Modulatory roles of the adenosine triphosphate P2x-purinoceptor in generation of the persistent nociception induced by subcutaneous bee venom injection in the conscious rat.

To study the role of adenosine triphosphate (ATP) P2x-purinoceptor in the persistent nociceptive response induced by subcutaneous (s.c.) bee venom injection, we used a selective P2x receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), to evaluate whether spinal P2x receptor play a role in development of spontaneous persistent pain. Injection s.c. of bee venom into the plantar surface of one hindpaw in the conscious rat produces a monophasic, prolonged persistent nociception characterized by continuously flinching reflex of the injected paw for 1-2 h. Intrathecal (i.t.) pretreatment with PPADS at two lower doses of 5 and 10 microg resulted in suppression of the flinching reflex in a dose dependent manner with the inhibitory rate 37 and 44%, respectively, when compared with the control group; whereas i.t. PPADS at a higher dose of 30 microg failed to produce any inhibitory effect. This result suggests that activation of P2x-purinoceptor in the spinal cord contributes to the induction of bee venom-induced prolonged persistent pain. However, the antinociceptive effect of ATP P2x-purinoceptor antagonist such as PPADS on clinical pathological pain seems to be limited due to its lack of effectiveness at higher dose.