Details
Title
Future perspectives of capsaicin research
Author
Szolcsanyi, J.
Imprint
London Taylor & Francis United Kingdom
Publication Date
2003
Description
p.248-270
Call Number
SB348.P46D6
Summary
Capsaicin, the pungent principle in chilli peppers has become a promising molecule for the development of a new generation of analgesic-anti-inflammatory agents with a target molecule on nociceptive primary afferent neurons. The present state of knowledge in this field is summarized in this chapter after a short historical introduction. Furthermore, the horizons of new trends in the peptidergic neuroregulatory functions of these capsaicin-sensitive afferents are outlined. Recently the rat and human capsaicin (vanilloid) VRI receprors have been cloned and identified in one group of sensory neurons. These nociceptive membrane proteins of the TRP superfamily are cation channels gated by noxious heat, protOns, capsaicin, resiniferatoxin and endogenous ligands as anandamide and lipoxygenase products. TRPV channel subtypes with similar structure were cloned from neurons (VRL-l, VR5'sv, VR-OAc) and from non-neural tissues, but none of them were activated by the vanilloid agonists capsaicin or resiniferatoxin. The response characteristics of cell lines transfected with point mutant VRI derivatives as well as nociceptive behaviour and sensory neuron features ofVRl knock out mice are summarized. The role of TRPVI/VRI receptors in inflammatOry pain is emphasized. VRI agonists after prolonged opening of the cation channel induce sensory desensitization of nociceptOrs to all types of stimuli by inducing secondary intracellular changes (dephosphorylation of VRI receptors, inhibition of voltage-gated Ca ++ and Na + channels, mitOchondrial impairment). Sensory desensitization to the pain producing effect of bradykinin in the human skin and at the level of C-polymodal nociceptors is explained by intracellular biochemical changes in VRI expressing nerve terminals. Evidence that capsaicin stimulates then desensitizes the warmth sensors of the hypothalamus is listed. It is suggested that the signal-inducing sensory function and peptidergic efferent functions are coupled at the level of the same capsaicin-sensitive sensory nerve terminals. The excitation-induced release of tachykinins and CGRP elicit local efferent responses as neurogenic inflammation, vasodilatation and various smooth muscle responses. The release of somatostatin from these nerve endings induces systemic anti-inflammatory and analgesic effects ("the sensocrine" function of capsaicin-sensitive nociceptOrs). The pathophysiological relevance of these "unorthodox" regulatOry mecha nisms form promising perspectives for drug development. The possible physiological role of sensory neuropeptides are indicated by the vasodilatory response of CGRP and the anti-inflammatOry effects of somatOstatin released from these capsaicin-sensitive afferents at the subnociceptive level of stimulation.
Book Title
Capsicum: the genus Capsicum
Contact Information
harvest@worldveg.org
Record Appears in
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