Activation of orexin-A receptors in the periaqueductal gray increases pain tolerance in healthy and diabetic male rats

Introduction: Diabetic neuropathic pain is a common complication of diabetes. While previous research has shown that direct administration of the neuropeptide orexin-A into the brain can elicit analgesic effects, the specific central nervous system regions and mechanisms mediating these pain-relieving actions remain incompletely characterized. Methods: The current study used male Wistar rats to investigate the antinociceptive effects of administering orexin-A directly into the ventrolateral periaqueductal gray (vlPAG) region of the midbrain, assessed via the tail-flick test performed ۵ minutes post-injection. The experiments compared the effects of intra-vlPAG orexin-A administration in both healthy control and diabetic animal models. Results: In the control groups, the analgesic effects of intra-vlPAG orexin-A were found to be sustained over the ۱-hour observation period. Importantly, orexin-A elicited a rapid and potent analgesic response in the diabetic animal groups as well. Conclusion: Collectively, these findings suggest a key functional role for the vlPAG orexinergic system in modulating pain tolerance, with implications for the potential therapeutic targeting of this system in the management of debilitating neuropathic pain conditions like diabetic peripheral neuropathy.

کلیدواژه ها:

Pain ، Tail-flick test ، Orexin A receptor ، Ventrolateral periaqueductal gray ، Diabetic neuropathy