Capsaicin, the main pungent ingredient in 'hot' chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system We have used an expression cloning strategy based on calcium influx to isolate a functional cDNA encoding a capsaicin receptor from sensory neurons This receptor is a non-selective cation channel that is structurally related to members of the TRP family of ion channels The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo

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The capsaicin receptor: a heat-activated ion channel in the pain pathway

http://www.columbia.edu/cu/biology/courses/w3004/recitation7.pdf

The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli

A novel peptide, calcitonin gene-related peptide (CGRP), has been predicted to result from alternative processing of the primary RNA transcript of the calcitonin gene in the rat. Several lines of evidence suggest that CGRP is a transmitter in the central and peripheral nervous system. Human CGRP has been isolated and characterized, and shown to have potent effects on the heart. The observations presented here indicate that human and rat CGRP also have potent effects on blood vessels. Intradermal injection of CGRP in femtomole doses induces microvascular dilatation resulting in increased blood flow, which we have detected in the rabbit by using a 133Xe clearance technique. In human skin, CGRP induces persistent local reddening. Microscopic observation of the hamster cheek pouch in vivo revealed that topical application of CGRP induces dilatation of arterioles. Furthermore, CGRP relaxes strips of rat aorta in vitro by an endothelial cell-dependent mechanism. Therefore, we suggest that local extravascular release of CGRP may be involved in the physiological control of blood flow and that circulating CGRP may contribute to hyperaemia in certain pathological conditions.

Calcitonin gene-related peptide is a potent vasodilator

Natural products afford a window of opportunity to study important biology. If the natural product is used or abused by human beings, finding its biological target(s) is all the more significant. Hot pepper is eaten on a daily basis by an estimated one-quarter of the world’s population and

Vanilloid (Capsaicin) Receptors and Mechanisms

Wasabi, horseradish and mustard owe their pungency to isothiocyanate compounds Topical application of mustard oil (allyl isothiocyanate) to the skin activates underlying sensory nerve endings, thereby producing pain, inflammation and robust hypersensitivity to thermal and mechanical stimuli Despite their widespread use in both the kitchen and the laboratory, the molecular mechanism through which isothiocyanates mediate their effects remains unknown Here we show that mustard oil depolarizes a subpopulation of primary sensory neurons that are also activated by capsaicin, the pungent ingredient in chilli peppers, and by Delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana Both allyl isothiocyanate and THC mediate their excitatory effects by activating ANKTM1, a member of the TRP ion channel family recently implicated in the detection of noxious cold These findings identify a cellular and molecular target for the pungent action of mustard oils and support an emerging role for TRP channels as ionotropic cannabinoid receptors

Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1

PHARMACOLOGICALLY evoked selective degeneration of neurones with a specific function or functioning with known transmitter substances, has been reported only in the monoaminergic neurone systems1,2. We report here that selective degeneration of neurones with a highly specific function can be produced by chemical agents in the somatosensory system as well. Capsaicin given to newborn rats induces selective degeneration of a distinct population of primary sensory neurones involved in mediation of chemogenic pain.

Aurelia Jancsó-Gábor

Papers

Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones