Cancer Pain: What's a Neurologist's Role?

Managing cancer pain and end-of-life care has traditionally been the bailiwick of oncologists, nurses, and anesthesiologists. Except for rare instances, neurologists have not been leaders in the field, which makes Kathleen Foley, MD, one of a kind. Active in the death-and-dying movement for the past 30 years, she was the first neurologist to start a cancer pain management fellowship program that initially took only neurologists.

Foley started the program at Memorial Sloan-Kettering Cancer Center in 1981. In the 1980s and 1990s, many neurologists trained with her. Memorial's program took only a few fellows each year, making it hard for neurologists to build a critical mass.

Turf wars have complicated the rocky road that neurologists have traveled to get into the field. Russell K. Portenoy, MD, described it this way: "We were at the mercy of oncologists and a panel of pain specialists who were either procedure-oriented or intervention-oriented." Portenoy, chair of the American Board of Hospice and Palliative Medicine and chair of the Department of Pain Medicine and Palliative Care at Beth Israel Medical Center in New York, has been one of the most avid proponents of neurologists' participation in hospice and palliative care medicine. Palliative care medicine is more encompassing than pain management and includes treatment of patients who have such conditions as fatigue, sleep disorders, and anorexia. Portenoy stressed the following, however: "Pain [management] has got to be part of palliative medicine. Without incorporating it, you are giving people a crumb when they should get a loaf."

Traditionally, medical school training and neurology residency programs have given little attention to the management of malignant pain. Accordingly, when it comes to selecting a specialty, neurologists have had few role models to inspire them to choose a career in cancer pain practice and palliative care.

John T. Farrar, MD, assistant professor of neurology and chair of the Cancer Center's Pain Management Program Committee at the University of Pennsylvania, described why neurologists are few and far between in this field of medicine. "There are only a few neurologists who have been interested in treating [patients who have] chronic pain other than headache. To help with the diagnosis, neurologists will see patients with pain that may have a nervous system origin," he said, "but few are interested in treating such patients over the long term and even fewer are involved in pain clinics." Pain clinics are staffed primarily by anesthesiologists, although other specialists sometimes participate, he explained.

Misha Backonja, MD, professor of neurology and director of the University of Wisconsin-Madison Pain Clinic, amplified Farrar's remarks: "By and large, neurologists have had no training in interventional procedures. 'Diagnose and adios' has been a mantra for neurologists," he said. "Moreover, neurologists tend to be 'opio-phobes.'"

But Neil Slatkin, MD, argued that the neurologist's unique skills in diagnosing pain syndromes and taking exhaustive patient histories makes him or her a specialist at evaluating and treating both nonmalignant and malignant pain. "We are known as one of the medical specialties that is obsessively comprehensive in taking a medical history," said Slatkin, director of the Department of Supportive Care and Palliative Medicine at City of Hope National Medical Center in Duarte, CA. "It would be a major mistake for doctors to assume that all symptoms reported by patients with cancer stemmed from the cancer itself."

As an example, Slatkin described a patient who had reported severe pain. "It turned out that the pain had nothing to do with the cancer. The primary problem was Parkinson's disease, which other doctors would have missed." Slatkin said that with appropriate treatment, the patient was able to be weaned from all narcotics and that the Parkinson disease was effectively managed.

Neurologists have special expertise in cognitive assessments, including evaluation of the patient's recall of pain relief. A thorough neurologic examination can isolate such pain syndromes as spasticity, myoclonus, epileptic seizures, and akathisia. In addition to performing initial physical examinations and first-line cognitive dysfunction tests, neurologists also play an important role in referring patients who have cognitive deficits to neuropsychologists.

PHARMACOLOGIC TREATMENTS

Until recently, intense cancer pain was considered unmanageable, but in about 70% of patients with cancer, it can be controlled by using simplified opioid regimens.^1-3 Prescribing must be individualized, said Sharon Weinstein, MD, director of Huntsman Cancer Institute's Pain Medicine and Palliative Care Program in Salt Lake City. "It really depends on patient convenience, mental status, and how many pills people are taking. There are a lot of psychological factors. If a patient has to take 15 to 20 drugs on schedule, [a] once-a-day [regimen] might be easier to tolerate." She stressed that there is no optimal way to prescribe pain medication, but she acknowledged that when patients are taking many medications each day, the risk of errors increases.

Neurologists bring special expertise to cancer pain management, however. Their familiarity with drugs that are used to treat nonmalignant neuropathic pain is an asset. Furthermore, drug conversion charts are easy to learn and their use helps maximize pain control, according to Farrar, Portenoy, and others who spoke with Applied Neurology for this article.

Opioids are the mainstay of treatment and are sometimes used in combination with NSAIDs. Extended- release formulations of oxycodone and other opioids are now available, but their use is controversial.^4,5

If a patient has pain 24 hours a day, 7 days a week, he or she needs pain relief that is effective for that amount of time, said Backonja. "Especially with short-acting opioids, there is a huge issue of patients focusing on drug-taking [because of the] short-acting duration of the medications, rather than concentrating on obtaining skills [for] managing pain," he said. "In addition, there is probably a ton of biologic reasons why short-acting opioids have adverse effects on chronic pain, such as development of tolerance [or] multiple episodes of withdrawal."

The cyclooxygenase (COX)-2 inhibitors, used alone or in combination with opioids, have an excellent track record in palliative care.^6-8 Some health care professionals considered the withdrawal of rofecoxib (Vioxx, Merck) a loss for palliative care medicine. "The withdrawal of Vioxx was one of the darkest days of my professional career. Why couldn't Merck have put a black-box warning on it?" Slatkin lamented. Concerns that the COX-2 inhibitors would lower platelet count were not justified, explained Farrar. Although he realized that Merck had no choice, he questioned whether an exception could have been made for the treatment of pain in patients with terminal illness.

Anticonvulsants, particularly gabapentin (Neurontin, Pfizer), have been used as first-line coanalgesics; research has shown gabapentin to be effective in the management of neuropathic cancer pain.^9-11 Many pain specialists have said that they consider gabapentin a first-line treatment because of its long track record in treating nonmalignant neuropathic pain.

Because depression, anxiety, and sleep disturbances occur in patients with cancer, the prescription of antidepressants, benzodiazepines, and anxiolytics is common. However, these drug classes have been understudied in the context of cancer.

Ziconotide (Prialt, Elan Pharmaceuticals), a snail toxin that was approved by the FDA in March, is delivered to the spine with an intrathecal catheter and pump. Patient selection criteria are critical for this treatment, according to John Loesser, MD, professor of neurologic surgery and anesthesiology at the University of Washington, Seattle. It is best used in patients who have pain that is refractory to opioid therapy or in those with intolerable opioid-related side effects, according to Loesser.

"The patients that I see who are candidates for the pump account for a tiny fraction of the patients in need of pain relief," he said. Although an important benefit of the pump is its delivery system, which allows patients to be ambulatory, it has important risks, such as infection. Loesser said that using a single agent could lower risk, but many physicians use multiple agents. Use of intrathecal delivery systems is recommended only for well-trained, experienced physicians.

Eduardo Bruera, MD, and colleagues have been investigating the efficacy of psychostimulants for fatigue associated with the cancer and its treatments.¹² Bruera is chair of the International Association for Hospice and Palliative Care and of the Department of Palliative Care and Rehabilitation Medicine at the University of Texas M.D. Anderson Cancer Center, where he also is clinical medical director and chief operating officer of the Palliative Care and Rehabilitation Medicine Center. According to Bruera and his team, fatigue can be so severe that some patients prefer to stop therapy. Stimulants tend to be used to counteract the sedating effects of opioids and the fatigue associated with cancer.

Intriguing research on cytokine-based neuroim-munologic mechanisms is currently under way.^13,14 Charles S. Cleeland, PhD, director of the Pain Research Group at the University of Texas M. D. Anderson Cancer Center, has led the research in this area. Cytokines are being studied not only as potential drug targets for modulation of cancer pain but also as targets for amelioration of cancer-related symptoms, including pain, fatigue, sleep disturbance, cognitive dysfunction, and affective symptoms.

"Progress in understanding the mechanisms that underlie these symptoms may lead to new therapies for symptom control. Recently, some of these symptoms have been related to the actions of certain cytokines that produce a constellation of symptoms and behavioral signs when given exogenously to both humans and animals. The cytokine-induced sickness behavior that occurs in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines has much in common with the symptoms experienced by cancer patients," the researchers wrote in a report published in Neuroimmunomodulation in 2004. Cleeland said that he sees a lot of potential in this area of research, but "getting the drug companies interested in it will remain a problem until they see its market potential."

Cannabinoid research also shows promise, according to many health care professionals.^15,16 The data consist largely of animal studies and are still considered investigational.

A PUBLIC HEALTH PROBLEM

Pain and palliative care is one area that is likely to grow exponentially both in clinical practice and in basic science. Many national panels, including those responsible for the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT),¹⁷ the Institute of Medicine's Report on Improving Palliative Care,¹⁸ and the 2002 NIH State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression and Fatigue,¹⁹ have exerted pressure on the NIH and health insurers to make pain management and palliative care high public health priorities. Medical school education, residency training, fellowship programs, and continuing medical education have incorporated more material on pain into curricula. "The [Accreditation Council for Graduate Medical Education] Boards have changed some of the questions so that more relate to pain," said Weinstein.

In May, the American Board of Internal Medicine and American Board of Family Practice agreed to cosponsor subspecialty certification in hospice and palliative medicine.^20,21 In a July 6 memo to members of the American Academy of Neurology's Pain and Palliative Care Section, Portenoy strongly urged practicing neurologists to make their voices heard by the American Board of Psychiatry and Neurology, demonstrating their interest in a neurology subspecialty. "This viewpoint needs to be heard by the Board now, during the next 4- to 6-month window," he wrote. (See also www.aahpm.org/about/campaign letter.doc.)

With the granting of subspecialty accreditation, neurologists will have an opportunity to attain leadership positions. Many jobs in pain management and palliative care remain unfilled at present. According to Portenoy, subspecialty status in neurology "would encourage the development of palliative care within neurology. Because many neurologists are involved in a wide range of neurodegenerative conditions, [neurology] should be home to the discipline." *

Additional Resources on Pain Management

• The American Pain Society (APS) and National Comprehensive Cancer Network (NCCN) published new evidence-based guidelines for cancer pain practice in 2005. The guideline panels were consensus-driven, with some overlap of participants. Recommendations are ranked by the strength of the evidence. The APS guidelines are available at www.ampainsoc.org/pub/cancer.htm. The NCCN guidelines are available at www.nccn.org/professionals/ physician_gls/default.asp.

• The Pain and Policy Studies Group at the University of Wisconsin Comprehensive Cancer Center is an excellent source for news and research (www.medsch.wisc.edu/ painpolicy). A World Health Organization Collaborating Center for Policy and Communications in Cancer Care, it addresses both domestic and international policy issues.

• The American Board of Psychiatry and Neurology of- fers subspecialty certificates in pain management. Information is available at www.abpn.com/certification/ painmanagement.html.

Timeline: Neurologists and Cancer Pain and Palliative Care

1981

First neurology-based cancer pain fellowship program opens at Memorial Sloan-Kettering Cancer Center (MSKCC). 1980s-Present

The small numbers of neurology fellows initially trained at MSKCC start clinical pain and palliative care practices or basic science research programs throughout the country.

1995

The American Academy of Neurology's Pain Section defines model curriculum for neurology-based pain education. 1990s-Present

Programs become increasingly interdisciplinary and set standards for training requirements and faculty in oncology, neurology, rehabilitation, and psychiatry. Neurologists are more actively involved.

2000

ACGME identifies program requirements for neurology pain management subspecialty fellowships. The curriculum is based on certification requirements set by the American Board of Psychiatry and Neurology.

2003

The Project on Death in America and the Emily Davie and Joseph S. Kornfeld Foundation award 2-year grants to 7 institutions to help build capacity of pain fellowship programs and establish palliative medicine as a recognized subspecialty. 2005

Leaders in the pain and palliative care community press for hospice and palliative care subspecialty accreditation and seek support from the American Academy of Neurology.

2005

The American Board of Internal Medicine and American Board of Family Medicine agree to cosponsor the subspecialty.

ACGME, Accreditation Council for Graduate Medical Education.

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