Patients with chronic pain have always posed big challenges for neurologists, both in diagnosis and in treatment strategies. Why and how neurologists treat pain, however, is dynamically changing.
The clinical difficulty and emotional drain of treating pain syndromes has been complicated by medical schools and residency programs that traditionally give short shrift to this aspect of neurology practice, and instead, emphasize pain management for oncologists, anesthesiologists, and primary care physicians. The advent of new approaches and medication regimens has changed this picture, however, and neurologists are beginning to play a vital role in managing pain.
"Pain is an event of the nervous system," said Charles Argoff, MD, director of the Cohn Pain Management Center at North Shore University Hospital and an assistant professor of neurology at the New York University School of Medicine. "It's also the most common reason people come to a doctor."
For Argoff, it's second nature for neurologists to take care of people with a variety of painful conditions. "We're not talking about being in charge of disease modification or prescribing autoimmune therapy for rheumatoid arthritis," he explained, "but I'd guess that in 5 or 10 years there will be neuropathic mechanisms attributed to the chronic pain associated with osteoarthritis and other conditions."
Indeed, Argoff suspects that if any pain continues long enough, it will lead to changes in the CNS similar to those occurring in neuropathic pain, although such changes have not yet been defined. "A neurologist would want to be involved because he or she has knowledge of how a typical inflammatory pain state can transform into a more chronic, smoldering, less inflammatory state, which might benefit from a different type of therapy," Argoff explained.
Pain management has gained greater attention partly because, as the population ages, pain syndromes are simply more prevalent.1 Chronic pain is now reported in roughly 20% of visits to primary care physicians2; moreover, diseases such as type 2 diabetes, which is associated with peripheral neuropathy, are increasing in a population that is more sedentary and obese.3
The American Academy of Neurology (AAN) published a position statement in 2001 stating that neurologists have a "special responsibility" to pain patients because of the neurologists' familiarity with the nervous system and their experience in providing sophisticated pharmacotherapy for a variety of disorders.4 The paper pointed out, however, that some neurologists avoid or undertreat patients with chronic pain for a variety of reasons. Among these are unfamiliarity with treatments and outcome measures, lack of support from other caregivers, reimbursement barriers, and legal concerns.
Noting that appropriate pain assessment, management, and patient education are now criteria for US hospital accreditation,5 the AAN lists neurologists' ethical obligations to their patients. These include becoming educated about chronic pain and how to manage it, ensuring that patients are properly evaluated for remediable medical or psychiatric causes, considering alternative methods of analgesia, monitoring both analgesic and side effects of drugs, and referring patients to expert multidisciplinary programs when indicated.
On a day-to-day basis, neurologists typically deal with pain of 3 broad types--headache, spinal, and peripheral nerve--according to J. D. Bartleson, MD, associate professor of neurology at the Mayo Clinic in Rochester, Minn. Bartleson, who holds a subspecialty certification in pain medicine from the American Anesthesiology Association, added that of these, headaches are the most common complaint and include migraines, trigeminal neuralgia, and other types.
"Most headache and back pains are episodic, and the patient may need medication for just a few days," Bartleson said, noting that in intermittent but severe cases opioids may be indicated. For patients with more frequent headaches, or with neuropathic conditions, neurologists have had some success with anticonvulsants such as gabapentin(Drug information on gabapentin) (Neurontin, Parke-Davis), as well as with tricyclic antidepressants.
Additional causes of headache pain include other cranial neuralgias (eg, glossopharyngeal, occipital); stroke; intracerebral hemorrhage; subarachnoid hemorrhage; cerebral venous thrombosis; carotid and vertebral artery dissection; and certain mitochondrial disorders.6 These, too, may be treated with anticonvulsants or antidepressants, according to Jeffrey Chavin, MD, assistant professor of neurology at Tufts New England Medical Center in Boston.
Bartleson noted that less traditional approaches to headache pain can also show benefit; these include biofeedback and use of botulinum toxin. But one of the biggest contributors to relief can be how physicians relate to their patients. "When I talk to other doctors about headaches, I stress that they should show empathy with their patients and demonstrate some knowledge," Bartleson said. "I think we get frustrated when we feel like we can't cure something, so we don't want to deal with it. But sometimes just explaining things to people can be very helpful."
Neuropathic pain can be excruciating to the patient and vexing to the doctor because it is so often resistant to treatment. Neuropathy can result from diabetes, degenerative spine disease, cancer, compression and entrapment syndromes, HIV infection, herpes zoster, spinal cord injury, or stroke, or as a result of some surgeries.1,7
In 2004, Gil I. Wolfe, MD, published a review of current understanding of neuropathic pain and approaches to treating it in Muscle & Nerve.8 Wolfe is associate professor of neurology at the University of Texas Southwestern Medical Center in Dallas, where he is also the Dr Bob and Jean Smith Foundation Distinguished Chair in Neuromuscular Disease Research. "For the first time, we now have agents with a labeled indication for treating this type of pain," Wolfe said.
In his paper, he noted that the painful, or "positive," symptoms of neuropathy should be distinguished from "negative" symptoms that include numbness or reduced sensation. Positive symptoms, then, include pain that is burning, stabbing, stinging, squeezing, aching, cramping, shooting, or freezing. Add to these allodynia, whose sufferers experience pain at the slightest touch, and you have a sobering catalog of sensations that could be transposed directly from Dante's vision of Hell.
Drugs found effective for neuropathy include tricyclic antidepressants and atypical antidepressants such as bupropion, whereas selective serotonin reuptake inhibitors don't appear to work as well, Wolfe reported. Among anticonvulsants, gabapentin is a popular first-line treatment and lamotrigine(Drug information on lamotrigine) (Lamictal, GlaxoSmith- Kline) appears to have promise, whereas carbamazepine(Drug information on carbamazepine) is indicated for trigeminal neuralgia and only limited data exist for its use in neuropathy. Valproic acid seems promising, but relatively few data are available about it. Phenytoin(Drug information on phenytoin) has fallen from favor because of conflicting studies and frequent adverse events.
Other possible approaches include tramadol(Drug information on tramadol) (Ultracet, Ortho-McNeil), a nonnarcotic analgesic; opioid analgesics, which work well but typically carry with them the side effects of constipation, sedation, nausea, and addiction risk; mexiletine(Drug information on mexiletine), with mixed results so far; capsaicin, which appears to affect diabetic neuropathy but not other painful neuropathies; levodopa, which was found effective in one blind placebo-controlled study; and dextromethorphan(Drug information on dextromethorphan), a common ingredient in cough syrup that has had mixed results and is associated with frequent adverse events.8 Other researchers have reported results with new antidepressants such as duloxetine(Drug information on duloxetine) (Cymbalta, Eli Lilly) and venlafaxine (Effexor, Wyeth), as well as topical lidocaine(Drug information on lidocaine).1
Wolfe noted in the article that polypharmacy was among the most promising trends in managing neuropathic pain, and subsequent events have proved him right. "A recent paper in the New England Journal of Medicine7 supports the overall trend to use combinations of agents with different mechanisms of action," he said by phone from his Dallas office. That paper found the combination of morphine(Drug information on morphine) and gabapentin significantly more effective for neuropathic pain than either drug used alone. Moreover, the combination achieved better analgesia at lower doses of each drug than did ei- ther single agent, suggesting an additive effect that not only increases efficacy but also reduces side effects.
"There are huge opportunities in training, clinical research, and in the potential for improving patient care," according to Jack Griffin, MD, professor and chair of the Department of Neurology and chief neurologist at Johns Hopkins Hospital in Baltimore. Griffin believes that, as neurologists gain better understanding of the mechanisms of neuropathic pain, their choices of medication regimens will improve.
"For example, almost everyone's experience is that trigeminal neuralgia responds differently to medications like carbamazepine and other channel-active agents compared with painful diabetic neuropathy and postherpetic neuralgia. Not every neuropathic pain situation is the same, and not everyone will respond to the same drugs." Griffin said that newer medications with more selective action profiles will help patients but pose challenges because of increased side-effect risks.
"Patients taking infliximab(Drug information on infliximab) [Remicade, Centocor], for example, have a 10-fold increased risk of complications of disseminated tuberculosis," he said. "These very potent agents have a higher order of potential toxicity, and physicians using them will have to be very well schooled and diligent about complications."
Certain neurologic pain conditions are so rare that little is known about the most efficacious approaches to treatment. One of these is complex regional pain syndrome (CRPS), which physicians are just beginning to understand.9 According to Bartleson, CRPS often occurs after an injury in which nerves are damaged. Examples include gunshot wounds, fractures in which a nerve is impinged, and certain soft tissue injuries.
"An initial event may cause immobilization, and then you get continuing, ongoing pain," Bartleson said. "Patients can get allodynia or skin changes such as swelling or cessation of hair growth." Sometimes known as reflex sympathetic dystrophy, CRPS has been treated with varying success with opioids, tricyclic antidepressants, sodium channel blockers (including carbamazepine), and other drugs.10
Another condition of this type is post-traumatic chronic pain following a brain injury. In such patients, pain may interact with cognitive impairment, mood and anxiety disorders, and personality disorders. A combination of specialists is typically involved in patient care and rehabilitation.11
education and training
According to Argoff, these more esoteric considerations give way in daily practice to commonplace disorders such as low back pain and other musculoskeletal pain issues. Neurologists' training, he said, needs to reflect this.
"We have to provide a framework for trainees to understand not only diabetic neuropathy but the person with any type of pain syndrome," Argoff said. "Historically, more common conditions have been less interesting to neurologists, but that has to change. Let's make more sense of what's going on in the person with low back pain. Let's try to explain it scientifically so we can understand what to do clinically."
Argoff would like to see more attention paid to conditions such as fibromyalgia, soft tissue pain, painful muscle spasms, myofascial pain, and pain associated with rheumatoid arthritis and other autoimmune diseases. "We need to train people to take care of the person in their office in such a way that you do everything possible to maximize their pain relief and assess their response," he said. "What happens now in a lot of the country is, you go to a pain center and get 18 nerve blocks, and when you don't respond, they say, 'Sorry.' That's where neurologists, because they take care of people long-term, can be extremely helpful."
Peter Lars Jacobson, MD, is keenly interested in improving neurologists' training in pain management as well. Jacobson is a clinical professor in the Department of Neurology at the University of North Carolina at Chapel Hill and director of the palliative care program there. "One of the major problems has been that noncancer pain has been treated differently than cancer pain, and physician education about the management of chronic noncancer pain has been limited in the past," he said.
As Jacobson reported in a 2003 paper in Mayo Clinic Proceedings, multiple barriers still impede the treatment of chronic noncancer pain (CNP).12 These include historical concern about the subjective and objective components of CNP and its pathophysiology, lack of CNP emphasis in medical education, confusion with psychiatric disease, fear of regulatory agencies such as the Drug Enforcement Administration (DEA), a perceived hostile environment that may include other clinicians and the media, and fear of contributing to a patient's drug addiction.
Jacobson is nevertheless undaunted. "Pain is the fifth vital sign recorded in the chart, and there is no reason for someone to suffer," he said. Addressing physicians' common concern that prescribing opioids will bring the DEA to their doorstep or get them branded by colleagues as an overprescriber, Jacobson noted in the paper that the DEA's own physician's manual states: ". . . [Narcotic] drugs have a legitimate clinical use and the physician should not hesitate to prescribe, dispense, or administer them when they are indicated for legitimate medical purpose." Jacobson stated, "The main goal of the DEA is the prevention of opioid diversion, which is important; regular patient assessments and prescription monitoring by the neurologist with solid documentation should help to stop opioid diversion."
Opioid treatment is appropriate in some patients with compression fractures of vertebrae, or in those with severe peripheral neuropathy, traumatic nerve injury, brachial plexopathy or possible postsurgical problems that result in chronic pain, according to Jacobson. "These people have incredible pain, and you can change their lives," he said. When he believes such patients need opioids, Jacobson has them sign a treatment contract that includes the following safeguards for the patient and the physician:
*Only one physician authorized to prescribe controlled substances.
*Only one pharmacy named to dispense prescription.
*Refills during office hours only.
*Notification of the physician's office of any controlled substance prescriptions from another physician during emergency room treatment.
*Description of the prescription flowchart in the patient's record.
*Immediate referral to a drug treatment program or dismissal from the practice for violations of the contract.12
"If you document your examination and prescriptions correctly and examine the patients the way you should, it's not a major issue," Jacobson went on to say. "But it is very important to the patient with chronic pain. Neurologists need to learn how to manage patients with chronic pain, just as they'd manage seizures, diabetes, or any other chronic disease. To me this is what medicine is all about: treating the underlying etiology for the pain if possible, while reducing pain and suffering in patients with chronic pain in a safe and calm environment." *
1. Raja S, Haythornthwaite J. Combination therapy for neuropathic pain--which drugs, which combination, which patients? N Engl J Med. 2005; 352:1373-1375.
2. Marcus D. Tips for managing chronic pain: implementing the latest guidelines. Postgrad Med. 2003;113:49-63.
3. Centers for Disease Control and Prevention and American Diabetes Association Web sites. Available at: http://www.cdc.gov/diabetes/ statistics/incidence/fig1.htm;http://www.cdc. gov/diabetes/statistics/prev/national/ figpersons.htm; http://www.cdc.gov/diabetes/ statistics/pre/national/figpersons.htm;
http://www.diabetes.org/diabetes-statistics/ national-diabetes-factsheet.jsp. Accessed May 5, 2005.
4. American Academy of Neurology. Ethical considerations for neurologists in the management of chronic pain. Neurology. 2001;57:2166-2167.
5. Joint Commission on Accreditation of Healthcare Organizations. 2001 Hospital accreditation standards. Oakbrook Terrace, Ill: JCAHO Publications, Inc; 2001.
6. Chavin J. Cranial neuralgias and headaches associated with cranial vascular disorders. Otolaryngol Clin North Am. 2003;36:1079-1093.
7. Gilron I, Bailey JM, Tu D, et al. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352:1324-1334.
8. Wolfe G, Trivedi J. Painful peripheral neuropathy and its nonsurgical treatment. Muscle Nerve. 2004;30:3-19.
9. Stanton-Hicks M. Complex regional pain syndrome. Anesthesiol Clin North America. 2003; 21:733-744.
10. Schott GD. Reflex sympathetic dystrophy. J Neurol Neurosurg Psychiatry. 2001;71:291-295.
11. Branca B, Lake A. Psychological and neuropsychological integration in multidisciplinary pain management after TBI. J Head Trauma Rehabil. 2004;19:40-57.
12. Jacobson PL, Mann JD. Evolving role of the neurologist in the diagnosis and treatment of chronic noncancer pain. Mayo Clin Proc. 2003;78:80-84.