Marsh, Stephen John; (1991) The mechanism of action of capsaicin on sensory C-type neurones and their axons in vitro. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The mechanism of action of the sensory neurotoxin, capsaicin, on visceral afferent fibres and ganglion cells has been studied using electrophysiological and histological techniques. Extracellular in vitro recording from adult vagus nerves revealed a depolarization and a reduced C-spike amplitude. These probably reflect effects on unmyelinated sensory fibres, since no such action was detected in fibre trunks lacking sensory fibres, such as preganglionic sympathetic nerves and ventral spinal roots. Ion substitution experiments indicated that the capsaicin-induced depolarization is mediated by a mechanism that involves sodium (Na+) calcium (Ca2+) and, to a lesser extent chloride, (Cl-) ions. In vitro intracellular recordings from sensory neurone perikarya, showed that capsaicin depolarizes 70% of the C-type neurones located within the rat nodose ganglion. The capsaicin-induced depolarization was primarily mediated by an increase by an in membrane conductance to Na+ and Ca2+. An additional membrane conductance increase to potassium (K+) was also induced. However, this depended on an influx of calcium via the primary conductance mechanism. Histological experiments using light and electron-microscopic techniques indicated that capsaicin can induce substantial cytotoxic damage to a subpopulation of nodose sensory neurones and vagus nerve unmyelinated fibres. Moreover, the cytotoxic effects could be induced by short applications (< 10 mins) and low concentrations (1-10 μM) of capsaicin. The entry of calcium ions into the cells appeared to play a major role in the cytotoxic process, as the replacement of extracellular calcium with magnesium minimised the cytotoxic damage. The failure of calcium channel-blockers to reduce the calcium-dependent neurotoxic effect indicated that calcium entry through capsaicin-activated channels, rather than voltage-gated calcium channels, initiates the cytotoxicity. It is suggested that capsaicin opens cationic channels and that calcium entry through these channels might not only modify cell excitability but also prime the neurotoxic process which can lead to cell death.

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