The role of P2X7 in pain and inflammation |
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Authors: | Jane P Hughes Jonathan P Hatcher Iain P Chessell |
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Institution: | (1) Neurology & GI CEDD, GlaxoSmithKline, Third Avenue, Harlow, Essex, CM19 5AW, UK |
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Abstract: | The P2X7 purinoceptor is unique amongst the P2X receptor family in that its activation is able to stimulate the release of mature,
biologically active interleukin-1β (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. |
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Keywords: | cytokines inflammation interleukin-1β pain P2X7 |
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