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加拿大物理治疗和康复学会年会
Treatment Modalities for Neuropathic Pain and Spasticity From the CAPM and R Annual Meeting: A Canadian Thought-Leader Perspective From John Bowering, MD
2005年6月15－18日
加拿大安大略省渥太华
June 15-18, 2005; Ottawa, Ontario, Canada
John B. Bowering, MD
Introduction
The Canadian Association of Physical Medicine & Rehabilitation (CAPM&R) Annual Meeting was held recently in Ottawa, Ontario. A variety of studies were presented that focused on quality-of-life issues as well as newer treatment modalities for neuropathic pain and spasticity associated with several common neurodegenerative diseases.
Neuropathic pain results from a primary lesion or dysfunction in the nervous system, which can result from both central and peripheral mechanisms. These mechanisms are not completely understood and can generate a variety of symptoms, including dysesthesia, hyperalgesia, and allodynia, as well as symptoms of autonomic dysfunction presenting in the form of vasomotor and sudomotor changes.
Neuropathic pain can be associated with a number of disease states, including multiple sclerosis, postherpetic and trigeminal neuralgia, diabetes, stroke, and spinal cord injury (SCI). There are also a variety of associated postsurgical neuropathic pain syndromes, including postthoracotomy pain, phantom limb pain following amputation, postmastectomy, postaxillary lymph node dissection, and pain following radical neck dissection.[1]
Optimal management of neuropathic pain continues to present a major challenge to clinicians. It requires an interdisciplinary approach with collaboration between psychologists, physical and occupational therapists, and physicians with a special interest in pain medicine.[2] A variety of pharmacologic agents have been used to assist with management, including antidepressants, anticonvulsants, opioids, topical agents, local anesthetics, alpha-2 agonists, NMDA antagonists, and corticosteroids.[1] In addition, neuraxial catheters, as well as spinal cord and/or deep brain stimulation, have been employed.
It is well known that pain can be associated with a variety of psychological disturbances, including anxiety, depression, frustration, and anger, and may also significantly impair one's coping skills.
A very important issue in many patients with neuropathic pain is the disturbance of normal sleep. In general, increasing pain severity results in more significant sleep disturbances, thereby producing daytime fatigue and restricting daily activities. This in turn may exacerbate anxiety and/or depression.
At the CAPM&R meeting, Dr. Arneja[3] presented a prospective study examining the temporal relationship between limb amputation and sleep disturbance. Patients were divided into 3 groups based on the time between the date of their amputation and the date of their interview, ie, group 1 (1-2 months), group 2 (3-8 months), and group 3 (9-15 months). Dr. Arneja found that there was a significant reduction in the frequency of sleep disturbance in Groups 2 and 3, while the prevalence of stump and phantom limb pain did not change significantly.
Obstructive sleep apnea (OSA) is known to have a significant impact on individual morbidity and mortality. Dr. Leduc[4] presented data estimating the prevalence of OSA in patients with a cervical cord injury and identified risk factors for its development. Adults with no prior history of OSA who suffered complete or incomplete cervical cord injury of greater than 6 months' duration were enrolled. All patients were given standard overnight polysomnography, and diagnostic criteria generated by the American Academy of Sleep Medicine were used. Fifty-five percent of the patients were diagnosed with OSA. In this group, 36% met the criteria for having severe OSA. Daytime sleepiness, body mass index, and neck circumference were identified as associated risk factors.
A patient's quality of life may also be affected by a delay in return to work following an injury, which can have a significant impact on the patient's self-esteem. Dr. Hebert[5] conducted a retrospective analysis of the Alberta Workers Compensation Board's database from 1995 to 2000 examining factors predictive of return to work and days of total disability in persons requiring a lower-extremity amputation resulting from a work-related injury. Surgical procedures ranged from toe amputations to above-knee amputations. In this study, 58% of the individuals returned to work; factors predictive of return to work included lower-level amputations and higher gross annual income. The study authors also noted that amputations at the level of the toe still resulted in a mean of 127 days of total disability.
Dr. Wiebe[6] conducted a retrospective cohort study to determine which factors were prognostic in predicting return to work following lumbar spine surgery in a compensation population. Four factors significantly predicted a poorer outcome in returning to work: (1) age older than 50 years; (2) duration of employment less than 2 years with the employer with which the injury was sustained; (3) more extensive surgery; (4) and the presence of red flags in the patient's history.
A variety of presentations at the CAPM&R meeting focused on new treatment strategies for neuropathic pain in specific disease states.
In clinical practice, cannabinoids have been used mainly as antiemetics in cancer patients receiving chemotherapy. More recently, cannabinoids have received attention for their use as analgesics for certain chronic pain conditions.
Dr. Young[7] presented results from a randomized controlled trial of delta-9 tetrahydrocannabinol and cannabidiol administered as an oromucosal spray in patients with multiple sclerosis suffering from neuropathic pain. Sixty-six patients were enrolled in this study. Delta-9 tetrahydrocannabinol/cannabidiol or placebo spray was administered over a 4-week treatment period. Patients who received delta-9 tetrahydrocannabinol/cannabidiol experienced a significant reduction in neuropathic pain as well as a significant improvement in sleep disturbance, both based on an 11-point pain numerical rating scale. Dr. Young also concluded that the drug was well tolerated by patients.
Using a rat model for inducing global ischemia, Dr. Yang[8] examined the effects of the cannabinoid HU210 on neuronal regeneration following a stroke. The first 2 groups of rats received ischemia and the third group received sham operation without ischemia. On days 4 and 5 post operation, all rats received intraperitoneal injections of BrdU (50 mg/kg) to label the newborn neural cells. Two hours later, twice-daily intraperitoneal injections of HU210 (100 micrograms/kg) were started in group 1, and twice-daily intraperitoneal injections of vehicle were started in groups 2 and 3. These injections were continued for 2 weeks. Chronic treatment with this cannabinoid resulted in a significant increase in newborn neurons in group 1 compared with the 2 groups that did not receive HU210. Dr. Yang concluded that this may represent a novel therapeutic strategy for managing neuronal loss in the poststroke patient.
Methadone is a synthetic opioid with significant analgesic properties. It has been used in the management of both cancer and neuropathic pain, and represents an appropriate alternative when pain remains poorly controlled or when side effects limit dosing of other opioids.
Dr. Koshi[9] presented a case series of 3 patients with spinal cord injuries. Each patient experienced neuropathic pain and was started on methadone after treatment failure with a variety of other pain medications. The effectiveness of methadone was measured using a 10-point pain scale. After the dose of methadone had been stabilized, Dr. Koshi noted a decrease in the mean average, mean maximal, and mean minimal pain intensity with little impairment from side effects.
Individuals who suffer from an incomplete SCI may experience significant difficulties with gait and ambulation due to muscle spasticity. Dr. Short[10] evaluated the effect of botulinum toxin (BTX-A) on ambulation in 4 patients who presented with spastic gait and SCI. BTX-A was administered to one or both of the lower extremities of each patient with the ambulation profile measured before and after treatment. All individuals showed improvement in a variety of ambulation parameters, including independent walking in 2 patients who had required assistance before therapy.
Dr. Graboski[11] presented a double-blind, randomized, crossover trial comparing trigger-point injections with BTX-A or 0.5% bupivacaine in 18 patients with myofascial pain syndrome. Subjects were randomly assigned to receive initial injections of either pharmacologic agent. Following trigger-point injection and a "2 week wash-out period," all patients received the other agent at the same trigger points. Magnitude and duration of pain relief, effect on functional ability, and satisfaction were measured. No significant difference was observed between agents.
Neuropathic pain, which was once considered a distinct entity associated with certain disease states, is now considered to be an integral part of chronic pain syndromes. It is associated with significant morbidity and in many instances has a detrimental impact on quality of life. As we gain a clearer understanding of the underlying mechanisms that play a role in neuropathic pain, we hope to be able to target them with new pharmacologic therapies such as those discussed here.