Fig. 6. Effect of the P2X3 receptor antagonist A-317491 on hyperalgesia induced by compound 48/80 and GTN.
We hypothesized that mediator(s) released from mast cells act on endothelial cells (see Fig. 5) to release ATP, which, in turn, can act at P2X3 receptors on primary afferent nociceptors, to produce mechanical hyperalgesia. Pretreatment with the selective P2X3 receptor antagonist, A-317491 markedly attenuated hyperalgesia produced by acute administration of compound 48/80 (10 µg intradermal in the hind paw; one-tailed Student’s t-test, P<0.0001, Panel A), as well as the delayed onset hyperalgesia induced by the administration of GTN (one-tailed Student’s t-test, P<0.0001, Panel B).