Funded by Deanship of Scientific ResearchAmount: 14750 JD
Peripheral neuropathic pain is a significant medical problem. It is usually an under-treated secondary symptom of many diseases including diabetes mellitus and an adverse effect of many chemotherapeutic agents such as cisplatin. Chemotherapy-induced Peripheral Neuropathy (CIPN) may result from toxic insults, oxidative stress, apoptotic mechanisms, altered calcium homeostasis, mitochondrial toxicity, axon degeneration leading to disturbed axonal transport and membrane remodeling, in addition to the toxic effects on Schwann cells and the activation of the immune system and neuroinflammation. The anti-diabetic drug metformin is widely used to improve glycemic control in diabetes patients. There is a growing evidence that metformin enhances the efficacy of cancer treatment. Recent findings also showed that metformin reverses established mechanical allodynia in models of neuropathic pain induced by spinal nerve ligation in rats, and protects against CIPN in mice. Recent studies also demonstrated that oxaliplatin treated neurons showed a dose dependent enhancement of the response to TRPV1 agonists, this sensitization induced by oxaliplatin could be mediated by the increased intracellular cAMP levels leading to TRPV1 phosphorylation.
The aim of this study is to evaluate the protective role of metformin against chemotherapy-induced neuropathic pain and to investigate the molecular mechanisms that underlie metformin protective role in CIPN models specially its effect on TRPV1 function.