Effect of tetramethylpyrazine on acute nociception mediated by signaling of P2X receptor activation in rat.

Tetramethylpyrazine (TMP) has been used in traditional Chinese medicine as an analgesic for dysmenorrhea. In the present study, we try to investigate the effects of TMP on acute nociception mediated by P2X receptor activation of rat hindpaw and the membrane depolarization of rat dorsal root ganglion (DRG) neurons induced by P2X receptor agonists. The subcutaneous administration of TMP (0.1-10 mmol) into rat hindpaw in a dose-dependent manner decreased acute paw flinching responses mediated by adenosine 5'-triphosphate (ATP, 1000 nmol) or alpha,beta-methylene ATP (alpha,beta-meATP, 600 nmol). The subcutaneous administration of TMP (5 or 10 mmol) into rat hindpaw inhibited significantly the first phase of nociceptive behaviors induced by 5% formalin and attenuated slightly the second phase of nociceptive behaviors induced by 5% formalin. The subcutaneous administration of TMP (10 mmol) into rat hindpaw reduced the nociceptive responses induced by alpha,beta-meATP (200 nmol) co-injected with Prostaglandin E2 (PGE2), 5 micromol). The membrane depolarization induced by ATP (200 micromol) or alpha,beta-meATP (50 micromol) in DRG neurons was inhibited by TMP (300 micromol). The data suggest that the antinociceptive effect of TMP is involved in blocking the signaling of P2X3 receptor activation in rat.