Therapeutic potential of melatonin in management of diabetic mellitus and diabetic neuropathic pain: Underlying mechanisms, challenges and future perspectives

Diabetes mellitus (DM), a global health issue, is a chronic metabolic disorder that mainly involves glucose homeostasis. It causes different complications, in particular, diabetic neuropathic pain (DNP). Pathophysiology of DM and DNP involves mitochondrial dysfunction, inflammation and oxidative stress. Melatonin is a neurohormone which is mainly released by the pineal gland and demonstrates neuroprotective, anti-inflammatory and antioxidant potentials. Reports indicate the role of melatonin in the modulation of insulin sensitivity and secretion thereby regulating glucose metabolism. Melatonin has also been shown to reduce neuropathic pain by influencing neurodegeneration, inflammation and oxidative stress. This review aims to explore different mechanisms through which melatonin affects DM and DNP so that its potential to be used as a therapeutic agent can be deciphered. Different preclinical and clinical evidence relating to the efficacy of melatonin will be analyzed in this review together with the limitations of using melatonin. The review will also propose some directions for applying these findings to clinical practice. Considering the multidimensional potential of melatonin and its safety, it can be used as a tool to develop therapeutic interventions for the management of DM and DNP.