期刊
FRONTIERS IN NEUROSCIENCE
卷 14, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2020.00884
关键词
5-HT(6)receptors; neuropathic pain; mechanical allodynia; AC; PKA; anti-nociception; ventrolateral orbital cortex
资金
- National Natural Science Foundation of China [81971792, 81870886, 81901920]
- China Postdoctoral Science Foundation [2019M663746]
Mechanical allodynia, characterized by a painful sensation induced by innocuous stimuli, is thought to be caused by disruption in pain-related regions. Identification and reversal of this pathologic neuroadaptation are therefore beneficial for clinical treatment. Previous evidence suggests that 5-HT(6)receptors in the ventrolateral orbital cortex (VLO) are involved in neuropathic pain, but their function is poorly understood. The aim of the present study is to unveil the role of 5-HT(6)receptors in the VLO and the underlying mechanisms in pain modulation. Here, by using the spared nerve injury (SNI) pain model, first, we report that 5-HT(6)receptor protein decreased in the contralateral VLO compared with the ipsilateral VLO in rats with allodynia. Second, microinjection of the selective 5-HT(6)receptor agonists EMD-386088 and WAY-208466 into the contralateral VLO consistently and significantly depressed allodynia. Third, microinjection of the selective antagonist SB-258585 blocked the agonist-induced anti-allodynic effect, while the antagonist applied alone to the VLO had no effect. Furthermore, the anti-nociceptive effect of EMD-386088 on neuropathic pain was prevented by the adenylate cyclase (AC) inhibitor SQ-22536, and protein kinase A (PKA) inhibitor H89, suggesting that AC/PKA signaling might underlie the antinociception of agonists. Finally, the 5-HT(6)receptors were found to be colocalized with a glutamate transporter (EAAC1) by immunofluorescent staining, and the glutamate receptor antagonist kynurenic acid was found to completely block antinociception. These findings indicated that the antinociceptive effect of 5-HT(6)receptor agonists might occur via interaction with the glutamatergic system. Altogether, the agonists activated 5-HT(6)receptors present in the glutamatergic neurons in the VLO to facilitate the AC/PKA cascade, which subsequently might evoke glutamate release, thus depressing allodynia. These findings suggest a potential therapeutic role of 5-HT(6)receptor agonists in treating neuropathic pain.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据