Preventing oxaliplatin-induced neuropathic pain: Using berberine to inhibit the activation of NF-κB and release of pro-inflammatory cytokines in dorsal root ganglions in rats.

Abstract

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a serious, undesirable effect of cancer treatment which is particularly difficult to prevent. Berberine and its derivatives have been reported to display robust antioxidant and analgesic effects in rat models of diabetic neuropathic pain and peripheral nerve injury. However, the analgesic role of berberine on oxaliplatin-induced CIPNP remains unknown. The present study aimed to explore the analgesic effect of berberine on CIPNP. Sprague Dawley rats were used to create the CIPNP animal model by oxaliplatin administration. Behavioral tests were performed by von Frey test, acetone drop test, hot plate test, and motor coordination. The protein expression levels of NF-κB p65 and phosphorylated p65 in dorsal root ganglions (DGRs) were detected by western blot analysis. Finally, TNF-α and IL-6 levels in DRGs were measured using specific ELISA kits. The results from the behavioral analysis demonstrated that a single injection of berberine ameliorated the mechanical and cold allodynia and thermal hyperalgesia in the model rats in a dose-dependent manner. Cumulative administration of berberine prevented the mechanical and cold allodynia and thermal hyperalgesia in the development of CIPNP induced by oxaliplatin. This prophylactic effect of berberine was associated with reduced phosphorylation of p65 and with decreased levels of pro-inflammatory cytokines IL-6 and TNF-α. The present study indicated that berberine may have a role in preventing the development of CIPNP and may serve as a therapeutic compound for the treatment of CIPNP.