Sanguinarine Attenuates Neuropathic Pain by Inhibiting P38 MAPK Activated Neuroinflammation in Rat Model

Chao Yu,1,2,* Ping Li,3,* Yan-Xiu Wang,2 Kai-Gang Zhang,4 Zun-Cheng Zheng,3 Li-Shuang Liang5 1Department of Pain Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Pain Medicine, Taian City Central Hospital, Tai’an, Shandong, People’s Republic of China; 3Department of Physical Medicine and Rehabilitation, Taian City Central Hospital, Tai’an, Shandong, People’s Republic of China; 4Department of Orthopaedic Surgery, Taian City Central Hospital, Tai’an, Shandong, People’s Republic of China; 5Department of Pain Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Shuang LiangDepartment of Pain Medicine, Qilu Hospital of Shandong University, 44 Wenhua West Road, Jinan, Shandong Province 250012, People’s Republic of ChinaTel/Fax +86 13561764131Email liangls1224@163.comKai-Gang ZhangDepartment of Orthopaedic Surgery, Taian City Central Hospital, No. 29 Long Tan Road, Taian, Shandong 271000, People’s Republic of ChinaTel/Fax +86 15264832232Email zhangkg0308@yeah.netBackground: 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.Keywords: sanguinarine, neuropathic pain, inflammatory cytokines, NF-kB, p38MAPK