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 mu g 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 mu g 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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.