Duan Hao, Zhang Ying, Zhang Xiao-Min, Xu Huan-Huan, Shu Jun, Xu Shi-Lian
Department of Physiology, School of Basic Medicine, Kunming Medical University, Chenggong, Kunming, Yunnan, People's Republic of China.
Department of Orthopedics, Second Affiliated Hospital, Kunming Medical University, Xishan, Kunming, Yunnan, People's Republic of China.
J Neurosci Res. 2015 Oct;93(10):1542-51. doi: 10.1002/jnr.23611. Epub 2015 Jun 24.
It has been reported that galanin and its receptors might be involved in the modulation and transmission of nociception in the central nervous system. Our previous research has also demonstrated that galanin induces antinociception in the nucleus accumbens (NAc) of intact rats. However, the interaction between galanin and its receptors in the NAc and the underlying mechanism of suppressing pain transmission remain unclear. The present study seeks to determine the antinociception induced by galanin receptor (GalR)-1 stimulation in the NAc of rats with neuropathic pain. The left sciatic nerve of rats was ligated to mimic a neuropathic pain model. Western blots showed that the expression of GalR1 was significantly upregulated in the NAc of rats with neuropathic pain. Intra-NAc injection of GalR1 agonist M617 induced a dose-dependent increase in hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulations in rats with neuropathic pain. Also, the effect of M617 was attenuated by M35, a GalR1/2 antagonist; at the same time, M35 reduced the galanin-induced antinociception, suggesting that GalR1 mediates antinociception induced by galanin in the NAc of rats with neuropathic pain. Furthermore, we found that M617-induced antinociception in rats with neuropathic pain was stronger than the antinociception in intact rats. We also found that injections of M617 and galanin each induced significant increases in HWL, but the galanin-induced antinociception was stronger than that of M617. All these results suggest that GalR1 plays an important role in antinociception and that other GalRs also are involved in pain modulation induced by galanin in the NAc of rats with neuropathic pain.
据报道，甘丙肽及其受体可能参与中枢神经系统中伤害性感受的调节和传递。我们之前的研究也表明，甘丙肽在完整大鼠的伏隔核（NAc）中诱导抗伤害感受。然而，NAc中甘丙肽与其受体之间的相互作用以及抑制疼痛传递的潜在机制仍不清楚。本研究旨在确定甘丙肽受体（GalR）-1刺激在神经性疼痛大鼠的NAc中诱导的抗伤害感受。结扎大鼠左侧坐骨神经以模拟神经性疼痛模型。蛋白质免疫印迹显示，神经性疼痛大鼠的NAc中GalR1的表达显著上调。向NAc内注射GalR1激动剂M617可使神经性疼痛大鼠对有害热刺激和机械刺激的后爪缩足潜伏期（HWL）呈剂量依赖性增加。此外，GalR1/2拮抗剂M35可减弱M617的作用；同时，M35可降低甘丙肽诱导的抗伤害感受，这表明GalR1介导了甘丙肽在神经性疼痛大鼠的NAc中诱导的抗伤害感受。此外，我们发现M617在神经性疼痛大鼠中诱导的抗伤害感受比在完整大鼠中更强。我们还发现，注射M617和甘丙肽均可使HWL显著增加，但甘丙肽诱导的抗伤害感受比M617更强。所有这些结果表明，GalR1在抗伤害感受中起重要作用，并且其他GalR也参与了甘丙肽在神经性疼痛大鼠的NAc中诱导的疼痛调节。
