<p>Sanguinarine Attenuates Neuropathic Pain by Inhibiting P38 MAPK Activated Neuroinflammation in Rat Model</p>
Chao Yu, Ping Li, Yanxiu Wang, Kaigang Zhang, Zuncheng Zheng, Lishuang Liang
Abstract
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.