The Roles Of P2x Receptors And NK Receptors In Bee Venom Induced Pathological Pain

Pathological pain is a common clinical symptom characterized by a persistent spontaneous pain and hyperalgesia. To unravel the mechanisms of pathological pain, the bee venom model was used to evaluate the roles of P2x receptor and NK receptor in development of pathological pain. The bee venom model is a novel pathological pain model characterized by containing not only a persistent spontaneous pain process but also a long term hyperalgesia (including primary thermal and mechanical hyperalgesia and secondary thermal hyperalgesia). This model mimics clinical pathological pain well and was found to be superior to the traditional pain models such as the formalin test and capsaicin model, etc. P2x receptor is ligand-gated ion channels. Until now seven subtypes of its family have been cloned and ATP act as its endogenous agonist. NK receptor is G-protein coupled receptor which consist of NK1, NK2, NK3 receptor. SP, NKA and NKB are their endogenous agonists respectively. P2x and NK receptor distributed extensively in the central and peripheral nervous system and different subtype have distinct feature of their location. Previous studies have proved that both receptor mediate the transmission of nociceptive information. But it still remain unclear that whether they play the same role in the nociception with different characteristics. In this study, behavioral observation was adopted to evaluate the role of spinal and non-spinal P2x receptor and spinal NK receptor in bee venom induced pathological pain, and three classes of results were obtained.1. The role of spinal P2x receptor in bee venom induced persistent spontaneous painP2x receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), was intrathecally applied. 15 minutes later, bee venom (0.2 mg/50 ul) wasinjected into the plantar surface of one hindpaw. It was shown that PPADS at 5 and 10 ug produced a dose dependent inhibitory effect on bee venom induced spontaneous nociception. While PPADS 30 ug failed to produced any effect.2. The role of peripheral P2x receptor in the bee venom induced spontaneous pain and hyperalgesiaFive minutes before s.c. bee venom injection, PPADS (20, 40 nmol/50 ul) was administered into the plantar surface of the hindpaw. It was found that both doses of PPADS inhibited the spontaneous nociception. And there was no significance between the inhibitory effect of the two doses. Two hour after bee venom, the threshold to mechanical stimulation and the latency to thermal stimulation was measured, and it was found that PPADS produced no effect on the primary mechanical hyperalgesia, while it attenuated the thermal hyperalgesia dose dependently. Secondary thermal hyperalgesia was not influenced.3. The roles of spinal NK receptor in bee venom-induced spontaneous pain and hyperalgesiaNon-selective NK1/2 receptor antagonist, spantide (0.05, 0.5, 5 jug), was applied intrathecally 5 minutes before bee venom injection. It was shown that spantide produced a dose-dependent inhibitory effect on the bee venom induced spontaneous response. Spantide at 5 (ag also reduced primary and secondary thermal hyperalgesia. But the mechanical hyperalgesia was not influenced. Spontaneous pain was also inhibited by intrathecal application of spantide 5 minutes after bee venom. And the drug take effect within about 5 minutes. In the controlling group, spantide was intrathecally applied 3-4 hour after bee venom, and it did not produce any reversing effect on the thermal and mechanical hyperalgesia.Pre-treatment of SRI42801(40, 65 ug) 5 minutes after bee venom (0.2 mg/50 ul)failed to inhibit the spontaneous pain and hyperalgesia induced by bee venom injection. The spontaneous pain was not influenced by post-treatment of SRI42801 (40 ug) 5 minutes after bee venom. In the controlling group, SRI42801 was intrathecally applied 3-4 hour after bee venom, and.it did not produce any reversing effect on the thermal and mechanical hyperalgesia.Conclusions1) Spinal P2x receptor participate in the induction of the bee venom i...