Change Of HCN4 Channel Expression In Striatum Of Rats With Paclitaxel-induced Neuropathic Pain And Its Relationship With GABA_B Receptor

Objective:To investigate the expression of HCN4 channel in striatum of rats with paclitaxel-induced neuropathic pain and its relationship with GABA_Breceptor.Methods:The male SD rats of clean grade aged 6?9 weeks,weighing180?220g.The model of paclitaxel-induced neuropathic pain was established by intraperitoneal injection of 2 mg/kg of paclitaxel 1,3,5 and 7 days after the experiment.After successful intrathecal catheterization,the rats were randomly divided into 5 groups?n=10?:Paclitaxel model group?P group?,paclitaxel model+saline?N?,paclitaxel model+lentivirus empty vector group?BV group?,paclitaxel model+HCN4 channel lentivirus group?H group?,paclitaxel model+ZD7288 group?I group?,10 rats of the same age as the blank control group?C group?.On the 15th day after intraperitoneal injection,different drugs were intrathecally injected with 20?L:Group N was injected with normal saline,group BV was injected with HCN4 channel lentivirus empty vector?1 X10⁸ TU/ml?,group H was injected with HCN4channel lentivirus?1 X10⁸ TU/ml?,and group I was injected with HCN4channel inhibitor ZD7288?30?g?.The 50%mechanical foot shrinkage threshold?MWT?was measured 1 day before intraperitoneal injection?T₀?,14days?T₁?and 21 days?T₂?after injection.The expression of HCN4 channel and GABA_B receptor in striatum was determined by immunohistochemistry and Western blot 21 days?T₂?after intraperitoneal injection.Results:1?MWT results:Compared with the T₀,MWT decreased in group P,N,BV,H and group I at T₁?P<0.05?;Compared with the T₁,MWT increased in group H and group I at T₂?P<0.05?.Compared with group C,MWT decreased in group P,group N,group BV,group H and group I at T₁?P<0.05?;compared with group P,MWT increased in group H and group I at T₂?P<0.05?.2?Immunohistochemical results:Compared with group C,the expression of HCN4 channel protein increased and GABA_B receptor protein decreased in striatum of group P at T₂?P<0.05?;compared with group P,the expression of HCN4 channel protein decreased and GABA_B receptor protein increased in striatum of group H and group I at T₂?P<0.05?.3?Results of Western blot:Compared with group C,the expression of HCN4 channel protein increased and GABA_B receptor protein decreased in striatum of group P at T₂?P<0.05?;compared with group P,the expression of HCN4 channel protein decreased and GABA_B receptor protein increased in striatum of group H and group I at T₂?P<0.05?.Conclusions:1.Paclitaxel can induce neuropathic pain by down-regulating the expression of GABA_B receptor protein in rat striatum and increasing the expression of HCN4 channel protein.2.Inhibition of HCN4 channel can decrease the expression of HCN4channel protein and increase the expression of GABA_B receptor protein.3.Thus alleviating the neuropathic pain induced by paclitaxel in rats.Therefore,HCN4 channel plays an analgesic role through GABA_B receptor,which can be used as a new target for the treatment of paclitaxel induced neuropathic pain.