Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X(3)receptors

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 P2X(3) gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion ne urons, and that the responses of nodose ganglion neurons to ATP show altere d kinetics and pharmacology resulting from the loss of expression of P2X(2/ 3) heteromultimers. Null mutants have normal sensorimotor function. Behavio ural responses to noxious mechanical and thermal stimuli are also normal, a lthough formalin-induced pain behaviour is reduced. In contrast, deletion o f the P2X(3) receptor causes enhanced thermal hyperalgesia in chronic infla mmation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X(3)-null mice are unable to code t he intensity of non-noxious 'warming' stimuli.