Antihyperalgesic Effect of Paeniflorin Based on Chronic Constriction Injury in Rats

作者：Zhang, Di; Jing, Bei; Li, Xin; Shi, Huimei; Chen, Zhenni; Chang, Shiquan; Zheng, Yachun; Lin, Yi; Pan, Yuwei; Sun, Jianxin^*; Zhao, Guoping^*

来源：Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy, 2022, 32(3): 375-385.

DOI：10.1007/s43450-022-00251-z

• Herbal product
• Network pharmacology Hypersensitivity
• Inflammation
• Inflammatory mediators
• Nociceptor

This study explored paeoniflorin potential to alleviate mechanical pain and cold pain. Behavioral tests were conducted in rats after surgery to evaluate paeoniflorin effect in the pain model, chronic constriction injury of sciatic nerve. After a pharmacological network analysis, it was found that inflammatory mediator regulation of TRP channels was the preferred target for the modulation of chronic neuropathic pain. To verify this result, a series of molecular docking studies with paeoniflorin was conducted. After chronic constriction injuries, rats were sensitized to mechanical hyperalgesia and cold hyperalgesia. The mRNA levels of transient receptor potential cation channels of the subfamily V (vanilloid) 2 (TRPV2) and 3 (TRPV3) and the expression levels of TRPV1 and TRPV4, and those of the subfamilies M (melastatin, TRPM8), A (ankyrin, TRPA1), and phosphorylated p38 mitogen-activated protein kinases (MAPK) increased sharply in the injured animal group. The serum levels of the pro-inflammatory cytokines, such as interleukin 6 (IL6), and tumor necrosis factor (INF-alpha) in the injured group were higher. However, paeoniflorin decreased these parameters, and TRPM8 and TRPV1 levels were restored to normal. From immunofluorescence experiments, the levels of TRPA1 and TRPV1 increased dramatically and, after treatments, the levels of TRPA1 and TRPV1 decreased. Therefore, paeoniflorin alleviated chronic neuralgia by decreasing inflammatory factors, suppressing p38 MAPK phosphorylation and reducing the expression of TRP proteins.

• 单位
  南方医科大学