Early and late effects of prolonged topical capsaicin on cutaneous sensibility and neurogenic vasodilatation in humans

&NA; Cutaneous sensibility and neurogenic vasodilatation (flare) were measured before, during and after long‐term topical application of capsaicin in humans. Each subject applied a vehicle cream containing 0.075% capsaicin (Axsain, GalenPharma Inc.) to a 4 cm2 area of skin on one volar forearm and vehicle alone to an identical treatment area on the other forearm, according to a double‐blind procedure. Each substances was applied 4 times/day for 6 weeks. Psychophysical measurements of sensory detection thresholds, magnitude of suprathreshold heat pain, magnitude and duration of histamine‐induced itch and flare area were obtained before, at 1, 3 and 7 days after the first application, and once a week thereafter for a total of 8 weeks. Capsaicin produced mild burning in all subjects which diminished in magnitude and duration over several weeks. Capsaicin significantly altered detection thresholds for heat pain and the magnitude of pain produced by suprathreshold painful stimuli. Mean detection threshold for heat pain was lowered 1.6°C following 1 day of capsaicin application but subsequently increased to become elevated 3.5°C after 6 weeks of application. In addition, mean magnitude of suprathreshold heat pain diminished progressively after 1 week. Heat pain thresholds returned to or near pretreatment values within 2 weeks after discontinuing application. Detection thresholds for touch, cold sensation and pain induced by low temperature and by mechanical stimulation were not altered by capsaicin. Similarly, capsaicin did not alter the magnitude or duration of itch produced by intradermal injection of 1 &mgr;g histamine. However, the area of flare produced by histamine was significantly reduced in capsaicin‐treated skin. These studies demonstrate that prolonged application of capsaicin at low concentration selectively diminishes sensations of heat pain and neurogenic vasodilatation, presumably via desensitization of heat‐sensitive nociceptors. It is also shown that the decrease in heat pain is temporary and is maintained with repeated capsaicin application. There appears to be a therapeutic role for capsaicin in cutaneous painful syndromes mediated, at least in part, by activity of heat‐sensitive nociceptors.

[1]  C Peter N Watson,et al.  Post-herpetic neuralgia and topical capsaicin , 1988, Pain.

[2]  R. Tuckett,et al.  Response to an itch-producing substance in cat. I. Cutaneous receptor populations with myelinated axons , 1987, Brain Research.

[3]  Robert H. LaMotte,et al.  Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin , 1989, Pain.

[4]  R. LaMotte,et al.  Hypothesis for novel classes of chemoreceptors mediating chemogenic pain and itch , 1987, PAIN.

[5]  G. H. Bishop,et al.  Evidence for a double peripheral pathway for pain. , 1958, Science.

[6]  J. Ochoa,et al.  Heat and mechanical hyperalgesia induced by capsaicin. Cross modality threshold modulation in human C nociceptors. , 1989, Brain : a journal of neurology.

[7]  H. Wolff,et al.  STUDIES ON PAIN. A NEW METHOD FOR MEASURING PAIN THRESHOLD: OBSERVATIONS ON SPATIAL SUMMATION OF PAIN , 1940, The Journal of clinical investigation.

[8]  J. Szolcsányi,et al.  A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain. , 1977, Journal de physiologie.

[9]  J. Szolcsányi Selective responsiveness of polymodal nociceptors of the rabbit ear to capsaicin, bradykinin and ultra‐violet irradiation. , 1987, The Journal of physiology.

[10]  Robert H. LaMotte,et al.  Response properties of high-threshold cutaneous cold receptors in the primate , 1982, Brain Research.

[11]  P. Wall,et al.  Effects of capsaicin applied locally to adult peripheral nerve. I. Physiology of peripheral nerve and spinal cord , 1981, PAIN®.

[12]  K. Hagbarth,et al.  Ectopic sensory discharges and paresthesiae in patients with disorders of peripheral nerves, dorsal roots and dorsal columns , 1984, Pain.

[13]  R. LaMotte,et al.  Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms. , 1991, Journal of neurophysiology.

[14]  E. Torebjörk,et al.  Central suppression of cold-induced C fibre pain by myelinated fibre input , 1989, Pain.

[15]  R. W. Foster,et al.  The action of some chemical irritants on somatosensory receptors of the cat , 1981, Neuropharmacology.

[16]  D. Bickers,et al.  Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study. , 1987, Journal of the American Academy of Dermatology.

[17]  J. Ochoa,et al.  Release of cold-induced burning pain by block of cold-specific afferent input. , 1990, Brain : a journal of neurology.

[18]  H. E. Torebjörk,et al.  Afferent C units responding to mechanical, thermal and chemical stimuli in human non-glabrous skin. , 1974, Acta physiologica Scandinavica.

[19]  P. Kenins Responses of single nerve fibres to capsaicin applied to the skin , 1982, Neuroscience Letters.

[20]  B. Lynn Capsaicin: actions on nociceptive C-fibres and therapeutic potential , 1990, Pain.

[21]  A. Jancsó-Gábor,et al.  Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones , 1977, Nature.

[22]  H. Fruhstorfer,et al.  Sensibility Abnormalities in Neuralgic Patients Studied by Thermal and Tactile Pulse Stimulation , 1984 .

[23]  B. Lynn,et al.  VASCULAR AND SENSORY RESPONSES OF HUMAN SKIN TO MILD INJURY AFTER TOPICAL TREATMENT WITH CAPSAICIN , 1981, British journal of pharmacology.

[24]  R. LaMotte,et al.  Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia. , 1991, Journal of neurophysiology.

[25]  H. Fruhstorfer,et al.  Method for quantitative estimation of thermal thresholds in patients. , 1976, Journal of neurology, neurosurgery, and psychiatry.

[26]  R. LaMotte,et al.  The magnitude and duration of itch produced by intracutaneous injections of histamine. , 1987, Somatosensory research.

[27]  J. Ochoa,et al.  Sensations evoked by intraneural microstimulation of C nociceptor fibres in human skin nerves. , 1989, The Journal of physiology.

[28]  H. E. Torebjörk,et al.  Chronic hyperalgesia and skin warming caused by sensitized C nociceptors. , 1989, Brain : a journal of neurology.

[29]  M. H. Jones Evidence for a Double Peripheral Pathway for Pain. , 1958, Science.

[30]  H. Handwerker,et al.  Selective excitation by capsaicin of mechano-heat sensitive nociceptors in rat skin , 1988, Brain Research.

[31]  Robert H. LaMotte,et al.  Hyperalgesia to heat after intradermal injection of capsaicin , 1987, Brain Research.

[32]  D. Kenshalo,et al.  Spatial summation on the forehead, forearm, and back produced by radiant and conducted heat. , 1967, Journal of comparative and physiological psychology.

[33]  Lawrence E. Marks,et al.  Spatial summation and the dynamics of warmth sensation , 1971 .

[34]  K. Hagbarth,et al.  Microelectrode recordings from transected nerves in amputees with phantom limb pain , 1981, Neuroscience Letters.

[35]  R. Tuckett,et al.  Response to an itch-producing substance in cat. II. Cutaneous receptor populations with unmyelinated axons , 1987, Brain Research.

[36]  M. Letinsky,et al.  A preparation for studying dystrophic avian muscle and neuromuscular junctions , 1982, Muscle & nerve.

[37]  Maria Fitzgerald,et al.  Capsaicin and sensory neurones — a review , 1983, Pain.

[38]  H. Hensel,et al.  The effect of capsaicin on the response characteristic of human C-polymodal nociceptors , 1983 .

[39]  H. Handwerker,et al.  The effect of capsaicin application to a peripheral nerve on impulse conduction in functionally identified afferent nerve fibres , 1983, Brain Research.

[40]  J. Mchaffie,et al.  Spatial summation of heat-induced pain: influence of stimulus area and spatial separation of stimuli on perceived pain sensation intensity and unpleasantness. , 1989, Journal of neurophysiology.

[41]  H. Wolff,et al.  Pain Sensations and Reactions , 1953, Neurology.

[42]  H. E. Torebjörk,et al.  Abnormal spontaneous activity in single sensory nerve fibers in humans. , 1982, Muscle & nerve.