Huangqi Guizhi Wuwu Decoction Can Prevent and Treat Oxaliplatin Induced Neuropathic Pain by TNFα/IL-1β/IL-6/MAPK/NF-kB Pathway

Abstract Background: The mechanism of Huangqi Guizhi Wuwu Decoction in the prevention and treatment of oxaliplatin-induced neuropathic pain was unclear. Therefore, we explored the effect and mechanism of Huangqi Guizhi Wuwu Decoction in chemotherapy-induced neuropathic pain (CINP). Methods: Bodyweight and related behavioral testing of the rat model were utilized to explore the effect of Huangqi Guizhi Wuwu Decoction in CINP. ELISA was used to detect the levels of TNF-α, IL-1β, IL-6 inflammatory factors in the serum of chronic CINP rats induced by oxaliplatin. Immunohistochemistry and western blot analysis were applied to detect the expression of MAPK pathway related-proteins ERK1/2, p38, JNK, and the expression of downstream essential proteins c-Fos, CREB, and NF-κB. Results: By bodyweight and related behavioral testing of the rat model, we found that Huangqi Guizhi Wuwu Decoction can improve the slow weight gain of oxaliplatin-induced chronic CINP model rats, effectively prevent and treat oxaliplatin-induced regular CIPN rat model of hyperalgesia, and oppress the mechanical pain threshold, cold pain threshold, and heat pain threshold decreased. By ELISA, immunohistochemistry, and western blot analysis, we found that Huangqi Guizhi Wuwu Decoction can down-regulate the levels of TNF-α, IL-1β, IL-6 inflammatory factors in the serum of chronic CINP rats induced by oxaliplatin, then suppressed the expression of MAPK pathway related-proteins ERK1/2, p38 and JNK. After that, the expression of downstream essential proteins c-Fos, CREB, and Nf-κB also decreased. Conclusion: In conclusion, we found that Huangqi Guizhi Wuwu Decoction can combat nerve cell injury, reduce pain sensitization, and prevent and repair the damage of nerve cells in oxaliplatin CINP model rats by TNFα/IL-1β/IL-6/MAPK/NF-kB pathway.