The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro

Abstract

The selective excitant and neurotoxic action of capsaicin on vagal sensory neurons in the rat has been investigated in vitro using three techniques: extracellular recording of compound spike potentials from the whole nerve; intracellular recording from ganglion cells using single-electrode current and voltage clamp; and electron microscopy of the nerve and nodose ganglion. Capsaicin (0.1–10 μM) depolarized vagal sensory C fibres and cell bodies, and produced an increased conductance. The conductance increase appeared to be due to an increased permeability to sodium and calcium, plus a secondary increase in potassium (and perhaps chloride) conductance consequent upon calcium entry. The early entry of calcium seems to be a significant priming event in the neurotoxic process, since dramatic ultrastructural changes take place within a few minutes of capsaicin application, which are minimized by removing extracellular calcium ions. The observations indicate that in sensory C neurons capsaicin opens a conductance of limited specificity and that a resultant large calcium entry is closely involved in the rapid development of cell injury.