The data reviewed in this article suggest that protons should no longer be considered simply as an unwanted by-product of anaerobic respiration that results from either an accumulation of inflammatory cells or a reduced oxygenated blood supply during ischaemia. A fall in extracellular pH can stimulate a subpopulation of sensory nerves by activation orion channels. The available evidence indicates that most, if not all, of the activated neurones are also stimulated by capsaicin, and that protons and capsaicin share a common mechanism of neuronal activation. A proton should be viewed as a mediator that elicits a protective response with reflex cardiovascular and respiratory responses, which modulate systemic blood flow, and with the local release of sensory neuropeptides, which vasodi/ates the microvascu/ature and stimulates extravasation.

Neuropharmacological research with the excitotoxin capsaicin has resulted in the discovery of a subpopulation of primary sensory neurones that is sensitive uniquely to this drug. Capsaicin at first excites and then functionally desensitizes some thinly myelinated AS as well as unmyelinated C fibres; some of these nerves innervate somatic regions, while others innervate the viscera. The sensitivity of nerves to capsaicin has been used as a marker to classify this type of afferent 1-3, and endogenous, as well as other exogenous agents that act on these nerves, can now be investigated. Studies of the actions of various agents suggest that protons are unique activators of capsaicin-sensitive nerves.