Possible involvement of activation of spinal glia with chronic pain

在所有实验中使用雄性Sprague-Dawley大鼠（250 g）。在后爪的足底面上做一个切口。通过测定对应用于爪的von Frey细丝的撤回阈值来测量机械超敏反应。腹腔注射选择性小胶质细胞抑制剂米诺环素（50 mg/kg/天，持续3 d）不能抑制机械超敏反应。然而，在注射米诺环素后3d，脊髓中的0X 42表达受到抑制。p38 MAPK抑制剂SB 203580（10 μg/d，连续3d）的腹腔给药也不能抑制机械性超敏反应。在脊髓中，p-p38 MAPK表达共定位于0X 42阳性细胞。这意味着p38 MAPK仅在小胶质细胞中表达。与此相反，同样的范式注射米诺环素和SB 203580抑制机械异常性疼痛大鼠L5脊神经横断（SNT）诱导的神经病理性疼痛。神经病理性疼痛的实验本研究中使用的所有动物均为雄性Sprague-Dawely大鼠（160- 180 g）。我们使用了L5脊神经横断（SNT）模型，并对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戊茶碱在SNT后即刻、14 d或60 d开始通过渗透输注泵（1 μ l/h，7天泵，ALZET，库比蒂诺，CA）经鞘内输注7天。在SNT剂量依赖性地抑制异常性疼痛的发展后立即开始鞘内输注丙戊茶碱（0.1、1和10 μg/天）。其他两个范例没有抑制现有的异常性疼痛。在脊髓中，星形胶质细胞（GFAP）的表达总是受到抑制后propentofylline输注。我们的结论是，星形胶质细胞在脊髓神经病理性疼痛的发展中发挥了重要作用。

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.