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鞘内给予 α1 肾上腺素能拮抗剂酚妥拉明上调脊髓 GLT-1 并改善 SNI 模型大鼠镜像疼痛。

Intrathecal Administration of the α1 Adrenergic Antagonist Phentolamine Upregulates Spinal GLT-1 and Improves Mirror Image Pain in SNI Model Rats.

机构信息

Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.

Kinoshita Pain Clinic.

出版信息

Acta Med Okayama. 2022 Jun;76(3):255-263. doi: 10.18926/AMO/63719.

DOI:10.18926/AMO/63719
PMID:35790355
Abstract

Mirror image pain (MIP) is a type of extraterritorial pain that results in contralateral pain or allodynia. Glutamate transporter-1 (GLT-1) is expressed in astrocytes and plays a role in maintaining low glutamate levels in the synaptic cleft. Previous studies have shown that GLT-1 dysfunction induces neuropathic pain. Our previous study revealed bilateral GLT-1 downregulation in the spinal cord of a spared nerve injury (SNI) rat. We hypothesized that spinal GLT-1 is involved in the mechanism of MIP. We also previously demonstrated noradrenergic GLT-1 regulation. Therefore, this study aimed to investigate the effect of an α1 adrenergic antagonist on the development of MIP. Rats were subjected to SNI. Changes in pain behavior and GLT-1 protein levels in the SNI rat spinal cords were then examined by intrathecal administration of the α1 adrenergic antagonist phentolamine, followed by von Frey test and western blotting. SNI resulted in the development of MIP and bilateral downregulation of GLT-1 protein in the rat spinal cord. Intrathecal phentolamine increased contralateral GLT-1 protein levels and partially ameliorated the 50% paw withdrawal threshold in the contralateral hind paw. Spinal GLT-1 upregulation by intrathecal phentolamine ameliorates MIP. GLT-1 plays a role in the development of MIPs.

摘要

镜像疼痛(MIP)是一种躯体感觉异常性疼痛,表现为对侧疼痛或痛觉过敏。谷氨酸转运体-1(GLT-1)在星形胶质细胞中表达,在维持突触间隙中低水平谷氨酸方面发挥作用。先前的研究表明 GLT-1 功能障碍会引起神经性疼痛。我们之前的研究表明,在 spared nerve injury(SNI)大鼠的脊髓中双侧 GLT-1 下调。我们假设脊髓 GLT-1 参与 MIP 的发病机制。我们之前还证明了去甲肾上腺素能 GLT-1 的调节作用。因此,本研究旨在探讨α1 肾上腺素能拮抗剂对 MIP 发展的影响。大鼠接受 SNI 手术。通过鞘内给予 α1 肾上腺素能拮抗剂苯肾上腺素,然后进行 von Frey 测试和 Western blot 检测,观察 SNI 大鼠脊髓中疼痛行为和 GLT-1 蛋白水平的变化。SNI 导致 MIP 的发生和大鼠脊髓中 GLT-1 蛋白的双侧下调。鞘内苯肾上腺素增加了对侧 GLT-1 蛋白水平,并部分改善了对侧后爪的 50%足底撤回阈值。鞘内苯肾上腺素引起的脊髓 GLT-1 上调可改善 MIP。GLT-1 在 MIP 的发展中起作用。

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