Possible involvement of activation of spinal glia with chronic pain

所有实验均采用雄性SD大鼠(250g)术后疼痛实验。在后爪的足底切开一道口子。通过测定对应用于爪子的von Frey细丝的退出阈值来测量机械超敏反应。选择性小胶质细胞抑制剂米诺环素(50 mg/kg/d，连用3d)不能抑制机械超敏反应。然而，注射米诺环素3d后，0X42在脊髓中的表达受到抑制。鞘内注射p38MAPK抑制剂SB203580(10μg/d，连用3d)也不能抑制机械超敏反应。在脊髓中，p-p38MAPK的表达主要分布在0X42阳性细胞中。这意味着p38MAPK只在小胶质细胞中表达。相反，注射米诺环素和SB203580可抑制L5脊神经切断(SNT)所致神经病理性疼痛大鼠的机械性痛觉过敏。我们的结论是，脊髓中的小胶质细胞在术后疼痛中没有重要作用。神经病理性疼痛实验本研究中使用的所有动物都是雄性SD大鼠(160-180克)。我们采用L5脊神经横断术(SNT)模型，对Kim和Chung(1992)描述的脊神经结扎模型进行了一些改进。分别于SNT后即刻、14d或60d开始用渗透压泵(1μ1/h，7d泵，ALZET，库比蒂诺，CA)经输注选择性胶质细胞抑制剂Proentofylline 7d。鞘内注射普罗普茶碱后，SNT剂量依赖地(0.1、1和10μg/d)抑制了痛觉过敏的发展。另外两种治疗模式并不能抑制现有的痛觉异常。在脊髓，注射丙戊茶碱后，星形胶质细胞(GFAP)的表达总是受到抑制。我们得出结论，脊髓中的星形胶质细胞在神经病理性疼痛的发生中起着重要作用。

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.