Curcumin ameliorates oxaliplatin-induced allodynia response and melanocortin downregulation in the spinal cord

Abstract

Introduction: Oxaliplatin is a platinum-based chemotherapy agent that often causes chemotherapy-induced peripheral neuropathy (CIPN). This effect limits the potential activity and decreases the cancer patient’s quality of life. Melanocortin and transient receptor potential ankyrin 1 (TRPA1) pathways are believed to be essential in recruiting an allodynia response. Based on previous studies, curcumin has shown antioxidant and anti-inflammatory activities that could potentially be useful for decreasing the allodynia effects of oxaliplatin treatment. This study investigated the effect of curcumin on CIPN conditions. In addition, we further elaborated to measure the involvement of spinal melanocortin and the TRPA1 system. Materials and Methods: A total of 30 male Balb/C mice aged 6-7 weeks old and weighing 20-30 g were used in this study. Mice were injected with oxaliplatin 3 mg/kg four times in the first week of the study. In the second week of the study, curcumin 30, 60, and 120 mg/kg was injected intraperitoneally for 7 days. Allodynia response was measured using the von Frey filament test. Melanocortin 4 receptor (Mc4r), Pro-opiomelanocortin (Pomc) and Trpa1 mRNA expressions were measured using RT-qPCR. Results: Oxaliplatin-induced mechanical allodynia response in mice, characterized by a decrease in the 50% withdrawal threshold parameter, was followed by a significant decrease in the Mc4r, Pomc, and Trpa1 mRNA expressions in the spinal cord. Curcumin administration in all doses improves the 50% withdrawal threshold parameter in mice induced by oxaliplatin. Furthermore, curcumin increases the Mc4r and Pomc, but not the Trpa1 mRNA expressions in the spinal cord. Conclusion: Curcumin significantly reduces the allodynia response induced by oxaliplatin. In addition, curcumin ameliorates the melanocortin, but not TRPA1, downregulation in the spinal cord.