Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X(3)(vol 407, pg 1015, 2000)

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensatio n of pain(1). The ATP receptor P2X(3) is selectively expressed by nocicepto rs(2,3) and is one of seven ATP-gated, cation-selective ion channels(4-6). Here we demonstrate that ablation of the P2X3 gene results in the loss of r apidly desensitizing ATP-gated cation currents in dorsal root ganglion neur ons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behaviour al responses to noxious mechanical and thermal stimuli are also normal, alt hough formalin-induced pain behaviour is reduced. Incontrast, deletion of t he P2X(3) receptor causes enhanced thermal hyperalgesia in chronic inflamma tion. Notably, although dorsal-horn neuronal responses to mechanical and no xious heat application are normal, P2X(3)-null mice are unable to code the intensity of non-noxious 'warming' stimuli.