Microglial interleukin-1β in the ipsilateral dorsal horn inhibits the development of mirror-image contralateral mechanical allodynia through astrocyte activation in a rat model of inflammatory pain
Microglial interleukin-1β in the ipsilateral dorsal horn inhibits the development of mirror-image contralateral mechanical allodynia through astrocyte activation in a rat model of inflammatory pain
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DOI：
10.1097/j.pain.0000000000000148
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发表时间：
2015-06-01
期刊：
影响因子：
7.4
通讯作者：
Lee, Jang-Herh
中科院分区：
文献类型：
--
作者：
Choi, Hoon-Seong;Roh, Dae-Hyun;Lee, Jang-Herh
身体一侧的损伤也会导致对侧未受影响的一侧的疼痛，称为镜像疼痛（MIP）。目前，负责MIP发展的机制尚不清楚。在这项研究中，我们调查了参与脊髓小胶质细胞和白细胞介素-1 β（IL-1 β）在MIP的发展使用外周炎性疼痛模型。在单侧角叉菜胶注射后，评价两个后爪中的机械性异常性疼痛（MA）和脊髓lba-1、IL-1 β和GFAP的表达水平。注射角叉菜胶后3小时开始诱导同侧MA，而注射角叉菜胶后5天出现对侧MA延迟发作。单次鞘内注射（IT）在角叉菜胶注射当天注射米诺环素（一种选择性抑制小胶质细胞活化的四环素衍生物）或白细胞介素-1受体拮抗剂（IL-1 ra）可引起对侧MA的早期暂时诱导，而重复i.t.从第0天到第3天用这些药物治疗导致了持久的对侧MA，这在其晚期发展中是明显的。我们进一步表明IL-1 β定位于小胶质细胞，米诺环素抑制角叉菜胶诱导的脊髓lba-1和IL-1 β表达增加。相反，米诺环素或IL-1 ra预处理增加GFAP表达与对照组相比。然而，用氟柠檬酸（一种星形胶质细胞抑制剂）预处理可恢复米诺环素或IL-1 ra诱导的对侧MA。这些结果表明，脊髓IL-1 β来源于激活的小胶质细胞暂时抑制星形胶质细胞的激活，这可以最终防止在炎症条件下对侧MA的发展。这些结果表明，小胶质细胞IL-1 β在调节炎症MIP的诱导中起重要作用。
Damage on one side of the body can also result in pain on the contralateral unaffected side, called mirror-image pain (MIP). Currently, the mechanisms responsible for the development of MIP are unknown. In this study, we investigated the involvement of spinal microglia and interleukin-1 beta (IL-1 beta) in the development of MIP using a peripheral inflammatory pain model. After unilateral carrageenan injection, mechanical allodynia (MA) in both hind paws and the expression levels of spinal lba-1, IL-1 beta, and GFAP were evaluated. lpsilateral MA was induced beginning at 3 hours after carrageenan injection, whereas contralateral MA showed a delayed onset occurring 5 days after injection. A single intrathecal (it.) injection of minocycline, a tetracycline derivative that displays selective inhibition of microglial activation, or an interleukin-1 receptor antagonist (IL-1ra) on the day of carrageenan injection caused an early temporary induction of contralateral MA, whereas repeated i.t. treatment with these drugs from days 0 to 3 resulted in a long-lasting contralateral MA, which was evident in its advanced development. We further showed that IL-1 beta was localized to microglia and that minocycline inhibited the carrageenan-induced increases in spinal lba-1 and IL-1 beta expression. Conversely, minocycline or IL-1ra pretreatment increased GFAP expression as compared with that of control rats. However, it. pretreatment with fluorocitrate, an astrocyte inhibitor, restored minocycline- or IL-1ra-induced contralateral MA. These results suggest that spinal IL-1 beta derived from activated microglia temporarily suppresses astrocyte activation, which can ultimately prevent the development of contralateral MA under inflammatory conditions. These findings imply that microglial IL-1 beta plays an important role in regulating the induction of inflammatory MIP.