Possible involvement of activation of spinal glia with chronic pain

慢性疼痛可能与脊髓神经胶质细胞的激活有关

• 批准号: 17591613
• 负责人: OBATA Hideaki
• 金额: $ 2.3万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591613/
• 关键词: Spinal glia; Microglia; Astrocyte; Hyperalgesia; Allodynia; Postoperative pain; Neuropathic pain; 髄グリア; アストロ際と痛覚過敏

Experiments with post-operative painMale Sprague-Dawley rats (250g) were used in all experiments. An incision was made on the plantar aspect of the hind paw. Mechanical hypersensitivity was measured by determining the withdrawal threshold to von Frey filaments applied to the paw. Intraperitoneral administration of selective microglial inhibitor minocycline (50 mg/kg/day for 3 d) did not inhibit mechanical hypersensitivity. 0X42 expression in the spinal cord, however, suppressed 3d after minocycline injection. Intretherecal administration of p38MAPK inhibitor SB203580 (10 μg/day for 3d) also did not inhibit mechanical hypersensitivity. In the spinal cord, p-p38MAPK expressions were colocalized in 0X42 positive cells. This means p38MAPK is only expressed in microglia. In contrast, same paradigm injection with minocycline and SB203580 inhibited mechanical allodynia in rats with neuropathic pain induced by L5 spinal nerve transection (SNT). We concluded that microglia in the spinal cord does not have important role in the post-operative pain.Experiments with neuropathic pain All animals used in this study were male Sprague-Dawely rats (160-180g). We used L5 spinal nerve transection (SNT) model with the some modification of spinal nerve ligation model described by Kim and Chung (1992). Selective glia cell inhibitor propentofylline was infused trathecally for 7 days by an osmotic infusion pump (1 μ1/h, 7 day pump, ALZET, Cupertino, CA) initiated just after, 14 d after, or 60 days after SNT. Intrathecal infusion of propentofylline started just after SNT suppressed the development of allodynia dose-dependently (0.1, 1 and 10 μg/day). Other two paradigms did not inhibit existing allodynia. In the spinal cord, expression of astrocytes (GFAP) was always suppressed after propentofylline infusion. We concluded that astrocytes in the spinal cord play an important role in development of neuropathic pain.

术后疼痛实验均采用雄性Sprague-Dawley大鼠（250g）。在后爪的足底做了一个切口。机械超敏反应是通过测定施加于爪上的冯弗雷丝的戒断阈值来测量的。腹腔内给药选择性小胶质细胞抑制剂米诺环素（50 mg/kg/天，连续3天）没有抑制机械超敏反应。然而，脊髓中0X42的表达在米诺环素注射后3d被抑制。注射p38MAPK抑制剂SB203580 （10 μg/天，连续3天）也没有抑制机械超敏反应。在脊髓中，p-p38MAPK的表达在0X42阳性细胞中共定位。这意味着p38MAPK仅在小胶质细胞中表达。相比之下，同一模式注射二甲胺四环素和SB203580对L5脊神经横断（SNT）所致的神经性疼痛大鼠的机械异位性疼痛有抑制作用。我们的结论是脊髓小胶质细胞在术后疼痛中没有重要作用。本研究所用动物均为雄性Sprague-Dawely大鼠（160-180g）。我们采用L5脊神经横断（SNT）模型，对Kim和Chung（1992）描述的脊神经结扎模型进行了一些修改。选择性胶质细胞抑制剂丙烯茶碱通过渗透泵（1 μ1/h， 7天泵，ALZET, Cupertino， CA）在SNT后、14天后或60天后开始经气管输注7天。在SNT抑制异位性疼痛的发生后立即开始鞘内输注丙烯茶碱（0.1、1和10 μg/d）。另外两种模式对现有的异常性疼痛没有抑制作用。在脊髓中，丙烯茶碱输注后，星形胶质细胞（GFAP）的表达始终受到抑制。我们得出结论，脊髓中的星形胶质细胞在神经性疼痛的发展中起重要作用。

项目成果

Possiblξinvolvement of spinal noradrenergic mechanisms in the anti-allodyllic effbct of intrathecally administered 5-HT_2c receptor agonistsin the rats with peripheral nerve injury

脊髓去甲肾上腺素能机制可能参与鞘内注射5-HT_2c受体激动剂对周围神经损伤大鼠的抗异常作用

• 发表时间: 2007
• 期刊: Eur J pharmacol 567
• 作者: Akira Kawai;Yasuo Beppu;Hirokazu Nakauma;Fumihiko Nakatani;Osamu Sato;Akira Kawai;Akira Kawai;Minoru Sakuraba;川井 章;川井 章;川井 章;川井 章;Hideaki Obata;Hideaki Obata;Hideaki Obata;Hideaki Obata;Hideaki Obata;Hideaki Obata
• 通讯作者: Hideaki Obata

Antiallonic effect of glial cell inhibitor in rats with neuropathic pain

神经胶质细胞抑制剂对神经病理性疼痛大鼠的抗异位作用

• 发表时间: 2007
• 作者: Hideaki Obata;Shigeru Saito;Shiro Koizuka;Koichi Nishikawa;Fumio Goto.;小幡英章;Hideaki Obata;Hideaki Obata;小幡英章;小幡 英章;Hideaki Obata
• 通讯作者: Hideaki Obata

脊髄グリアの活性化はラット術後痛モデルの感覚過敏に関与している

脊髓胶质细胞激活参与大鼠术后疼痛模型的感觉过敏

• 发表时间: 2007
• 作者: Hideaki Obata;Shigeru Saito;Shiro Koizuka;Koichi Nishikawa;Fumio Goto.;小幡英章;Hideaki Obata;Hideaki Obata;小幡英章;小幡 英章;Hideaki Obata;小幡英章
• 通讯作者: 小幡英章

α2受容体をターゲットにした慢性疼痛の治療

通过靶向 α2 受体治疗慢性疼痛

• 发表时间: 2008
• 期刊: ペインクリニック 29巻2号
• 作者: 小幡英章;林田健一郎;中島邦枝;齋藤繁
• 通讯作者: 齋藤繁

Alpha2-receptors in the dorsal horn of the spinal cord

脊髓背角的 Alpha2 受体

• 发表时间: 2007
• 期刊: Kasseido
• 作者: Akira Kawai;Yasuo Beppu;Hirokazu Nakauma;Fumihiko Nakatani;Osamu Sato;Akira Kawai;Akira Kawai;Minoru Sakuraba;川井 章;川井 章;川井 章;川井 章;Hideaki Obata;Hideaki Obata;Hideaki Obata;Hideaki Obata;Hideaki Obata
• 通讯作者: Hideaki Obata