Sophocarpine Attenuates Chronic Constriction Sciatic Nerve Injury-induced Neuropathic Pain in Mice by Inhibiting the HMGB1/TLR4/NF-κB Signaling Pathway

Background: Sophocarpine (SC) is a major alkaloid extracted from Sophora alopecuroides L. Our previous study showed that SC has analgesic effects on neuropathic pain induced by chronic constriction injury (CCI). However, the exact analgesic mechanism of SC on neuropathic pain has not yet been elucidated. Objectives: The current study aimed to examine the anti-neuropathic pain effects of SC on the HMGB1/TLR4/NF-κB signaling pathway to explore its analgesic mechanism in neuropathic pain. Methods: In this experimental study, the neuropathic pain mouse model was established by CCI of the sciatic nerve in a university-affiliated animal lab, China, 2016. Mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), cold withdrawal threshold (CWT), and tail-curling latency (TCL) were used to assess the antinociceptive effect of SC in neuropathic pain mice. The mRNA and protein expression levels of HMGB1, TLR4, NF-κB, p-NF-κB, TNF-α, and IL-6 in the spinal cord of neuropathic pain mice were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Results: Treatment with 40 and 20 mg/kg of SC was effective in increasing MWT, lengthening TWL, reducing CWT, and prolonging TCL in mice with neuropathic pain induced by CCI. Compared to the neuropathic-pain model group, treatment with 40 mg/kg of SC could effectively down-regulate HMGB1, TLR4, NF-κB, p-NF-κB, TNF-α, and IL-6 mRNA and protein expression levels in the spinal cord of mice with neuropathic pain induced by CCI. Conclusions: Our results showed that SC has analgesic effects on neuropathic pain induced by CCI, and its analgesic mechanism may be related to down-regulating the HMGB1/TLR4/NF-κB signaling pathway.