The role of P2X₇ in pain and inflammation.
The P2X ₇purinoceptor is unique amongst the P2X receptor family in that its activation is able to stimulate the release of mature, biologically active interleukin-1beta (IL-1β), as well as a variety of other proinflammatory cytokines. Coupled with the predominate localisation of this receptor to immunocytes of haemopoetic origin, this receptor is an obvious candidate to play a major and pivotal role in processes of pain and inflammation. Using genetically modified animals that lack the P2X₇ receptor, several investigators have shown that these mice do indeed demonstrate a blunted inflammatory response, and fail to develop pain following both inflammatory and neuropathic insult. These animals also show altered cytokine production in response to inflammatory stimulus, which is far broader than merely modulation of IL-1β release. In this short article, we review the role of the P2X₇ receptor in modulating the release of cytokines and other mediators, and discuss the findings made from P2X₇ receptor-deficient animals. As well as highlighting outstanding questions regarding this intriguing receptor, we also speculate as to the potential therapeutic benefit of P2X₇ receptor modulation.
Hughes
Jane P
JP
Neurology & GI CEDD, GlaxoSmithKline, Third Avenue, Harlow, Essex, CM19 5AW, UK.
Hatcher
Jonathan P
JP
Chessell
Iain P
IP