PAIN MANAGEMENT
| OVERVIEW OF PAIN MANAGEMENT —Mark S. Wallace, MD, Professor of Clinical Anesthesiology, and Director,
UCSD Center for Pain and Palliative Medicine, University of California, San Diego, School of Medicine, La Jolla, CA
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| Assessing pain: identify and treat underlying condition (which may resolve pain without further treatment); identify comorbid
conditions, especially psychologic comorbidities; assess psychosocial factors; assess functional status; set
goals of therapy; develop targeted plan; determine when to refer to specialist
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 | Measuring pain: several scales available; speaker prefers Likert 11-point scale, which has been studied extensively; absolute
pain score not as significant as patient’s assessment of improvement; eg, patients report that, even if initial score
on Likert scale 8 or 9, 2-point improvement (equivalent to 30% reduction in pain) results in increase in their overall
satisfaction; ask patients what their goals are and “what kind of pain score they can live with”
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| Approach to treatment: diagnose and treat underlying condition; “early treatment of pain will prevent chronic pain”; improve
physical functioning; reduce psychologic distress; improve overall quality of life; treat sleep disturbances (“a major
problem with pain patients”; patients with sleep disturbance have increased daytime pain); determine rehabilitation needs
and refer to occupational or physical therapy as appropriate
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| Pain-treatment continuum: starts with least invasive therapies and progresses to most invasive, although efficacy not
related to degree of invasiveness (“a lot of patients think that the more invasive it is, the better it is but that’s not
true”)
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| Nonpharmacologic options: include biofeedback, relaxation therapy, physical and occupational therapy, cognitive behavioral
strategies, acupuncture, and transcutaneous electrical nerve stimulation; insurance companies often reluctant to
pay for these therapies; some of these therapies can be administered by nonphysicians
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| Speaker’s thought process for medications and interventional techniques: efficacy—preferably established by multicenter
randomized controlled trials; if study data lacking, what is clinical experience? is treatment widely used? if anecdotally
widely used, what evidence exists for its efficacy? safety—if safety issues minimal, speaker may try therapy,
but if safety issues exist in absence of data to support efficacy, he does not use; ease of use—dosing; titration; drug
interactions; patient acceptability; cost
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| Neuropathic pain: medications approved by Food and Drug Administration (FDA) include lidocaine patch, gabapentin,
pregabalin, duloxetine, and carbamazepine
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| Lidocaine patch: contains lidocaine 5% in pliable transdermal system; FDA has approved use of up to 3 patches applied
once daily directly over painful site; efficacy for postherpetic neuralgia demonstrated in 3 randomized controlled clinical
trials; minimal systemic absorption and few side effects; mechanical barrier decreases allodynia; works by blocking
sodium channels on peripheral nociceptors
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| Gabapentin: anticonvulsant approved by FDA for postherpetic neuralgia; works by modulating N-type calcium channels;
limited intestinal absorption; usually well tolerated and serious adverse effects rare; may cause dizziness and sedation;
no significant drug interactions; peaks in 2 to 3 hr; elimination half-life, 5 to 7 hr; delay in onset of effect, 1 to 3 wk
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| Pregabalin: approved by FDA for postherpetic neuralgia and diabetic peripheral neuropathy; calcium channel modulator;
robust efficacy confirmed in 6 positive trials; reduction in pain within 1 wk in some patients; high responder rates; favorable
safety and tolerability profiles; most common adverse events dizziness and somnolence; linear pharmacokinetics
provide high bioavailability; absorption predictable and consistent
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| Antidepressants: tricyclic antidepressants shown effective; selective serotonin reuptake inhibitors (SSRIs) inconsistent
(“they are great antidepressants, very poor analgesics”); onset of analgesia variable; analgesic effects independent of
antidepressant effects; trials show improvements in insomnia, anxiety, and depression; desipramine and nortriptyline
have fewest adverse effects; onset of action delayed “for weeks”; duloxetine (selective norepinephrine reuptake inhibitor
[SNRI]) shown effective in treating diabetic neuropathic pain in one trial, and onset of action rapid (“probably
within the first week”); venlafaxine, another SNRI, has similar side effect profile to duloxetine, but onset of action delayed
up to 6 wk
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| Opioids: titrate for therapeutic efficacy instead of for adverse events; fixed-dose regimens generally preferred to “as
needed” (prn) regimens; document treatment plan and outcomes; consider use of written opioid care agreement; opioids
can be effective in neuropathic pain; most adverse events can be controlled with appropriate specific management; understand
differences between addiction, tolerance, physical dependence, and pseudoaddiction
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| Interventional therapies: speaker uses same thought process as for medications when determining which interventional
therapies to use; however, difficult to study these techniques, and data from randomized controlled trials limited;
challenges include ethical limitations of blinding surgical techniques and of using placebo that prolongs suffering while
exposing patients to surgical risks, prohibitive costs, difficulty of blinding sham procedures, and difficulty recruiting adequate
numbers of subjects; treatments include epidural steroid injections (several techniques available; wide range of
risks), radiofrequency ablation techniques, sympathetic blockades, and spinal cord stimulation
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| Conclusions: patients must be selected carefully for any form of pain management; all patients should have psychologic
evaluation to ensure that their expectations realistic and compliance likely
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| MANAGING MIGRAINE —James U. Adelman, MD, Associate Clinical Professor of Medicine, Department of Neurology,
University of North Carolina, Chapel Hill, and Staff Neurologist, Headache Wellness Center, Greensboro, NC
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| Introduction: only about one-half of patients with migraine correctly diagnosed; of those diagnosed incorrectly, 42% diagnosed
as having sinus-type headache and 32% as having tension-type headache; survey showed that 94% of patients
who sought treatment in physicians’ offices had migraine (migraine is type of headache that gets severe enough for patients
to seek treatment); although tension-type headache most common in population, it usually responds readily to over-
the-counter analgesics, and patients do not seek physicians’ help
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| What is migraine? currently defined as episodic headache with any type of disability; disability not necessarily absence
from work or school (impaired performance at work or school also qualifies as disability); current approach is to stop individual
headaches and to reduce frequency of headaches; order in which to address problems depends on individual patient’s
circumstances; rather than asking patient how many headaches he or she has per month, speaker asks how many
days per month patient is headache-free (if asked how many headaches per month, patients tend to count only “bad”
headaches, but on further questioning, admit to having some degree of headache almost every day); if patient free of
headache most days, focus therapy on preventing or stopping individual headaches; if patient has headache most days, focus
on reducing frequency
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| Components of treatment: education; behavioral therapy (“which is terribly important”); pharmacologic therapy;
abortive therapy; preventive treatment; stages of migraine include prodrome, aura (in patients who have auras), mild
stage, moderate to severe stage, and postdrome
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| Acute care treatment: “window of opportunity” occurs in first hour after patient senses he or she is getting headache
(prodrome and mild stage); ≈65% of patients report that headache can be prevented with treatment (speaker prefers
nonsteroidal anti-inflammatory drug, “perhaps with metoclopramide”)
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| Aura: unclear whether to treat during aura stage; 2 studies showed that treating with subcutaneous (SQ) sumatriptan and
eletriptan during aura not effective, but in other studies, some patients did benefit from oral triptan during aura; some
patients report that treating too early not effective, so speaker recommends that patient wait until mild stage to take oral
triptan
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| Bottom line: acute care treatment depends on ultimate pain level and on rapidity with which headache develops; if pain
rises to moderate to severe level over 0.5 to 1.5 hr, specific (as opposed to nonspecific) pain medications needed, and
triptans specific
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| Triptans: attack 5HT1B and 1D receptors; because of specificity, side effects fewer; work rapidly and efficiently; SQ
injection—most rapid onset with SQ sumatriptan, available in 6-mg and 4-mg injections; only triptan available in
injectable form; recommended for patients who awaken with headache, nausea, or vomiting; nasal sprays—
sumatriptan available in 20-mg and 5-mg doses; speaker prefers 20-mg dose; zolmitriptan available in 5-mg dose;
oral agents—rapidly dissolving tablets include zolmitriptan (Zomig-ZMT) in 2.5- and 5-mg doses and rizatriptan
(Maxalt-MLT) in 5- and 10-mg doses; all triptans available in oral form that is not rapidly acting; naratriptan and
frovatriptan act slowly, and speaker considers them not very effective
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| Efficacy: assessed as moderate to severe pain reduced to mild or no pain in 2 hr; frovatriptan, 2-hr efficacy ≤40%;
naratriptan, ≈45% to 49%; almotriptan, eletriptan, “old form of” sumatriptan, ≈60%; sumatriptan rapid-release tablets
(RT) ≈70%; “old form of” zolmitriptan, ≈65%; zolmitriptan RT, ≤77%
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| Safety: all products similar; early concern about adverse cardiovascular events not supported by more recent data
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| Preventive treatment: “not as good as the acute care treatment”; consider preventive treatment if headaches occur
more than twice weekly on regular basis; behavioral therapy crucial; components of behavioral therapy include diet,
regulation of circadian rhythms, exercise, elimination of triggers, elimination of overused substances, fun, and relaxation
training
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| Preventive medications: only FDA-approved medications methysergide (no longer available in United States), propranolol,
timolol, valproic acid, and topiramate; other treatments that may be effective include antidepressants, antihypertensives,
neural stabilizers, serotonin antagonists, and alternative therapies; select medication by comorbidity; efficacy
of all agents similar and “unfortunately, not as good as we want it to be”; adverse effects difficult to predict for individual
patients; once-a-day regimens preferred to bid or tid; oral formulations preferred for ease of administration; “costs
can vary tremendously”
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| β-Blockers: all nonsympathomimetic β-blockers equally effective; propranolol most commonly used, but speaker prefers
atenolol (inexpensive; can be given once daily, typically at night; fewer side effects); end point for β-blockers is pulse
rate in low 70s or upper 60s, and dose determined accordingly; in studies, 45% to 60% of patients reported 50% reduction
in headaches
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| Calcium channel blockers: good for cluster headaches, not good for migraine; use doses higher than those for treatment
of hypertension; may be effective if aura prominent feature; in studies, verapamil and amlodipine took up to 3 mo to
achieve effect
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| Tricyclic antidepressants: low doses effective (for amitriptyline, doxepin, and imipramine, 50 mg/day); with amitriptyline
and doxepin, end point is sleep without daytime sedation; side effects with amitriptyline and doxepin include
weight gain; with nortriptyline and imipramine, all side effects less; when using nortriptyline, prescribe by generic
name, which costs ≈$17/mo (brand name [Pamelor] costs $575/mo); desipramine and protriptyline nonsedating and
not associated with weight gain (protriptyline currently available only by brand name [Vivactil])
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| Other antidepressants: SSRIs and bupropion not effective in migraine; venlafaxine effective; in study, patients with anxiety
benefitted from duloxetine; monoamine oxidase inhibitors effective, but have numerous side effects
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| Neural stabilizers: previously called anticonvulsants; divalproex (Depakote) and topiramate FDA-approved; both have
significant side effects, including weight gain, hair loss, and fetal neural tube defects; in study, only 36% of patients responded
to gabapentin
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| Serotonin antagonists: speaker uses cyproheptadine in children; methysergide effective, but no longer available in United
States due to side effect profile
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| Alternative treatments: riboflavin—in small study, 59% of patients responded; magnesium—should be effective;
known that patients with migraine have low levels of magnesium in brain; shown that intravenous magnesium stops
headache; feverfew—effectiveness not clear; coenzyme Q10—effective in some studies; butterbur (Petasites
hybridus)—in study, efficacy ≤71%, but efficacy of placebo 59%; botulinum toxin type A (Botox)—no clinical profile;
anecdotally, some patients respond, others do not; large trial now under way
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| Recommendations: clinicians who do not specialize in headache select amitriptyline, imipramine, or venlafaxine as
first-line medications; speaker recommends using β-blocker second, and prefers atenolol; use neural stabilizer third
(speaker prefers topiramate)
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| Conclusions: episodic headache with any disability (especially nausea and/or photophobia) is migraine; acute care treatment
is race against central sensitization; preventive treatment selected on basis of comorbidity; aggressive treatment
prevents progression to chronic migraine
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Suggested Reading
Adelman JU et al: Comparison of rizatriptan and other triptans on stringent measures of efficacy. Neurology 57:1377,
2001; Adelman JU, Adelman RD: Current options for the prevention and treatment of migraine. Clin Ther 23:772,
2001; Adelman JU, Belsey J: Meta-analysis of oral triptan therapy for migraine: number needed to treat and relative
cost to achieve relief within 2 hours. J Manag Care Pharm 9:45, 2003; Adelman JU, Lewit EJ: Comparative aspects
of triptans in treating migraine. Clin Cornerstone 4:53, 2001; Adelman LC et al: Pharmacoeconomics: the cost of prophylactic
migraine treatments. Headache 44:1050, 2004; Al Malyan M et al: Novel drug delivery systems in pain therapy.
Minerva Anestesiol 73:173, 2007; Backonja MM, Krause SJ: Neuropathic pain questionnaire—short form.
Clin J Pain 19:315, 2003; Boyajian SS: Interventional pain management: an overview for primary care physicians. J
Am Osteopath Assoc 105(Suppl 4):S1, 2005; Brandes JL et al: Sumatriptan-naproxen for acute treatment of migraine:
a randomized trial. JAMA 297:1443, 2007; Emanuel L: Ethics and pain management: an introductory overview. Pain
Med 2:112, 2001; Gallagher RM: Rational integration of pharmacologic, behavioral, and rehabilitation strategies in the
treatment of chronic pain. Am J Phys Med Rehabil 84(3 Suppl):S64, 2005; Grabinsky A: Mechanisms of neural blockade.
Pain Physician 8:411, 2005; Krause SJ, Backonja MM: Development of a neuropathic pain questionnaire. Clin
J Pain 19:306, 2003; Kwong WJ et al: The effect of early intervention with sumatriptan tablets on migraine-associated
productivity loss. J Occup Environ Med 47:1167, 2005; Manchikanti L et al: Evidence-based interventional pain
management: principles, problems, potential and applications. Pain Physician 10:329, 2007; Mannix LK et al: Almotriptan
versus sumatriptan in migraine treatment: direct medical costs of managing adverse chest symptoms. Am J Manag
Care 8(3 Suppl):S94, 2002; Schim JD, Stang P: Overview of pain management. Pain Pract 4(Suppl 1):S4, 2004;
Taylor AP et al: Efficacy of duloxetine as a migraine preventive medication: possible predictors of response in a retrospective
chart review. Headache 47:1200, 2007; Von Seggern RL et al: Efficacy of topiramate in migraine prophylaxis:
a retrospective chart analysis. Headache 42:804, 2002; Wallace M, Yaksh TL: Long-term spinal analgesic
delivery: a review of the preclinical and clinical literature. Reg Anesth Pain Med 25:117, 2000.
Educational Objectives
| The goal of this program is to improve pain management. After hearing and assimilating this program, the clinician
will be better able to:
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| 1. Describe treatment options for chronic pain.
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| 2. Participate in a pain-management team.
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| 3. Discuss the latest definition of migraine.
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| 4. Prevent or stop individual migraine attacks in patients who are headache-free most days.
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| 5. Reduce the frequency of migraine attacks in patients who have a headache most days.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in
health care and not a proprietary business or commercial interest. For this program, the following has been disclosed:
Dr. Wallace is on the Speakers’ Bureau for Pfizer. Dr. Adelman is on the Speakers’ Bureaus for and receives honoraria
from GlaxoSmithKline, Merck, and Ortho-McNeil; he is on the National Advisory Boards of GlaxoSmithKline,
Merck, and AstraZeneca; he provides research for GlaxoSmithKline, Merck, Pfizer, AstraZeneca, Ortho-McNeil, Eisai,
Vernalis, Pozen, and UCB Pharma; and has stock in Johnson & Johnson. The planning committee reported nothing
to disclose.
Acknowledgements
Dr. Wallace was recorded at Pain Management in Women Over the Life Cycle, held April 26-27, 2007, in San Diego,
CA, and sponsored by the University of California, San Diego, School of Medicine. Dr. Adelman was recorded at the
Seventh Annual Augusta Pain and Headache Conference: Managing Difficult Pain and Headache Patients, held May
16-17, 2007, in Augusta, GA, and sponsored by the Walton Pain and Headache Centers at Walton Rehabilitation
Health System, and the Medical College of Georgia, Division of Continuing Education and School of Medicine. The
Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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