Abstract: Objective To explore the influence and mechanism of botulinum toxin A on chronic neurogenic pain.Methods Wistar rats were randomly divided into control group, sham group,pain model group (the left L5 and L6 nerves of rats were ligated,after 3 daythe left was injected with normal saline from ipsilateral plantar subcutaneous.) and botulinum toxin treatment group (the left L5 and L6 nerves of rats were ligated, after 3 day the left was injected with 30U/kg BoNT-A from ipsilateral plantar subcutaneous). The botulinum toxin treatment group was further divided into 1d, 3d and 1w group according to the execution time. The cell morphology changes were observed by HE staining.The protein and mRNA expression levels of substance P (SP),interleukin6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical method,in-situ hybridization and real-time quantitative PCR.Results HE staining showed spinal cord inflammatory cells infiltration after SNL rats. Inflammatory infiltration degree was aggravated in the spinal cord as the extension of the ligation time.Protein and mRNA expression levels of SP, IL-6 and TNF-α were significantly higher in pain model 1d,3d and 1w group than that incontrol group (P<0.05).But those were lower in botulinum toxin treatment group at 1d,3d and 1w than that inpain model group (P<0.05) as determined by immunohistochemistry,in-situ hybridization and real-time quantitative PCR.Conclusions Neurotransmitter SP and inflammatory mediators IL-6 and TNF-α were involved in the analgesic effect of BoNT-A on chronic neurogenic pain.