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Topical capsaicin therapy for neuropathic pain
Pain, 47 (1991) 247-248 Elsevier Science Publishers B.V.
247
PAIN 01878
Editorial Comment
Topical capsaicin therapy for neuropathic pain Ronald Dubner Neurobiology and Anesthesiology Branch, National Institute of Dental Research, NIH, Bethesda, MD 20892 (U.S.A.)
In this issue, Simone and Ochoa present experimental evidence for the selective action of topical capsaicin on unmyelinated peripheral nerve fibers. The findings have clinical significance because a number of clinical trials have been conducted on the effectiveness of topical capsaicin in the treatment of painful peripheral neuropathies [1,4,9]. These trials have met with limited success or have been uncontrolled. Simone and Ochoa provide evidence that repeated application of capsaicin desensitizes unmyelinated or C-fiber nociceptors, suggesting that the clinical effectiveness of capsaicin may depend on the underlying pathophysiology in each clinical condition. Evidence is accumulating that pain associated with diabetic neuropathy, postherpetic neuralgia, causalgia, reflex sympathetic dystrophy and other disorders of peripheral nerve, involves multiple etiological factors [2,5,6,8]. Such factors result in altered neuronal processing in the peripheral or central nervous system, or both. For example, it has been postulated that some painful neuropathies characterized by exaggerated responses to heat stimulation involve sensitization of C-fiber nociceptors [5]. Other studies of conditions of nerve injury suggest that ectopic nerve discharges arising from neuromas or the dorsal root ganglion contribute to the pain [3]. In addition, recent studies provide evidence that mechanical allodynia associated with causalgia-like conditions involves altered processing in the central nervous system, possibly at the level of the spinal dorsal horn [2,6,7]. The Simone and Ochoa data is useful because it gives us clues, based on possible underlying pathophysiological mechanisms, as to which types of painful neuropathy may be amenable to capsaicin treatment. In patients in which exaggerated responses to heat are present and appear to involve sensitization of C-fiber
Correspondence to: Dr. R. Dubner, Neurobiology and Anesthesiology Branch, National Institute of Dental Research, NIH, Bldg. 30, Bethesda, MD 20892, U.S.A.
nociceptors, capsaicin may be particularly effective since repeated topical application desensitizes the Cfiber nociceptors. In contrast, painful conditions in which abnormal discharges arise from damaged nerves that are not connected to their peripheral receptors are unlikely to be affected by capsaicin. This can be determined by clinical examination, including the determination of threshold and suprathreshold responses to thermal and mechanical stimulation and the judicious use of local anesthetics. Finally, we need to consider those conditions of mechanical allodynia in which altered processing in the central nervous system appears to be important. These patients exhibit mechanical allodynia that extends outside the injured dermatome and that can be eliminated or reduced by peripheral nerve ischemic or local anesthetic blocks [2,7]. The effectiveness of capsaicin in these conditions may depend on the source of the peripheral input that maintains the altered CNS processing. If the origin of the peripheral drive is from intact, either normal or sensitized, C-fiber nociceptors located near the site of nerve injury, then capsaicin should be effective. On the other hand, if the peripheral drive involves intact myelinated afferents, then capsaicin treatment may not be useful. Recent evidence suggests that C-fiber nociceptor drive may maintain the mechanical allodynia in some cases of causalgic-like pains [7]. The diagnosis can be helped by thorough sensory examination, particularly near the site of injury, and the use of local anesthetic injections. The lack of consistent results following capsaicin treatment for painful neuropathies is likely due to the heterogeneity of the underlying neuronal mechanisms that account for the pain. Only a subset of patients may derive any therapeutic advantage because of the multiple mechanisms at play. For similar reasons, the effectiveness of various pharmacological agents in the treatment of neuropathic pain may meet with limited success. We need to continue to improve our understanding of the pathophysiology of neuropathic pain so
248
that diagnostic and treatment approaches can be targeted for subsets of conditions with similar etiologies and mechanisms of action.
5
References
6
1 Bernstein, J.E., Bickers, D.R., Dahl, M.V. and Roshal, J.Y., Treatmerit of chronic postherpetic neuralgia with topical capsaicin, J. Am. Acad. Derm., 17 (1987) 93-96. 2 Campbell, J.N., Raja, S.N. and Meyer, R.A., Painful sequelae of nerve injury. In: R. Dubner, G.F. Gebhart and M.R. Bond (Eds.), Proc. of the Vth World Congress on Pain, Elsevier, Amsterdam, 1988, pp. 135-143. 3 Chabal, C., Jacobson, U, Russell, L.C. and Burchiel, K.J., Pain response to perineuromal injection of normal saline, gallamine and lidocaine in humans, Pain, 36 (1989) 321-325. 4 Chad, D.A., Aronin, N., Lundstrom, R., McKeon, P., Ross, D.,
7
8
9
Molitch, M., Schipper, H.M., Stall, G., Dyess, E. and larsy, I)., l)oes capsaicin relieve the pain of diabetic neuropathy? Pain, 42 (199{1) 387-388. ( line, M.A., Ochoa, J. and Torebj6rk, H.E., Chronic hyperalgesia and skin warming caused by sensitized C nociceptors, Brain. 112 (1989) 621-647. Dubner, R., Neuronal plasticity and pain following peripheral tissue inflammation or nerve injury, In: M.R. Bond, J.E. Charlton and C.J. Woolf (Eds.), Proc. of the VIth World Congress on Pain. Elsevier, Amsterdam, 1991, pp. 263-276. Lynch, S., Gracely, R.H. and Bennett, G.J., Ongoing input from a putative focus of nociccptor discharge maintains the abnormal pain sensations of reflex sympathetic dystrophy, Soc. Neurosci. Abst., 16 (19901 1143. Price, D.D., Bennett. G.J. and Rafii, A., Psychological observations on patients with neuropathic pain relieved by a sympathetic block, Pain, 36 (19891 273-288. Watson, C.P.N., Evans, R.J. and Watt, V.R., Post-herpetic neuralgia and topical capsaicin, Pain, 33 (19881 333-340.
247
PAIN 01878
Editorial Comment
Topical capsaicin therapy for neuropathic pain Ronald Dubner Neurobiology and Anesthesiology Branch, National Institute of Dental Research, NIH, Bethesda, MD 20892 (U.S.A.)
In this issue, Simone and Ochoa present experimental evidence for the selective action of topical capsaicin on unmyelinated peripheral nerve fibers. The findings have clinical significance because a number of clinical trials have been conducted on the effectiveness of topical capsaicin in the treatment of painful peripheral neuropathies [1,4,9]. These trials have met with limited success or have been uncontrolled. Simone and Ochoa provide evidence that repeated application of capsaicin desensitizes unmyelinated or C-fiber nociceptors, suggesting that the clinical effectiveness of capsaicin may depend on the underlying pathophysiology in each clinical condition. Evidence is accumulating that pain associated with diabetic neuropathy, postherpetic neuralgia, causalgia, reflex sympathetic dystrophy and other disorders of peripheral nerve, involves multiple etiological factors [2,5,6,8]. Such factors result in altered neuronal processing in the peripheral or central nervous system, or both. For example, it has been postulated that some painful neuropathies characterized by exaggerated responses to heat stimulation involve sensitization of C-fiber nociceptors [5]. Other studies of conditions of nerve injury suggest that ectopic nerve discharges arising from neuromas or the dorsal root ganglion contribute to the pain [3]. In addition, recent studies provide evidence that mechanical allodynia associated with causalgia-like conditions involves altered processing in the central nervous system, possibly at the level of the spinal dorsal horn [2,6,7]. The Simone and Ochoa data is useful because it gives us clues, based on possible underlying pathophysiological mechanisms, as to which types of painful neuropathy may be amenable to capsaicin treatment. In patients in which exaggerated responses to heat are present and appear to involve sensitization of C-fiber
Correspondence to: Dr. R. Dubner, Neurobiology and Anesthesiology Branch, National Institute of Dental Research, NIH, Bldg. 30, Bethesda, MD 20892, U.S.A.
nociceptors, capsaicin may be particularly effective since repeated topical application desensitizes the Cfiber nociceptors. In contrast, painful conditions in which abnormal discharges arise from damaged nerves that are not connected to their peripheral receptors are unlikely to be affected by capsaicin. This can be determined by clinical examination, including the determination of threshold and suprathreshold responses to thermal and mechanical stimulation and the judicious use of local anesthetics. Finally, we need to consider those conditions of mechanical allodynia in which altered processing in the central nervous system appears to be important. These patients exhibit mechanical allodynia that extends outside the injured dermatome and that can be eliminated or reduced by peripheral nerve ischemic or local anesthetic blocks [2,7]. The effectiveness of capsaicin in these conditions may depend on the source of the peripheral input that maintains the altered CNS processing. If the origin of the peripheral drive is from intact, either normal or sensitized, C-fiber nociceptors located near the site of nerve injury, then capsaicin should be effective. On the other hand, if the peripheral drive involves intact myelinated afferents, then capsaicin treatment may not be useful. Recent evidence suggests that C-fiber nociceptor drive may maintain the mechanical allodynia in some cases of causalgic-like pains [7]. The diagnosis can be helped by thorough sensory examination, particularly near the site of injury, and the use of local anesthetic injections. The lack of consistent results following capsaicin treatment for painful neuropathies is likely due to the heterogeneity of the underlying neuronal mechanisms that account for the pain. Only a subset of patients may derive any therapeutic advantage because of the multiple mechanisms at play. For similar reasons, the effectiveness of various pharmacological agents in the treatment of neuropathic pain may meet with limited success. We need to continue to improve our understanding of the pathophysiology of neuropathic pain so
248
that diagnostic and treatment approaches can be targeted for subsets of conditions with similar etiologies and mechanisms of action.
5
References
6
1 Bernstein, J.E., Bickers, D.R., Dahl, M.V. and Roshal, J.Y., Treatmerit of chronic postherpetic neuralgia with topical capsaicin, J. Am. Acad. Derm., 17 (1987) 93-96. 2 Campbell, J.N., Raja, S.N. and Meyer, R.A., Painful sequelae of nerve injury. In: R. Dubner, G.F. Gebhart and M.R. Bond (Eds.), Proc. of the Vth World Congress on Pain, Elsevier, Amsterdam, 1988, pp. 135-143. 3 Chabal, C., Jacobson, U, Russell, L.C. and Burchiel, K.J., Pain response to perineuromal injection of normal saline, gallamine and lidocaine in humans, Pain, 36 (1989) 321-325. 4 Chad, D.A., Aronin, N., Lundstrom, R., McKeon, P., Ross, D.,
7
8
9
Molitch, M., Schipper, H.M., Stall, G., Dyess, E. and larsy, I)., l)oes capsaicin relieve the pain of diabetic neuropathy? Pain, 42 (199{1) 387-388. ( line, M.A., Ochoa, J. and Torebj6rk, H.E., Chronic hyperalgesia and skin warming caused by sensitized C nociceptors, Brain. 112 (1989) 621-647. Dubner, R., Neuronal plasticity and pain following peripheral tissue inflammation or nerve injury, In: M.R. Bond, J.E. Charlton and C.J. Woolf (Eds.), Proc. of the VIth World Congress on Pain. Elsevier, Amsterdam, 1991, pp. 263-276. Lynch, S., Gracely, R.H. and Bennett, G.J., Ongoing input from a putative focus of nociccptor discharge maintains the abnormal pain sensations of reflex sympathetic dystrophy, Soc. Neurosci. Abst., 16 (19901 1143. Price, D.D., Bennett. G.J. and Rafii, A., Psychological observations on patients with neuropathic pain relieved by a sympathetic block, Pain, 36 (19891 273-288. Watson, C.P.N., Evans, R.J. and Watt, V.R., Post-herpetic neuralgia and topical capsaicin, Pain, 33 (19881 333-340.