PRESCRIPTIONS FOR PUISSANT PERPETUAL PAIN
| NEUROPATHIC PAIN— Pamela P. Palmer, MD, Professor of Anesthesia, University of California, San Francisco,
Medical Center, and Director, UCSF Pain Management Center, San Francisco
|
| Introduction: neuropathic pain also called “nerve-injury pain,” because it represents injury of nervous system itself,
which erroneously keeps sending messages to brain that “essentially are worthless, as there’s no tissue injury ongoing”;
nerves do not heal well; neuropathic pain often difficult to discriminate from other types of pain; examples of
neuropathic pain include diabetic neuropathy and postherpetic neuralgia
|
| Characteristics of neuropathic pain: lancinating, “electrical-shooting” sensation; burning; allodynia (pain response
to nonpainful stimulus); hyperalgesia (increased pain in response to lightly painful stimulus); hyperpathia (if area
lightly stroked, it does not hurt, but if same stroking continues, patient experiences sudden excruciating pain)
|
| Causes of neuropathic pain: trauma; metabolic problems, eg, diabetes; ischemia; toxins; compression; infections; assault
on nervous system leads to excitation of peripheral nerves, which leads to excitation of spinal cord and brain,
resulting in spontaneous and evoked pain; most of neuropathic pain due to injury in peripheral nervous system
|
| Medicines that help neuropathic pain
|
 | Anticonvulsants: carbamazepine (Tegretol)—serendipitously found to treat neuropathic pain; requires monitoring of
blood levels due to risk for aplastic anemia; one third of people who take it have gastric irritation and nausea;
phenytoin (Dilantin)—not used much any more (along with carbamazepine) due to side effects; gabapentin
(Neurontin)—“works fairly well for a number of neuropathic-pain conditions”; blocks N-type calcium channels; if
gabapentin does not work, does not mean patient’s pain not neuropathic; consider switching to sodium channel
blocker; start on low dose, usually 300 mg at night, work up to 300 mg tid; if patient very drug sensitive, start at
100 mg at night; maximum dose 4800 mg/day; topiramate (Topamax)—“many people get dopey on it” (ie, develop
psychomotor slowing and difficulty with concentration and speech or language problems, or develop somnolence
or fatigue); start low (15-mg sprinkle capsule available) with qhs dosing; go to bid dosing only after
proven that patient can tolerate drug without many side effects; maximum dose 400 mg/day, all at night or bid;
causes renal stones in rare cases; may cause weight loss (“which most patients love”), but sometimes causes too
much weight loss; lamotrigine (Lamictal)—can be combined with other anticonvulsants if first anticonvulsant not
effective; reduce first anticonvulsant to half dose, then add half dose of lamotrigine; watch for rash, which occurs
in 5% to 10% of patients; if rash occurs, lamotrigine must be stopped, and patient can never take it again; if medication
not stopped, rash can become “very nasty”; less sedating than topiramate and does not cause as much
memory impairment as gabapentin; other agents available—levetiracetam (Keppra; minimal side effects); oxcarbazepine
(Trileptal); mexiletine (Mexitil; actually antiarrhythmic but included here because it is sodium channel
blocker and works for neuropathic pain; maximum dose 300 mg tid); tiagabine (Gabitril); zonisamide (Zonegran)
|
| Antidepressants: tricyclics work better than selective serotonin reuptake inhibitors (SSRIs); amitriptyline more sedating
than nortriptyline (may be more beneficial for patients who cannot sleep)
|
| Opiates: “not that effective as a sole agent”; combine with anticonvulsant, antidepressant, or antiarrhythmic to get
full efficacy
|
| Local anesthetics: lidocaine patch (Lidoderm) approved by Food and Drug Administration (FDA) only for postherpetic
neuralgia, but also works on complex regional pain syndromes where pain superficial and localized; if patient
has severe allodynia and placement and removal of lidocaine patch likely to be irritating, bupivacaine cream can be
compounded by pharmacist; patient can apply cream in manner least likely to be painful
|
| Other methods of pain control: if above methods do not work, probably best to refer patient to pain management
center; spinal cord stimulator—works best on pain in extremity refractory to all other treatment; intrathecal pump—
not first-line therapy; used to treat refractory pain; formerly, morphine only substance used in pumps, but now
known that hydromorphone works better and has fewer side effects; medication combinations (eg, clonidine and
opioid) can be used
|
| What’s new? ziconotide intrathecal infusion (Prialt)—recently approved by FDA for use in intrathecal pump; not easy to
use; therapeutic window very small, so problems can arise; appears to have minimal development of tolerance; duloxetine
(Cymbalta)—monoamine uptake blocker; seems to work better than other monoamine uptake blockers; approved for
treatment of depression and diabetic neuropathy; pregabalin (Lyrica)—N-type calcium channel blocker; approved by
FDA, but not yet available in United States; thalidomide—still available, but “you must jump through a million hoops to
actually get it for your patient”; cytokine inhibitor that has efficacy in neuropathic pain; can cause peripheral neuropathy;
consider it only in patients not pregnant and not contemplating pregnancy; felbamate—anticonvulsant with N-methyl-D-aspartate
(NMDA) receptor inhibition; ketamine—blocks NMDA receptor on wide-dynamic-range (WDR)
neurons, blocks calcium entry, and blocks plasticity in spinal cord; can be compounded for oral use; use low doses, ie, 50
to 100 mg/day; high-dose capsaicin patch—being tested for treatment of neuropathic pain; tramadol (Ultram)—“weak-
acting” opiate combined with monoamine uptake blocker
|
| Summary: try medications one at a time, but recognize that low doses of several agents may need to be combined to
obtain pain relief; neuropathic pain difficult to treat, but new developments in last 5 yr optimistic; central nervous
system plasticity can result in altered nociceptive pathways and may require altered approach to treatment; oral medications
“can be wonderful” but can produce significant side effects; if that happens, refer patient to pain management
center
|
| MIGRAINE AND DAILY CLUSTER HEADACHE —Lawrence Robbins, MD, Assistant Professor of Neurology,
Rush Medical College, Chicago, and Proprietor, Robbins Headache Clinic, Northbrook, Illinois
|
| Introduction: 95% of people who have headaches have migraine and/or chronic daily headache, and “virtually all
chronic, long-standing headaches fall into those categories”; traditionally, pathophysiology focused on serotonin,
but recently, other neurotransmitters, including nitric oxide, shown to play role
|
| Diagnosis: migraine—speaker defines as chronic recurring headache, moderate to severe, brought on by certain triggers
(different from International Headache Society classification); most common triggers stress, hormones, and
weather; associated features such as nausea, photophobia, sonophobia, and dizziness help to make diagnosis, but
not required; ≈90% have associated features with migraine; tends to be familial; ratio of women to men 3:1 after 10
yr of age; estimated that 1% of 6-year-olds and 4% of 10-year-olds experience migraine; chronic daily headache—
defined as at least 15 days of headache for at least 3 mo; ≈3% of population has chronic daily headaches (across all
countries and races; unlike migraine, which tends to differ from race to race); people who have chronic daily headache
24 hr/day, 7 days/wk may overuse medications; in speaker’s study, only 46% of patients with chronic daily
headaches did well over long term; more migraineurs respond to preventives
|
| Head scans: magnetic resonance imaging (MRI) usually not necessary, but often done for legal protection of clinician;
speaker requests MRI in patients with new-onset headaches (especially adolescents and children) and in patients
with major change in neurologic or mental status; overall, speaker orders MRI on ≈20% of his patients (and
some bring scans with them from previous physician)
|
| Pearl: always legitimize headache as medical illness; many patients have psychologic comorbidities, but those comorbidities
not shared; if headache not legitimized as its own entity, patient may quit treatment
|
| More pearls: balance headache and medication (avoid overmedication); many patients have several varieties of headache
and tend to take different over-the-counter (OTC) medications for each; establish reasonable goals, encourage
patient to accept 50% improvement (“90% or 100% would be great, but it’s not always possible”); on first visit—
take history and perform physical examination; get idea of what medications might help and record them in patient’s
chart, so if patient calls later to say current medication not working, chart will indicate which medication to
try next; comorbidities can help determine which medications to use
|
| Medications: start with low doses of any medications given to headache patients; use analgesic doses of antidepressants,
not antidepressant doses; weight gain “is a big issue” with patients; in middle-aged people, weight gain may
lead to noncompliance; help patient to set reasonable goals and accept less than perfect outcome (“acceptance
doesn’t mean resignation”)
|
| Triggers: stress—“not necessarily bad stress or good stress; more daily hassles; when people with headaches have increase
in daily hassles, headaches increase in ≈50%; that goes for adolescents too”; weather—migraine triggered by
weather often leads to misdiagnosis of sinus headache; studies of people told they had chronic sinus headache found
≈95% of headaches migraine; headache may worsen “a little bit” with nasal stuffiness that accompanies allergies,
but often when allergies successfully treated, headaches remain same; hormones—migraine may accompany changes
in hormone levels with menstruation, pregnancy, breast-feeding, and menopause; menstrual migraines tend to last
longer, be more severe, and be difficult to treat in some women; other triggers—missing meals; sunlight or fluorescent
lights; migraine caused by fluorescent lights causes many lost days of school in adolescents; also, schools that
start earlier in morning find more students absent with migraine; sleep—undersleeping more problematic in younger
patients, oversleeping more problematic in adults; foods—tend to be overdiagnosed as cause of headaches (speaker
plugs his book, Headache 2005, available free at headachedrugs.com, which contains list of food triggers, among
other things); caffeine—“double-edged sword” that in small amounts can help headache, but too much causes rebound
headache; great interperson variability on how much caffeine can be tolerated; speaker recommends limiting
caffeine to <150 to 200 mg/day (typical cup of brewed coffee has 100 to 150 mg; specialty coffees range from 200 to
400 mg/cup; if tea has caffeine, usually ≈30 mg per cup; soft drinks have 40 to 50 mg/can, but some have much
more; OTC headache remedies have from 32 to 65 mg/tablet)
|
| What else can be done: exercise; “anything that promotes relaxation”; biofeedback greatly underutilized; psychotherapy;
trigger-point injections or physical therapy if headache associated with neck pain; acupuncture not helpful
|
| Comorbidities: try to minimize medications by using same drug to treat headache and comorbidity whenever possible;
anxiety—most common headache comorbidity, usually generalized anxiety disorder, but sometimes obsessive-
compulsive disorder or panic disorder; depression—study found 8.6% of migraineurs to have bipolar disorder;
avoid treating with antidepressant without mood stabilizer (“the clinical stakes for missing bipolar are enormous”);
insomnia—relatively common in headache population; attention-deficit disorder (ADD)—some medications, eg, Adderall
(amphetamine mixture) can help ADD and headache; personality disorders—usually constitute small percentage
of patients in practice, but can drain enormous amounts of time and energy from clinician and staff; speaker posits
that most clinicians do not understand best way to approach people with personality disorders; long-term goals necessary;
use dialectic or cognitive behavior therapy in addition to medications; irritable bowel syndrome—alosetron
(Lotronex) and mirtazapine (Remeron) new drugs that may help; fibromyalgia—some medications used for it can
also help headache
|
| Prevention: most patients with migraine do not need daily prevention medicine; triptans abort migraine quickly if
taken before allodynia starts; triptans are a little different from each other, so if one does not work, try another; triptans
include sumatriptan (Imitrex), rizatriptan (Maxalt), eletriptan (Relpax), and zolmitriptan (Zomig)
|
| Final remarks: by time people consult physician, they have tried many things; opioids can be used (cautiously); antiemetic
may help migraineurs to stay out of emergency department; divalproex (Depakote) and topiramate (Topamax) approved
by FDA for migraine prevention; nonsteroidal anti-inflammatory drugs (NSAIDs) might work as daily preventive in
some; tricyclic antidepressants sometimes work for prevention; several double-blind studies found that Petadolex (standardized
patented extract of butterbur root) works, and is only herbal known to work; speaker recommends avoiding St.
John’s wort because of its interactions with other drugs
|
Educational Objectives
| The goal of this program is to educate the listener about treating neuropathic pain and migraine and chronic daily headaches. After
hearing and assimilating this program, the clinician will be better able to:
|
| 1. Describe the characteristics of neuropathic pain.
|
| 2. State the causes of neuropathic pain.
|
| 3. Discuss medications and other treatment options for neuropathic pain.
|
| 4. Distinguish migraine and chronic daily headache from other types of headaches.
|
| 5. Summarize the options for prevention and treatment of migraine and chronic daily headache.
|
Discussed on This Program
Almotriptan maleate [Axert]
Alosetron hydrochloride [Lotronex]
Amitriptyline hydrochloride [Elavil]
Amphetamine and dextroamphetamine [Adderall, Adderall XR]
Aspirin, acetaminophen, and caffeine [Excedrin Extra Strength, Excedrin Migraine, Goody’s Extra Strength Headache Powder,
Vanquish Tablets]
Bupivacaine hydrochloride [Marcaine, Sensorcaine]
Butalbital, aspirin, and caffeine [Fiorinal, Fiortal]
Butterbur (Petasites hybridus), standardized patented extract [Petadolex]
Capsaicin (several formulations and trade names)
Carbamazepine [Tegretol, others]
Clonidine hydrochloride [Duraclon]
Dexamethasone [Decadron, others]
Dextromethorphan hydrobromide [Robitussin DM, others]
Divalproex sodium [Depakote]
Duloxetine [Cymbalta]
Eletriptan hydrobromide [Relpax]
Ergotamine tartrate and caffeine [Cafergot, others]
Felbamate [Felbatol]
Fentanyl [Sublimaze]
Frovatriptan succinate [Frova]
Gabapentin [Neurontin]
Hydrocodone bitatrate and acetaminophen [Norco, others]
Hydromorphone hydrochloride [Dilaudid]
Ibuprofen [Advil, Motrin, others]
Isometheptene mucate/dichloral phenazone/acetaminophen [Midrin, others]
Ketamine hydrochloride [Ketalar]
Ketorolac tromethamine [Toradol]
Lamotrigine [Lamictal]
Levetiracetam [Keppra]
Lidocaine hydrochloride [several formulations and trade names]
Meperidine hydrochloride [Demerol]
Methadone hydrochloride [Dolophine, Methadose]
Methylphenidate hydrochloride (several trade names)
Metoclopramide [Reglan, others]
Mexiletine hydrochloride [Mexitil]
Mirtazapine [Remeron]
Modafinil [Provigil]
Morphine sulfate (several trade names)
Naproxen (Aleve, others)
Naratriptan hydrochloride (Amerge)
Nortriptyline hydrochloride [Aventyl, Pamelor]
Ondansetron hydrochloride [Zofran]
Oxcarbazepine [Trileptal]
Oxycodone HCl and oxycodone terephthalate [Percodan, Percodan-Demi, Roxiprin]
Phenytoin sodium [Dilantin]
Prednisone (several formulations and trade names)
Pregabalin [Lyrica]
Protriptyline hydrochloride [Vivactil]
Rizatriptan benzoate [Maxalt, Maxalt-MLT]
Sumatriptan succinate [Imitrex]
Tegaserod maleate [Zelnorm]
Thalidomide [Thalomid]
Tiagabine hydrochloride [Gabitril]
Topiramate [Topamax]
Tramadol hydrochloride [Ultram]
Venlafaxine [Effexor, Effexor XR]
Ziconotide intrathecal infusion (SNX-111) [Prialt]
Zolmitriptan [Zomig, Zomig-ZMT]
Zonisamide [Zonegran]
Suggested Reading
Blackburn-Munro G et al: Antiepileptics and the treatment of neuropathic pain: evidence from animal models. Curr Pharm
Des 11:2961, 2005; Coderre TJ et al: Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of
glutamate. J Neurochem 94:1131, 2005; Coeytaux RR et al: A randomized, controlled trial of acupuncture for chronic daily
headache. Headache 45:1113, 2005; Coluzzi F et al: Mechanism-based treatment in chronic neuropathic pain: the role of antidepressants.
Curr Pharm Des 11:2945, 2005; Diener HC: Headache. Curr Opin Neurol 18:279, 2005; Irving GA: Contemporary
assessment and management of neuropathic pain. Neurology 64:S21, 2005; Kalso E: Sodium channel blockers in neuropathic
pain. Curr Pharm Des 11:3005, 2005; Martin VT et al: The predictive value of abbreviated migraine diagnostic criteria. Headache
45:1102, 2005; Mattia C: Coping with neuropathic pain: do we need more selective analgesic drugs? Curr Pharm Des
11:2941, 2005; May A: The role of imaging in the pathophysiology and diagnosis of headache. Curr Opin Neurol 18:293, 2005;
Olesen J: The International Classification of Headache Disorders, 2nd edition: application to practice. Funct Neurol 20:61, 2005;
Przewlocki R et al: Opioids in neuropathic pain. Curr Pharm Des 11:3013, 2005; Robbins L: Headache 2005. Available at
headachedrugs.com. Accessed October 11, 2005. Sawynok J: Topical analgesics in neuropathic pain. Curr Pharm Des 11:2995,
2005; Tully CM et al: Principles of pain management II: agents for neuropathic pain. Conn Med 69:335, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the following has been disclosed: Dr. Palmer is on the Speakers’ Bureau or receives honoraria from Medtronic and
Pfizer, Inc. She also discussed the investigational/off-label use of anticonvulsants. Dr. Robbins is on the Speakers’
Bureau for Glaxo and Pfizer, Inc.
Dr. Palmer was recorded at Pain Management and End-of-Life Care, presented June 9-10, 2005, in San Francisco and
sponsored by the University of California, San Francisco, Schools of Medicine, Nursing, and Pharmacy. Dr. Robbins
spoke at The 10th Annual Psychopharmacology Update, held February 17-19, 2005, in Las Vegas and sponsored by the
American Psychiatric Association and the Nevada Psychiatric Association. The Audio-Digest Foundation thanks the
speakers and the sponsors for their cooperation in the production of this program.
|
