Exploring the effects of TRPV۱ channel activation in the locus coeruleus on morphine-induced analgesia in rats with diabetic neuropathy using the hot-plate test

Introduction: Diabetic neuropathies (DN), a group of neuropathic disorders linked to diabetes mellitus, often manifest as peripheral neuropathy characterized by hyperalgesia and can affect all forms of diabetes. Morphine is known to inhibit the activity of locus coeruleus (LC) neurons, which play a crucial role in pain modulation. The TRPV۱ receptor, associated with capsaicin, is expressed in several brain nuclei involved in pain perception, including the LC nucleus. This study aims to investigate the influence of TRPV۱ in the LC on thermal hyperalgesia in both morphine-dependent and non-dependent rats suffering from DN. Methods: This study involved male Wistar rats, with diabetic neuropathy (DN) induced by administering streptozotocin (STZ) at a dose of ۶۰ mg/kg. Morphine sulfate, at a dosage of ۳ mg/kg, was administered intraperitoneally once daily for three consecutive days. Subsequently, we explored the activation of TRPV۱ channels using capsaicin, at a concentration of ۱۰ nmol, in mediating thermal hyperalgesia in both normal and neuropathic rats. Results: Our findings revealed that activation of TRPV۱ receptors in the LC significantly restored the decreased hot plate threshold in diabetic non-dependent rats. Conversely, this activation had no impact on diabetic-morphine-dependent rats. Conclusion: The findings of this study imply that targeting the capsaicinoid system may serve as an effective pharmacological strategy for treating patients with peripheral neuropathy.

کلیدواژه ها:

Diabetic neuropathy ، Thermal hyperalgesia ، Capsaicin ، Morphine ، Locus coeruleus ، Hot plate test