Background: Neuropathic pain seriously affects life quality, and it is urgent to develop novel drugs with high efficacy and few side effects. Sanguinarine (SG) is a natural plant medicine with anti-inflammatory and neuroprotection effects. This study aimed to investigate the effect of SG on chronic constriction injury (CCI)-induced neuropathic pain. Materials and Methods: CCI rat model was established and rats were randomly divided into sham group, sham + SG group (6.25 mg/kg), CCI group, CCI + SG group (1.00, 2.50 and 6.25 mg/kg). The mechanical sensitivity and heat hypersensitivity of rats were monitored at different time points. Immunohistochemical, PCR, Western blot and ELISA were used to analyze p-p38 MAPK, NF-κB p65, TNF-α, IL-1β, and IL-6 levels. Results: The mechanical sensitivity and heat hypersensitivity significantly reduced in rats of CCI group, but significantly increased in rats of CCI+SG group. TNF-α, IL-1β, and IL-6 levels significantly increased in the spinal cord of CCI rats, but significantly decreased in rats of CCI+SG group. In addition, p38 MAPK activator antagonized beneficial effects of SG on neuropathic pain. Overexpression of p38 MAPK reduced the mechanical sensitivity and heat hypersensitivity, and enhanced NF-κB activity and the expression of inflammatory factors in CCI rats. Conclusion: SG alleviates neuropathic pain via suppressing p38MAPK signaling and downregulating the expression of TNF-α, IL-1β, IL-6 and NF-κB activation. SG may be a potential therapeutic agent to treat neuropathic pain.

Objective. There is still no effective treatment of neuropathic pain. Sanguinarine is a natural plant medicine with anti‐inflammatory effects, but its effect on neuropathic pain remains unclear. This study was aimed at investigating the potential of sanguinarine to attenuate neuropathic pain. Methods. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Rats were randomly divided into several groups: sham, CCI, CCI+SG (1.00 mg/kg), CCI+SG (2.50 mg/kg), and CCI+SG (6.25 mg/kg). SG was injected intraperitoneally from the day of surgery every three days. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded before surgery and on days 1, 3, 7, and 14 after surgery. The microglia in the spinal dorsal horn were examined by immunofluorescence. p38 MAPK expression in the spinal dorsal horn was detected by PCR and Western blot analysis. Cytokine levels in the spinal dorsal horn were measured by ELISA. Results. MWT and TWL were significantly reduced in the CCI group, but sanguinarine recovered MWT and TWL in the CCI group. In addition, sanguinarine inhibited the activation of microglia and decreased the expression of p‐p38 and TNF‐α, IL‐1β, and IL‐6 in the spinal dorsal horn of the CCI group in a dose‐dependent manner. Conclusions. Our results suggest that sanguinarine can attenuate neuropathic pain via inhibiting the activation of microglia and the activation of the p38 MAPK signaling pathway.

Spinal cord injury (SCI) as a serious neurological disease remains the great challenge for clinical therapy. Existing studies have confirmed that selenium (Se) supplementation could effectively decrease the risk of neurological diseases, but the mechanism is still unclear. Herein, a mouse SCI model was established, and the potential of selenomethionine (SeMet) against SCI was explored. Behavioral studies showed that SeMet administration in vivo effectively improved the motor symptoms of SCI mice. Mechanism investigation indicated that SeMet administration in vivo significantly blocked the decrease of neurons and Nissl bodies in SCI mice by inhibiting neural apoptosis. SeMet in vivo also dramatically attenuated oxidative damage of SCI mice by regulating the Nrf‐2/Keap‐1 pathway. Further studies revealed that SeMet in vivo significantly alleviated microglia activation and neuroinflammation in SCI mice, as demonstrated by the improved Iba‐1 and inflammatory factors expression, respectively. Moreover, SeMet in vivo apparently inhibited SCI‐induced cell ferroptosis of SCI mice by balancing ferroptosis‐related protein expression. Taken together, the results indicated that oxidative damage–mediated apoptosis and ferroptosis both contributed to the protective potential of SeMet against SCI, which validated the possibility that selenium‐containing agents could be promising drugs for SCI therapy.