ATP as a peripheral mediator of pain

This article reviews the extent to which recent studies substantiate the hy pothesis that ATP functions as a peripheral pain mediator. The discovery of the P2X family of ion channels (for which ATP is a ligand) and, in particu lar, the highly selective distribution of the P2X(3) receptor within the ra t nociceptive system has inspired a variety of approaches to elucidate the potential role of ATP as a pain mediator. ATP elicits excitatory inward cur rents in small diameter sensory ganglion cells. These currents resemble tho se elicited by ATP on recombinantly expressed heteromeric P2X(2/3) channels as well as homomultimers consisting of P2X(2) and P2X(3). In vivo behaviou ral models have characterised the algogenic properties of ATP in normal con ditions and in models of peripheral sensitisation. In humans, iontophoresis of ATP induces modest pain. In rats and humans the response is dependent o n capsaicin sensitive neurons and is augmented in the presence of inflammat ory mediators. Since ATP can be released in the vicinity of peripheral noci ceptive terminals under a variety of conditions, there exists a purinergic chain of biological processes linking tissue damage to pain perception. The challenge remains to prove a physiological role for endogenous ATP in acti vating this chain of events. (C) 2000 Published by Elsevier Science B.V. Al l rights reserved.