Sweitzer S M, Schubert P, DeLeo J A
Department of Pharmacology and Toxicology, Dartmouth College, Hanover, New Hampshire, USA.
J Pharmacol Exp Ther. 2001 Jun;297(3):1210-7.
The present study was undertaken to determine whether propentofylline, a glial modulating agent, could both prevent the induction of mechanical allodynia and attenuate existing mechanical allodynia in a rodent L5 spinal nerve transection model of neuropathic pain. In a preventative paradigm, propentofylline (1 and 10 mg/kg intraperitoneally) was administered systemically daily, beginning 1 day prior to nerve transection. This regimen produced a dose-dependent decrease in mechanical allodynia (p < 0.01). In another preventative paradigm, propentofylline (0.1, 1, or 10 microg) was administered daily intrathecally via direct lumbar puncture. Intrathecal administration of propentofylline was more effective than systemic administration at dose dependently reducing mechanical allodynia (p < 0.01). The effect of systemic propentofylline on existing allodynia was examined with 0.1-, 1-, and 10-mg/kg intraperitoneal administration initiated on day 4 post L5 spinal nerve transection. Systemic propentofylline was found to be equally effective in the attenuation of existing allodynia (p < 0.01) as in the prevention of allodynia in this rodent model of neuropathic pain. Spinal cords (L4-L6 segments) were removed for immunohistochemical analysis on day 10 or 20 post-transection. Microglial and astrocytic activation was decreased by both peripheral and central administration of propentofylline in both preventative and existing allodynia paradigms. This research supports a growing body of literature highlighting the importance of glial activation in the development of persistent neuropathic pain states, and the potential to therapeutically modulate glial activation in the treatment of neuropathic pain.
本研究旨在确定神经胶质调节药物丙戊茶碱是否既能预防机械性异常性疼痛的诱发，又能减轻啮齿动物L5脊髓神经横断性神经病理性疼痛模型中已有的机械性异常性疼痛。在预防性实验中，从神经横断前1天开始，每天腹腔注射丙戊茶碱（1和10毫克/千克）。该方案使机械性异常性疼痛呈剂量依赖性降低（p < 0.01）。在另一个预防性实验中，每天通过直接腰椎穿刺鞘内注射丙戊茶碱（0.1、1或10微克）。鞘内注射丙戊茶碱在剂量依赖性降低机械性异常性疼痛方面比全身给药更有效（p < 0.01）。在L5脊髓神经横断后第4天开始腹腔注射0.1、1和10毫克/千克丙戊茶碱，以研究全身应用丙戊茶碱对已有异常性疼痛的影响。发现在该啮齿动物神经病理性疼痛模型中，全身应用丙戊茶碱在减轻已有异常性疼痛方面（p < 0.01）与预防异常性疼痛同样有效。在横断后第10天或第20天取出脊髓（L4 - L6节段）进行免疫组织化学分析。在预防性和已有异常性疼痛的实验范式中，外周和中枢给予丙戊茶碱均能减少小胶质细胞和星形胶质细胞的激活。这项研究支持了越来越多的文献强调神经胶质细胞激活在持续性神经病理性疼痛状态发展中的重要性，以及在治疗神经病理性疼痛中通过治疗调节神经胶质细胞激活的潜力。
