Department of Veterinary Physiology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Department of Oral Physiology, School of Dentistry, Kyung Hee University, Seoul, Korea.
Br J Pharmacol. 2018 Feb;175(3):558-572. doi: 10.1111/bph.14109. Epub 2018 Jan 5.
Although we have recently demonstrated that spinal astrocyte gap junctions mediate the development of mirror-image pain (MIP), it is still unclear which astrocyte-derived factor is responsible for the development of MIP and how its production is controlled. In the present study, we focused on the role of ipsilateral versus contralateral D-serine in the development of MIP and investigated the possible involvement of σ1 receptors and gap junctions in astrocyte D-serine production.
Following carrageenan injection, mechanical allodynia was tested at various time points to examine the effect of individual drugs. Immunohistochemistry and Western blot analyses were performed to clarify the expression levels of spinal D-serine, serine racemase, σ1 receptors and connexin 43.
The expression of ipsilateral D-serine was up-regulated during the early phase of inflammation, while contralateral D-serine increased during the later phase of inflammation. The pharmacological inhibition of D-serine during the early phase blocked the development of both ipsilateral and contralateral mechanical allodynia. However, the inhibition of D-serine during the later phase of inflammation blocked contralateral, but not ipsilateral mechanical allodynia. Furthermore, the inhibition of σ1 receptors during the earlier phase of inflammation inhibited the increase in ipsilateral D-serine. Conversely, the blockade of astrocyte gap junctions suppressed the up-regulation of contralateral D-serine during the later phase of inflammation.
Spinal astrocyte D-serine plays an important role in the development of mirror-image pain. Furthermore, σ1 receptors and astrocyte gap junction signalling mediate ipsilateral and contralateral D-serine production respectively.
尽管我们最近已经证明脊髓星形胶质细胞缝隙连接介导镜像疼痛（MIP）的发展，但仍不清楚星形胶质细胞衍生的哪种因子负责 MIP 的发展，以及其产生如何受到控制。在本研究中，我们专注于同侧与对侧 D-丝氨酸在 MIP 发展中的作用，并研究了 σ1 受体和缝隙连接在星形胶质细胞 D-丝氨酸产生中的可能参与。
在角叉菜胶注射后，在不同时间点测试机械性痛觉过敏，以检查单独药物的作用。进行免疫组织化学和 Western blot 分析，以阐明脊髓 D-丝氨酸、丝氨酸消旋酶、σ1 受体和连接蛋白 43 的表达水平。
同侧 D-丝氨酸的表达在炎症早期上调，而对侧 D-丝氨酸在炎症后期增加。在炎症早期抑制 D-丝氨酸的药理学作用可阻断同侧和对侧机械性痛觉过敏的发展。然而，在炎症后期抑制 D-丝氨酸抑制了对侧机械性痛觉过敏，但不抑制同侧机械性痛觉过敏。此外，在炎症早期抑制 σ1 受体抑制了同侧 D-丝氨酸的增加。相反，在炎症后期阻断星形胶质细胞缝隙连接抑制了对侧 D-丝氨酸的上调。
脊髓星形胶质细胞 D-丝氨酸在镜像疼痛的发展中起重要作用。此外，σ1 受体和星形胶质细胞缝隙连接信号分别介导同侧和对侧 D-丝氨酸的产生。
