Antinociceptive roles of galanin receptor 1 in nucleus accumbens of rats in a model of neuropathic pain

Antinociceptive roles of galanin receptor 1 in nucleus accumbens of rats in a model of neuropathic pain
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神经性疼痛模型中大鼠伏核甘丙肽受体 1 的镇痛作用

DOI:
10.1002/jnr.23611
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发表时间:
2015-10-01
影响因子:
4.2
通讯作者:
Xu, Shi-Lian
Xu, Shi-Lian
中科院分区:
医学3区
文献类型:
--
作者:
Duan, Hao;Zhang, Ying;Xu, Shi-Lian

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有报道称甘丙肽及其受体可能参与中枢神经系统痛觉的调节和传递。我们之前的研究也证明了甘丙肽在完整大鼠伏隔核(NAc)中具有抗痛觉作用。然而,甘丙肽及其受体在NAc中的相互作用及其抑制疼痛传递的潜在机制尚不清楚。本研究旨在确定丙氨酸受体(GalR)−1刺激对神经性疼痛大鼠NAc的抗痛觉作用。结扎大鼠左侧坐骨神经,模拟神经性疼痛模型。Western blot结果显示,神经性疼痛大鼠NAc中GalR1的表达明显上调。NAc内注射GalR1激动剂M617可诱导神经性疼痛大鼠对有害热刺激和机械刺激的后爪戒断潜伏期(HWL)的剂量依赖性增加。此外,GalR1/2拮抗剂M35可以减弱M617的作用;同时,M35降低了甘丙肽诱导的抗伤感受,提示GalR1介导了甘丙肽在神经性疼痛大鼠NAc中的抗伤感受作用。此外,我们发现M617诱导的神经性疼痛大鼠的抗疼痛感觉强于正常大鼠的抗疼痛感觉。我们还发现,注射M617和甘丙肽均可诱导HWL显著增加,但甘丙肽诱导的抗伤作用强于M617。上述结果提示GalR1在神经性疼痛大鼠NAc中具有重要的抗痛觉作用,其他galr也参与了丙氨酸诱导的疼痛调节。©2015 Wiley期刊公司
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. © 2015 Wiley Periodicals, Inc.