VEGF Participated In Neuropathic Pain Through Regulating NK-1Mediated By ERK Signaling Pathway In CCI Rats

ObjectIn order to investigate VEGF signaling pathway contributes to chronic constrictive injury-induced neuropathic pain in rats and related mechanisms, it was researched that the effects of VEGF antibody and U0126(a MEK inhibitor) on the pain thresholds, the expressing of p-ERK and NK-1in the spinal cord in CCI rats respectively.MethodsThirty-five SD rats were divided into seven groups randomly. The rats in control group were normal rats. The rats in CCI group received an operation of ligation of left sciatic nerve. The rats in shame group received exposure of left sciatic nerve without ligation. The rats in VEGF antibody group received intrathecal injection of VEGF antibody after CCI. The rats in normal saline menstruum group received intrathecal injection of normal saline after CCI. The rats in U0126group received intrathecal injection of MEK inhibitor after CCI. The rats in DMSO menstruum group received intrathecal injection of5%DMSO after CCI.Results1. There is no difference in the basic PWMT or PWTL of the rats between each group (P>0.05). The rats in shame group and control group have no difference in PWMT and PWTL (P>0.05). The PWMT and PWTL of the rats in CCI group decreased significantly compared with that in control group,(P<0.05). There was a decrease of PWMT and PWTL significantly in VEGF antibody group and U0126group compared with that in any other groups (P<0.05).2. The results of immunohistochemistry:There is no difference in the expression of p-ERK and NK-1in spinal dorsal horn in Seventh Day between control group and shame group (P>0.05), and the expression of p-ERK and NK-1in spinal dorsal horn in CCI group, VEGF antibody group, U0126group and menstruum group increased significantly compared with that in control group and shame group (P<0.05). The expression of p-ERK and NK-1in spinal dorsal horn in VEGF antibody group and U0126group decreased significantly compared with that in CCI group and menstruum group(P<0.05).3. The results of western-blot: The expression of p-ERK and NK-1in spinal dorsal horn in CCI group, VEGF antibody group, U0126group and menstruum group was significantly higher than that in control group and shame group (P<0.05). The expression of p-ERK and NK-1in spinal dorsal horn in VEGF antibody group and U0126group was significantly lower than that in CCI group and menstruum group(P<0.05).ConclusionThe results suggest that VEGF and ERK signaling pathway may involve in neuropathic pain in CCI rats. It may plays an important role in VEGF involved in neuropathic pain that upregulation of NK-1mediated by ERK signaling pathway in spinal cord neurons.