Capsaicin: Actions on C Fibre Afferents That May Be Involved in Itch
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Capsaicin selectively excites C-polymodal nociceptors in mammalian skin. In the rat, the only species so far studied in detail, a long-term desensitization of a subpopulation of C-polymodal nociceptors occurs after the initial excitation. After nerve treatment, permanent loss of some C-polymodal nociceptors is found in the rat. It is argued that capsaicin must act primarily on C fibres involved in signalling about pain and not itch, although there may be overlap between the C afferents involved in these two nociceptive sensations. The possibility is raised that C mechanoreceptors, with their good histamine sensitivity, are also involved in itch.Keywords:
Capsaicin
Nociceptor
Mechanoreceptor
Pain is "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". The processing of sensory signals evoked by noxious stimuli that injure or threaten to destroy tissue is called "nociception". The weight of evidence indicated that nociception depends on its own sensory receptors, i.e., nociceptors. They are supplied by both small myelinated Aδ fibers and unmyelinated C fibers. There are four different categories of nociceptors, i.e., mechanical, thermal, mechano-thermal and mechanothermochemical (polymodal) nociceptors. Endogenous algogenic substances such as bradykinin activate only polymodal nociceptive fibers. Prostaglandins E2 and I2 sensitize nociceptors.
Nociceptor
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Capsaicin
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Capsaicin selectively excites C-polymodal nociceptors in mammalian skin. In the rat, the only species so far studied in detail, a long-term desensitization of a subpopulation of C-polymodal nociceptors occurs after the initial excitation. After nerve treatment, permanent loss of some C-polymodal nociceptors is found in the rat. It is argued that capsaicin must act primarily on C fibres involved in signalling about pain and not itch, although there may be overlap between the C afferents involved in these two nociceptive sensations. The possibility is raised that C mechanoreceptors, with their good histamine sensitivity, are also involved in itch.
Capsaicin
Nociceptor
Mechanoreceptor
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Capsaicin
Subcutaneous injection
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The responsiveness to noxious thermal, mechanical, and chemical stimuli was examined in adult rats that had been treated neonatally with capsaicin. A range of capsaicin doses was employed to determine whether the neurotoxicity of capsaicin to primary afferent fibers would be manifested behaviorally in a selective effect on nociceptive thresholds to specific stimuli. Animals were given 5 to 100 mg/kg of capsaicin at 2 days of age and were examined 2 to 4 months later using the tail flick and hot plate tests to determine thermal thresholds, the paw pressure test to determine mechanical thresholds, and the formalin test to determine chemical thresholds. Significant impairments of treated animals' responses to all three types of stimuli were found at high doses of capsaicin and at doses which seem to lead to the depletion of only unmyelinated primary afferent fibers. Slightly higher doses of capsaicin were required to increase thermal nociceptive thresholds in the tail flick test as compared with the other tests, and mechanical nociception seemed to be the most sensitive to the effects of capsaicin. At any particular dose of capsaicin, considerable variability was found in the responsiveness of animals to noxious stimuli. This may partly explain the inconsistencies in studies of nociceptive thresholds in capsaicin-treated animals. The results also demonstrate the difficulty of correlating the degree of analgesia exhibited by these animals with the extent of loss of primary afferent fibers or with the depletion of afferent putative peptide transmitters.
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Nociceptor
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Capsaicin is a well-known excitant of cutaneous C-fibre nociceptors. In addition it has long-lasting effects on the functions of C-afferents in the rodent. Administration of capsaicin to neonatal rats causes a large reduction in the number of all functional classes of afferent C-fibre (Carpenter & Lynn 1983; Lynn 1984). We have now examined the effects of direct application to cutaneous nerves in adult animals and have found dramatic and selective effects on axonal conduction and nociceptor function.
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Nociceptor
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Capsaicin
Tail flick test
Hot plate test
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The antinociceptive effect of capsaicin to noxious chemical stimuli has been invariably verified. As to thermal or mechanical nociception, however, routine pharmacological methods resulted in conflicting findings. Therefore, using new techniques the nociceptive thresholds of different stimuli were determined on the hindpaw of the rat. After systemic (400 mg/kg s.c.), perineural (1% on the sciatic nerve) and local (5 micrograms into the hindpaw) application of capsaicin the threshold for noxious heat (47.4 +/- 0.08) was shifted upwards by 3.3 degrees C, 4.1 degrees C and 2.9 degrees C, respectively. The changes in mechanonociceptive threshold evoked by pin prick (186 +/- 9 mN force) were more variable. The response to percutaneous xylene application was abolished or markedly inhibited. After systemic application the responsiveness to noxious heat recovered faster than the effect of xylene. C-polymodal nociceptors and some A-delta mechanoheat-sensitive nociceptors isolated from the saphenous nerve of the rat were activated by capsaicin in nanogram doses given close arterially. Five micrograms capsaicin excited few slowly adapting A mechanoreceptors after a long latency, but not A-delta mechanonociceptors or other cutaneous receptors. Proportion of C-polymodal nociceptors was decreased, that of the C-mechanoreceptors was increased after systemic treatment. The role of polymodal-type nociceptors, interaction of other nociceptors, as well as secondary dynamic changes are stressed to explain the antinociceptive effect of capsaicin.
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Nociceptor
Saphenous nerve
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