Background & Aims
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent dose-limiting side effect and a major cause of persistent pain in cancer patients with chemotherapy. Although many treatments have been developed currently, there is still no effective strategy for preventing CIPN. Previous studies revealed that vinpocetine, a phosphodiesterase 1 inhibitor, can reduce oxidative stress and inflammatory cytokines. However, the role of vinpocetine in CIPN remained unclear. In this study, we investigated the analgesic effect of vinpocetine treatment and related mechanisms in CIPN.
Methods
A mouse model of CIPN was established using paclitaxel (2 mg/kg, i.p.) administered on 4 alternate days. Vinpocetine treatment was applied for 7 days following the completion of paclitaxel injections. Mechanical allodynia, cold allodynia, and thermal hyperalgesia were assessed using the von Frey test, acetone test, and Hargreaves test, respectively. Western blot analysis was employed to examine mitochondrial biogenesis-related proteins and the oxidative stress status in the spinal cord. To validate mitochondrial function, levels of reactive oxygen species (ROS) were observed and analyzed in the dorsal horn of the spinal cord.
Results
Repetitive administration of vinpocetine indicated the ability to attenuate symptoms of CIPN. The expression of mitochondrial biogenesis-related proteins was restored following vinpocetine treatment, and there was a reduction in ROS production after vinpocetine administration.
Conclusions
These findings demonstrated the analgesic properties of vinpocetine in CIPN. This suggests that promoting mitochondrial biogenesis through vinpocetine could be a novel therapeutic target for CIPN treatment by reducing oxidative stress.
References
[1] Agnes, J. P., V. W. D. Santos, R. N. das Neves, R. M. Gonçalves, M. Delgobo, C. S. Girardi, D. D. Lückemeyer, M. A. Ferreira, S. J. Macedo-Júnior, S. C. Lopes, F. Spiller, D. P. Gelain, J. C. F. Moreira, R. D. Prediger, J. Ferreira, and A. Zanotto-Filho. 2021. ‘Antioxidants Improve Oxaliplatin-Induced Peripheral Neuropathy in Tumor-Bearing Mice Model: Role of Spinal Cord Oxidative Stress and Inflammation’, J Pain, 22: 996-1013.
[2] Bagri, K., and R. Deshmukh. 2022. ‘Vinpocetine restores cognitive and motor functions in Traumatic brain injury challenged rats’, Inflammopharmacology, 30: 2243-59.
[3] Boyette-Davis, J. A., E. T. Walters, and P. M. Dougherty. 2015. ‘Mechanisms involved in the development of chemotherapy-induced neuropathy’, Pain Manag, 5: 285-96.
[4] Chung, J. M. 2004. ‘The role of reactive oxygen species (ROS) in persistent pain’, Mol Interv, 4: 248-50.
[5] Canta, A., E. Pozzi, and V. A. Carozzi. 2015. ‘Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)’, Toxics, 3: 198-223.
[6] Desforges, A. D., C. M. Hebert, A. L. Spence, B. Reid, H. A. Dhaibar, D. Cruz-Topete, E. M. Cornett, A. D. Kaye, I. Urits, and O. Viswanath. 2022. ‘Treatment and diagnosis of chemotherapy-induced peripheral neuropathy: An update’, Biomed Pharmacother, 147: 112671.
[7] Horvath, B., Z. Marton, R. Halmosi, T. Alexy, L. Szapary, J. Vekasi, Z. Biro, T. Habon, G. Kesmarky, and K. Toth. 2002. ‘In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine’, Clin Neuropharmacol, 25: 37-42.
[8] Luhach, K., G. T. Kulkarni, V. P. Singh, and B. Sharma. 2021. ‘Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress’, Autism Res, 14: 2270-86.