Selective P2X7 Antagonists

See For Examples;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721772/

A more recent study has demonstrated that P2X7 knockout mice show reduced pain sensitivity following both complete Freund’s adjuvant-induced inflammation and partial injury of the sciatic nerve [32].

 

These data were consistent with the mechanistic role of P2X7 receptors in modulating IL-1β release and the ability of IL-1β to alter pain sensitivity in experimental models.

 

It has been shown, for example, that increased IL-1 levels are associated with enhanced nociceptive signaling in a concentration-related fashion [33, 34].

The P2X7 receptor has also been linked with release of the excitatory neurotransmitter glutamate, well-known for its involvement in pain transmission. In hippocampal slices from P2X7 KO mice, ATP-evoked release of [3H]glutamate was virtually absent, in contrast to the robust neurotransmitter release observed with wild-type controls [35].

 

Under electrical stimulation, [3H]glutamate release was also significantly attenuated in the KO animals, although some level of residual release was present. These observations are consistent with results implicating the participation of P2X7 in excitatory amino acid release from murine astrocytes [36].

 

The potential role of P2X7 in modulating glutamate release thus provides an additional rationale for the reduced nociceptive responses of the P2X7 KO mice under chronic inflammation or nerve injury conditions.

 

In view of the participation of P2X7 in the release of IL-1β and glutamate, the localization of P2X7 receptors on glial cells, and the growing appreciation for the role of activated glia in promoting the development and maintenance of pathological pain [37–39], it is tempting to regard the P2X7 receptor as a central player in this neuroimmune interface.