Intrathecal Injection Of JWH-015 Inhibits Inflammatory Mediators Of NR2B Activation Of Neuropathic Pain

Objective: We will examine whether CB2 receptor agonist JWH-015 inhibits CCI-induced neuropathic pain.At the same time,we observed the time course of activation of CB2 receptor and NR2 B in DRG and dorsal horn of spinal cord,the effect of CB2 receptor agonist JWH-015 and inhibitor AM630 on the thermal pain threshold and the changes of DR2 B and spinal cord NR2 B.Methods: Create a rat sciatic nerve ligation(CCI)model,and after the success of rats intrathecal tube,divided 48 male SD rats into 4 groups randomly,sham operation group(Group sham)and only exposed the sciatic nerve(group CCI),ligation in the rats' Sciatic nerve,DMSO liquid injection only 10 g/ day for 7 days;group F,affter CCI,intrathecal injection of CB2 agonist JWH-015,10 g/ day for 7 days;group P,affter CCI,inject CB2 receptor inhibitor AM630 before the injection of JWH-015 in half an hour.Determine the heat pain threshold of rats after 3 days,7 days and 14 days respectively,and Using immunohistochemistry and western blot assay the expression of NB2 B and inflammatory factors.Results:1 : Compared with the sham group,the thermal pain threshold was significantly decreased(P <0.05)at each time point in the CCI group,and the pain threshold was significantly higher in the CCI group than in the CCI group(P <0.05)<0.05).However,in the P group,the CB2 receptor antagonist AM630 was injected into the CB2 receptor agonist before the pre-injection of the CB2 receptor antagonist,and the thermal pain threshold at the time point of each group was not significantly changed compared with the sham operation group,indicating that pre-intrathecal injection of AM-630,the effect of CB2 receptor agonist JWH-015 was ineffective.2:Effects of CCI on TNF-? and IL-1? in dorsal horn of spinal cord in rats: The expression of TNF-? and IL-1? in spinal dorsal horn after sciatic nerve ligation increased significantly.Both of these methods demonstrated this phenomenon.Immunohistochemistry The expression of TNF-? and IL-1? in spinal dorsal horn after CCI detection was significantly higher than that in sham operation group(P <0.05),and the expression of TNF-? and IL-1? in CCI group was significantly higher than that in sham operation group The expression of TNF-? and IL-1? in spinal cord was significantly increased after CCI expression.However,JWH-015 was injected intrathecally after CCI model to inhibit the expression of TNF-? and IL-1? after CCI model,and this effect was impaired after pre-injection of AM630.3:The effect of CCI on NR2 B in spinal dorsal horn of rats: the expression of NR2 B in spinal dorsal horn after sciatic nerve ligation was significantly increased.The expression of NR2 B in spinal dorsal horn after CCI was detected by Western blot.Compared with sham group,(P <0.05).However,JWH-015 was injected intrathecally after CCI model,which could inhibit the expression of NR2 B after CCI model,and this effect was impaired after pre-injection of AM630.Conclusion: 1:The levels of TNF-?,IL-1? and NR2 B in spinal cord of rats after CCI were significantly higher than those in sham operation group,and inflammatory response was significantly enhanced.TNF-?,IL-1? and NR2 B were involved in neuropathic pain.2:Intrathecal JWH-015 can effectively reduce the neuropathic pain caused by CCI model,and the DRG and spinal TNF-?,IL-1? and NR2 B in rats with intrathecal injection of JWH-015 are significantly decreased.3:The effect of JWH-015 was ineffective after intrathecal injection of AM-630.4 : JWH-015 is a neuropathic pain caused by inhibition of inflammatory mediator-mediated NR2 B activation to further inhibit the CCI model.