An investigation on melatonin administration in painful diabetic neuropathy: Contribution of cation channels and adrenergic related effects

Diabetic neuropathic pain is a highly complex syndrome whose radical treatment has not been discovered yet and it affects quality of life of the patient evidently. Melatonin is a promising drug in scope of this area with a wide spectrum of effects. In this study, the effects and mechanism of action of melatonin on diabetic neuropathic pain have been investigated through in vivo behavioral and in vitro electrophysiological experiments. In the STZ-induced diabetic model, subacute administration of 50 mg/kg, melatonin for 14 days reduced diabetes-induced hyperalgesia and allodynia responses comparable to the reference drug gabapentin by regulating locomotor activity using the Hargreave's and e-Von Frey tests, respectively. The antihyperalgesic and antiallodynic effects of melatonin were reversed with α1, α2 and β-adrenoceptor antagonist administrations findings pointed out that these effects were mediated by the participation of noradrenergic system. On the other hand, through in vitro analyzing effects of melatonin on parameters related to action potential, together with its effects on K+ currents, performed via patch clamp experiments, that exerts a reducing effect on neuronal activity and excitability via opening of K+ channels by increasing the amplitude of IA current, which is one of the systems that play a primary role in pain relief. In conclusion, melatonin shows its antihyperalgesic and antiallodynic effects by using the K+ channel and the noradrenergic system axis. Thus, melatonin provides a promising clinical approach of diabetic neuropathic pain with safety and efficiently.