PT - JOURNAL ARTICLE AU - Boris A. Chizh AU - Peter Illes TI - P2X Receptors and Nociception DP - 2001 Dec 01 TA - Pharmacological Reviews PG - 553--568 VI - 53 IP - 4 4099 - http://pharmrev.aspetjournals.org/content/53/4/553.short 4100 - http://pharmrev.aspetjournals.org/content/53/4/553.full SO - Pharmacol Rev2001 Dec 01; 53 AB - The potential importance for nociception of P2X receptors, the ionotropic receptors activated by ATP, is underscored by the variety of pain states in which this endogenous ligand can be released. Several important findings have been made recently indicating that P2X receptors can be involved in pain mechanisms both centrally and in the periphery. The roles of ATP at these two sites and the P2X receptor subtypes involved appear to be different. In the periphery, ATP can be released as a result of tissue injury, visceral distension, or sympathetic activation and can excite nociceptive primary afferents by acting at homomeric P2X3 or heteromeric P2X2/3receptors. Centrally, ATP released from central afferent terminals or second order neurons can modulate neurotransmitter release or postsynaptically activate neurons involved in central nociceptive transmission, with P2X2, P2X4, P2X6, and some other receptors being potentially involved. Evidence from in vivo studies suggests that peripheral ATPergic mechanisms are most important under conditions of acute tissue injury and inflammation whereas the relevance of central mechanisms appears to be more limited. Furthermore, the release of ATP and P2X receptor-mediated afferent activation appear to have been implicated in visceral and neuropathic pain; the importance of the ATPergic component in these states needs to be investigated further. Thus, peripheral P2X receptors, and homomeric P2X3 and/or heteromeric P2X2/3 receptors in particular, constitute attractive targets for analgesic drugs. The development of selective antagonists of these receptors, suitable for a systemic in vivo use although apparently difficult, may prove a useful strategy to generate analgesics with a novel mechanism of action.