Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey.
Pharmacol Biochem Behav. 2012 Aug;102(2):344-8. doi: 10.1016/j.pbb.2012.05.006. Epub 2012 May 17.
The role of 5-HT7 receptors in the nociceptive processing received most attention during the last few years. The involvement of 5-HT₇ receptors in nerve injury-induced neuropathic pain states have been reported only recently; however, there are no reports on its contribution in diabetic neuropathic pain. We therefore planned to investigate the effect of 5-HT₇ receptor activation on the changes of nociceptive threshold in diabetic mice. Diabetes was induced by a single intraperitoneal injection of streptozocin (150 mg/kg, i.p.). The nociceptive responses in normal and diabetic animals were tested in the hot-plate and tail-flick assays. Both hot-plate and tail-flick latencies significantly shortened at 1-3/4 weeks (thermal hyperalgesia) and prolonged at 6-7 weeks (thermal hypoalgesia) after streptozocin administration. At the dose of 10 mg/kg, systemic injections of AS-19, a selective 5-HT₇ receptor agonist, reduced thermal hyperalgesia at early stage of diabetes, but did not influence thermal hypoalgesia at late stage. Co-administration of SB-258719, a selective 5-HT₇ receptor antagonist, at a dose that had no effect on its own (10 mg/kg), reversed the anti-hyperalgesic effect of AS-19. Our results indicate that systemic administration of 5-HT₇ receptor agonists may have clinical utility in treating diabetic neuropathic pain.
在过去几年中，5-HT7 受体在痛觉处理中的作用受到了最多的关注。最近才报道了 5-HT7 受体参与神经损伤引起的神经性疼痛状态，但没有关于其在糖尿病性神经病理性疼痛中的作用的报道。因此，我们计划研究 5-HT7 受体激活对糖尿病小鼠痛觉阈值变化的影响。糖尿病通过单次腹腔注射链脲佐菌素（150mg/kg，ip）诱导。在热板和尾巴闪烁试验中测试正常和糖尿病动物的痛觉反应。在链脲佐菌素给药后 1-3/4 周（热痛觉过敏）和 6-7 周（热痛觉减退），热板和尾巴闪烁潜伏期明显缩短。在 10mg/kg 的剂量下，系统注射 AS-19，一种选择性 5-HT7 受体激动剂，可减轻糖尿病早期的热痛觉过敏，但对晚期的热痛觉减退无影响。在自身无作用剂量（10mg/kg）下，共给予 SB-258719，一种选择性 5-HT7 受体拮抗剂，可逆转 AS-19 的抗痛觉过敏作用。我们的结果表明，系统给予 5-HT7 受体激动剂可能在治疗糖尿病性神经病理性疼痛方面具有临床应用价值。
