerance, physical & psychological dependence possibly fatal impaired respiration or bradycardia. Some evidence that COAT may have a pronociceptive effect over time. CBME Guidelines for Prescribing Opioids The CBME strongly urges physicians to view effective pain management as a high priority in all patients. Tx may involve several drug and non-drug tx modalities, often in combination. Pain should be assessed and treated promptly, effectively, and for as long as

pain persists. Drugs, particularly the opioid analgesics, are considered the cornerstone of treatment for pain associated with trauma, surgery, medical procedures, and cancer. Colorado Board of Medical Examiners: Guidelines for Prescribing Controlled Substances for Chronic Non-Malignant Pain CBME Guidelines for Prescribing Opioids Addiction vs. Physical Dependence Physical dependence and tolerance are normal physiologic

consequences of extended opioid therapy and are not the same as addiction. Patients with chronic pain should not be considered addicts merely because they are being treated with opiates. Tolerance resulting in decreased pain control is much rarer than decreased side effects, especially altered cognition. Addiction is a behavioral syndrome characterized by psychological dependence and aberrant drug-related behaviors. compulsively uses drugs for non-medical purposes despite harmful effects Colorado Board of Medical Examiners: Guidelines for Prescribing Controlled Substances for Chronic Non-Malignant Pain COAT & Chronic Pain Mixed opinions regarding chronic opioid analgesic therapy (COAT). Pain reduction is well documented, but debate occurs over whether

there is an increase in function and whether risks of dependency, sedation, and other SEs are worth the benefits. Many different criteria used in these studies. One study showed decreased function, increased pain & healthcare utilization with associated benzodiazepine use, but not opioids alone. Haythornthwaite et al. showed reduced pain, anxiety & hostility without decreased cognition in 19 pxs. Chabal et al. Conflicts arise when incomplete models are used to address a complex problem Actually showed increase in psychomotor speed & sustained attention compared to untreated pain patients.

A review of 48 studies (Fishbain et al.) showed moderate evidence for no impairment of psychomotor abilities in opioid dependent pxs & strong evidence for no increase in MVAs or violations vs. controls (also demonstrated in driving simulators). Further supported by study reporting cognitive deficits in opioid nave/healthy pxs and not in COAT pxs. COAT & Chronic Pain For pxs with constant pain, it is agreed that scheduled long-acting opioids with short acting prn opioids are better to decrease pain, dependency and periods of breakthrough pain. Critical for the physician to cautiously increase or decrease dosing. If px has SEs 1 week after increasing dose, then it is too much. When dose exceeds pain control, pxs start exhibiting SEs, unless

opioid sensitive. It is better to start too high than too low to decrease anxiety and pain behaviors due to inadequate analgesia. Is an excellent marker for dose titration and should be monitored routinely, including px education to notify MD if they do develop SEs. Also decreases central sensitization when decreasing pain before it starts Px should sign a contract re: informed consent & their responsibilities for tx. Should understand that care may be terminated if non-compliant. COAT & Chronic Pain

COAT & Chronic Pain Long acting pain control Pain course w/o meds COAT & Chronic Pain Breakthrough/ prn Medication Breakthrough/ Breakthrough/ prn Medication prn Medication Long acting pain control Pain course w/o meds

Opioids: Compliance Monitoring Monitoring also includes ongoing assessment of patient compliance with the controlled prescribing practice of the physician. -CBME Urine drug screens are recommended. Utilization of a single prescribing physician and a single pharmacy is advised. The Colorado Electronic Prescription Drug Monitoring Program COAT & Chronic Pain

Watch for signs of noncompliance with opioid therapy. Unexpected results on tox screens Frequent requests for dose increases Concurrent use of nonprescribed psychoactive substances Failure to follow dosing schedule Failure to adhere to concurrently recommended txs Frequently reported lost prescriptions or meds Frequent ER visits for opioid therapy Missed f/u visits

Frequent extra appointments Prescriptions from a 2nd provider Tampering with prescriptions COAT & Chronic Pain Dosing Titration is generally accomplished by increasing or decreasing the next total daily dose by - the previous dose. Each dose of rapid acting q 4-6h prn opioids should be given at 10% of the pxs daily baseline opioid dose. Or 40-60% of total daily dose. COAT & Chronic Pain Dosing If px is inpatient can convert 75% of previous

opioid dose to long-acting with 25% short acting due to incomplete cross-tolerance. If outpatient, convert 50% of previous opioid dose to long-acting with 50% short acting. For example: px is on 20mg of hydrocodone q6h (80mg/day), conversion dose of hydro- to oxycodone is 1:1, prescribe 20mg of oxycodone q12h and 10mg hydrocodone q6h prn. tramadol Not a true opioid, but a weak opioid agonist. Great 1st line medication for mild/mod pain,

especially in the elderly due to lower SE profile. Dose: 25-50mg Q4-6h (max dose 400mg/day) Also norepi- & serotonin reuptake inhibitor. Analgesic effect not well understood. Start with 25mg/day and titrate up q3 days to 25mg qid Then start 50mg/day & repeat Then start 100mg/day & repeat up to 100mg qid Onset: 60 min life: 7 hours Doses greater than 400mg/day associated

with seizures. acetaminophen/hydrocodone 1st line opioid. Dose: 5-10mg q 4-6h (max dose 4g/day of acetaminophen) Is schedule III with proposed less abuse potential can write 2 refills and see 3 months later. Preferably prescribe 10/325 tablets, instead of 5/325, as 10s can be split in half and have less

acetaminophen. Onset: 10-30 min life: 3.8 hours oxycodone 1st line long-acting opioid. Dose: 10-160mg BID (long-acting/-contin) or 1030mg q4h (short acting/-codone). IR form is a good breakthrough medication, if Norco insufficient. 5mg q6h for OxyIR

max dose 4g/day of acetaminophen Onset: 40 min (CR) & 10-15 min (IR) life: 4.5 hours (CR) & 3.2 hours (IR) methadone Synthetic opioid. Has NMDA receptor blocking action which may reduce central sensitization and opioid tolerance. Seems to have better neuropathic pain reducing properties than other opioids Better choice in high abuse potential patients, but still can be abused! Dose: Initially, 2.5-10mg q6h prn, then after 6 days split average daily dose to BID scheduled.

Onset: 30-60 min life: 7 hours-5 days! 20-120mg/day for dependency tx Only increase dose at least every 5 days Less sedation & N/V than classic opioids. Still has equivalent respiratory depressive effects & constipation. fentanyl patch

If px tolerating and stable on oxy-CR, can switch to a 72-hour patch for convenience, or increasing compliance. Dose: 25-100mcg/h q 72 hours Onset: steady state at 24h If switching to fentanyl, prescriber should give normal dose of previous long-acting opioid for 1st 24hrs. life: 17 hours SEs: watch for skin reaction/ulceration (3-10%).

Avoid in liver or kidney disease. Avoid heating sources, as can increase release of fentanyl. Patch Dose codeine oxy-/hydrocodone morphine hydromorphone 25 mcg/hr 150-447mg/day 22.5-67mg/day 45-134mg/day 5.6-17mg/day

50 mcg/hr 448-747mg/day 67.5-112mg/day 135-224mg/day 17.1-28mg/day 75 mcg/hr 748-1047mg/day 112.5-157mg/day 225-314mg/day 28.1-39mg/day hydoxyzine Antihistamine that potentiates analgesic

effects of opioids, as well as having intrinsic analgesic, anxiolytic and anti-nausea effects. Dose: 25-50mg TID-QID Unknown mechanism Can dose to give with opioids, like Norco. If sedated, switch to 10mg TID-QID. Onset: 15-30 min life: 3 hours SEs: chest tightness (may be pleurisy from dry mucus membranes), tremor/convulsions,

dry mouth. lidocaine patch Can be great for focal superficial, especially neuropathic, pain. Dose: 1-3 patches for 12 hours on and 12 hours off, daily. Approved for post-herpetic neuralgia. One 12 hour patch contains 700mg of lidocaine (50mg/gram)

Onset: peaks at 12 hours life: 81-149 min SEs: watch for skin reaction/ulceration. Avoid in liver disease and non-intact skin Benzodiazepines Benzos are the only class of drug that the withdrawal symptoms are the same symptoms the drug is designed to treat. If someone is tolerant and trying to get off of it, they will have anxiety, palpitations & a jittery feeling purely from withdrawal. Not a psychologic disorder. Anti-convulsants

Older antiepileptic drugs have severe SEs (hepatotoxicity, hematologic effects, etc) and require frequent monitoring. Newer agents have been shown to have good results treating neuropathic pain, sometimes off-label. Used more with HAs (tegretol, topamax, depakote) Tegretol FDA approved for migraines. pregabalin Arguably 1st line for neuropathic pain. FDA approved for post-herpetic neuralgia, diabetic peripheral neuropathy & the first drug approved for

fibromyalgia. Off label for neuropathic pain, but approved in Europe. Less reports of lethargy & dizziness than with gabapentin, but can cause liver damage and true weight gain. No intrinsic activity If failed gabapentin trial, can still try Lyrica. Modulates calcium voltage gated channels, decreasing release of excitatory neurotransmitters. Via alpha-2-delta ligand agonist activity (like gabapentin) Dose: 75mg BID (unless sensitive, use 50mg BID) If no improvement after 3 days, stop it.

If some improvement, double it (300mg BID is max dose). Onset: <60 min life: 6.3 hours, steady state in 24-48 hours gabapentin Older, cheaper and effective for neuropathic pain. Off label for a number of neuropathic pain conditions. Modulates calcium voltage gated channels, decreasing release of excitatory neurotransmitters.

Dose: 300mg daily to 1600mg TID Increase dose by 300mg Q 3 days as outpx. Via alpha-2-delta ligand agonist activity (like gabapentin) Daily in inpx setting. If no effect at 300mg TID, stop it. life: 5-7 hours SEs: dizziness, lethargy, tremors & dysmetria in elderly.

Initial mild SEs may resolve in 2-3 d. Wait before stopping or increasing. Antispasmodics Mechanism of action of muscle relaxers is unknown Sedation? Treat muscle or nerve spasms. Works for neuropathic pain and myofascial pain with spasms. baclofen

GABA derivative. Appears to primarily inhibit spinal efferent & afferent pathways by functioning as an inhibitory neurotransmitter. The primary site of action is the spinal cord, where baclofen also reduces the release of excitatory neurotransmitters. Dose: 5mg TID Can increase by 5mg/dose Q3 days Max dose 80 mg/day Onset: life: 2.5-4 hours SEs: hypotonia, drowsiness, hypotension tizanidine

Centrally acting alpha blocker Dose: 4-36 mg/day Exact mechanism is unknown. Can increase in 2-4mg increments Q 6-8 hours for optimum effect. T max: 1.5 hours life: 2.5 hours SEs: hypotension, impotence, drowsiness, orthostatic hypotension. clonidine

Can be used for spasticity, but great for new-onset CRPS, especially in children. 1st line for opioid withdrawal sxs. Stuffy nose, N/V/D, bone aches (like a bad flu). Dose: 0.1-0.3mg BID for withdrawal 0.1-0.3mg QHS for hot flashes perimenopausal women.

Onset: 30-60 min life: 12-16 hours SEs: hypotension, impotence, drowsiness, orthostatic hypotension. Tricyclic Antidepressants Older antidepressants Have serotonergic > noradrenergic effects and all have antihistaminergic effects. Also antagonize Na channels, alpha-2 & H1 receptors All are a little distinct from each other. TCAs dont work for pain until 7-14 days, but work for sleep immediately & depression in up to 1 month.

All should be given at 25-100 mg QHS Except for desipramine Except desipramine which is BID Dangerous at high doses Can cause irreversible liver necrosis and may be a poor choice for severely depressed. amitriptyline

Large muscarinic effects (dry mouth, sedation, orthostatics). Has the highest incidence of SEs than other TCAs discussed. Dose: 25-100mg QHS life: 10-28 hours SEs: weight gain due to increased appetite doxepin Accomplishes what amitriptyline does with fewer SEs. Dose: 25-100mg QHS life: 8-24 hours desipramine

Has the least anticholinergic and sedative effects of the 1st generation TCAs. Has similar analgesic effects. Only TCA that selectively block norepinephrine reuptake > serotonin. Dose: 10-50 mg BID Onset: 28-31 hours trazodone A heterocyclic antidepressant (4 rings) Great for sleep, as well as having some analgesic effects (less than TCAs, however).

Serotonin reuptake inhibitor Shorter life than other TCAs resulting in less daytime sleepiness. Dose: 25-100mg QHS life: biphasic 3-6 hours & 5-9 hours SEs: lower anticholinergic profile than TCAs. Can cause priapism (less likely to prescribe to men), and up to 30% have vivid dreams that may be tolerated. Sleep Medications Stage III & IV sleep are restorative. Benzos

of sleep. and opioids can both decrease theses stages Non-benzos dont. Sleep is crucial to chronic pain management. Need to find if trouble falling and/or staying asleep to prescribe right meds. Pain or anxiety a factor? If pain, use a TCA and can use ambien/flexeril combinations. Anxiety might benefit from clonazepam, which affects the sleep cycle the least of the benzodiazepines and has a

convenient 8hr half-life. Sleep Medications If mild insomnia use over-the-counter supplements: 5-HTP at 50-100mg QHS. Crosses the BBB and converted to serotonin. Valerian Root at 400-800mg QHS Has a mild serotonin, norepi- and dopamine reuptake blocker. Melatonin:

a hormone that is good for jet-lag. Take for 3 days before a trip at the time you will be going to sleep. zolpidem Non-benzodiazepine hypnotic Classic medication for trouble falling, not staying asleep

Interacts with GABA-benzodiazepine complex to facilitate GABA transmission. Quickly metabolized with least amount of am sedation. Dose: 5-10mg QHS life: 2.6 hours (CR has a delayed release) SEs: sleep walking and driving. Do not give to pxs with hx of sleep walking and advise px to monitor. clonazepam

Benzodiazepine with least effect on decreasing Stage III & IV sleep. temazepam, diazepam, lorazepam & triazolam are worse. Better for pxs with frequent sleep interruptions or with anxiety component. Dose: 0.5-2.5mg QHS T max: 1-4 hours life: 30-40 hours SEs: Hepatotoxicity. Monitor LFTs. eszopiclone New longer acting non-benzodiazepine hypnotic

Interacts with GABA-benzodiazepine complex to facilitate GABA transmission. FDA approved for long-term management of insomnia. Dose: 1-3mg QHS life: 6 hours cyclobenzaprine Is a actually a TCA, but has different effects Is also a serotonin reuptake blocker that helps deepen sleep. Dose: 10 mg QHS initially for sleep. Onset: 1 hour

life: 1-3 days Summary Chronic Pain is persistent pain that no longer serves a purpose. It is a complicated entity that is intimately linked to psychological well-being, sleep patterns, function & relationships. The bio-psycho-social model of diagnosis and treatment is the most effective means of treatment and involves a multidisciplinary team approach. Medications are only a small part of treating chronic pain and should be used with caution with appropriate monitoring and follow-up. The goal is not to eliminate pain, but to empower the patient to be in charge of their pain so that they may lead a full and active life.

Bilbliography Video Clip References 1. Kandel ER, Schwartz JH, Jessell TM, editors. Principles of Neural Science (Fourth Edition). New York: McGraw Hill (Health Professions Division). 2000;472491. 2. Millan MJ. Progress in Neurobiology 1999;57:1164. 3. Dickenson AH. Brit J Anaesthesia 1995;75:193200. 4. Suzuki R and Dickenson AH. Neuroreport 2000;11:R1721. 5. Waxman S. Pain 1999;6:S133140. Bilbliography

Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med 2003; 349:1943-1953. Bruera E, Macmillan K, Hanson K, et al. The cognitive effects of the administration of narcotic analgesics in patients with cancer pain. Pain 1989; 39:13-16 Braddom R. Physical Medicine & Rehabilitation 3rd Edition. pgs 952-981. 2007. Saunders Elsevier. Philadelphia, PA.

Chabal C, et al. Narcotics for chronic pain. Yes or no? A useless dichotomy. APS Journal 1992; 1(4):276-281. Ciccone DS, Just N, Bandilla EB, et al. Psychological correlates of opioid use in patients with chronic nonmalignant pain: a preliminary test of the downhill spiral hypothesis. J Pain Symptom Manage 2000; 20:180192. DeLisa J. Physical Medicine & Rehabilitation Principles and Practice. pgs. 493-518 & 361-363. 2005. Lippincott Williams & Wilkins. Philadelphia, PA. Fishbain DA, Cutler RB, Rosomoff HL, et al. Are opioid dependent/tolerant patients impaired in driving-related skills? A structured evidence-based review. J Pain Symptom Manage 2003; 25(6):559-577. Haythornthwaite JA, Menefee LA, Quatrano-Piacentini AL, et al. Outcome of chronic opioid therapy for noncancer pain. J Pain Symptom Manage 1998; 15:185-194. Katz N, Fanciullo G, Role of urine toxicology testing in the management of chronic opioid therapy. Clin J Pain 2002; 18:S76-S82. Max MB, et al. Efficacy of desipramine in painful diabetic neuropathy: a placebo controlled trial. Pain 1991; 45:39. Stambaugh JE. Pharmacokinetics and mechanisms of action of analgesics in clinical pain. J Clin Pharmacol 1981; 21:S295-S298. U.S. Department of Health and Human Services. Acute pain management: operative or medical procedures and trauma. Clinical Practice Guidelines Feb 1992. Williams GW. Identifying appropriate patients for NSAIDS. Sept. 2007. Zacny JP. A review of the effects of opioids on psychomotor and cognitive functioning in humans. Exp Clin Psychopharmacol 1995; 3:432-466. Special Thanks to Dr. James Gruft!

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