Department of Anatomy, Shandong University School of Medicine, Jinan 250012, China.
Eur J Pharmacol. 2012 Apr 5;680(1-3):28-33. doi: 10.1016/j.ejphar.2012.01.011. Epub 2012 Jan 26.
Diabetic neuropathy is a common complication associated with diabetes and is frequently painful. However, mechanisms responsible for diabetic neuropathic pain are still unclear. Experimental evidence has shown that the galanin and its receptor are involved in pain sensitization. The objective of the present study was to investigate the role of galanin and its receptor antagonist or agonist on neuropathic pain in streptozotocin-induced diabetic rats. The expression of galanin, galanin receptors 1 and 2 in dorsal root ganglion (DRG) and spinal dorsal horn (SDH) in diabetic rats were detected by Western blot assay. The effects of galanin, galanin receptor antagonist M35, galanin receptor 1 agonist M617, and galanin receptor 2 agonist AR-M1896 on neuropathic pain were evaluated by mechanical stimuli. The results showed that (1) the diabetic rats showed a significant mechanical hyperalgesia between 4 and 12weeks; (2) galanin receptor 1 expression decreased in SDH in diabetic rats; (3) galanin receptor 2 expression decreased in DRG and SDH in diabetic rats; (4) intrathecal administration of exogenous galanin attenuated diabetic neuropathic pain, this effect could be blocked by pre-treatment with galanin receptor antagonist M35; and (5) intrathecal administration of galanin receptor 1 agonist M617, but not galanin receptor 2 agonist AR-M1896, attenuated diabetic neuropathic pain. These results imply that galanin acts through receptor 1, but not galanin receptor 2, to exert analgesic effect in diabetic neuropathic pain and is one of the potential therapeutic targets on diabetic neuropathic pain sensitization.
糖尿病性神经病变是一种常见的糖尿病相关并发症，常伴有疼痛。然而，导致糖尿病性神经病理性疼痛的机制尚不清楚。实验证据表明甘丙肽及其受体参与痛觉敏化。本研究旨在探讨甘丙肽及其受体拮抗剂或激动剂在链脲佐菌素诱导的糖尿病大鼠神经病理性疼痛中的作用。通过 Western blot 检测糖尿病大鼠背根神经节（DRG）和脊髓背角（SDH）中甘丙肽、甘丙肽受体 1 和 2 的表达。通过机械刺激评估甘丙肽、甘丙肽受体拮抗剂 M35、甘丙肽受体 1 激动剂 M617 和甘丙肽受体 2 激动剂 AR-M1896 对神经病理性疼痛的影响。结果表明：（1）糖尿病大鼠在 4 至 12 周时表现出明显的机械性痛觉过敏；（2）糖尿病大鼠 SDH 中甘丙肽受体 1 表达减少；（3）糖尿病大鼠 DRG 和 SDH 中甘丙肽受体 2 表达减少；（4）鞘内给予外源性甘丙肽可减轻糖尿病性神经病理性疼痛，该作用可被甘丙肽受体拮抗剂 M35 预处理阻断；（5）鞘内给予甘丙肽受体 1 激动剂 M617 而非甘丙肽受体 2 激动剂 AR-M1896 可减轻糖尿病性神经病理性疼痛。这些结果表明，甘丙肽通过受体 1 而不是甘丙肽受体 2 发挥镇痛作用，在糖尿病性神经病理性疼痛中发挥作用，是糖尿病性神经病理性疼痛敏化的潜在治疗靶点之一。
