Deleo T A, Hashizume H, Rutkowski M D, Weinstein T N
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0001, USA.
J Orthop Res. 2000 Nov;18(6):977-82. doi: 10.1002/jor.1100180618.
Low back pain is a common problem, affecting approximately two-thirds of the adult population. Of these individuals, a significant percentage will exhibit symptoms of radicular pain or sciatica. The purpose of this study was to determine the effect of one systemic (2 mg/kg) or intrathecal (0.2 mg/kg) dose of a selective cyclooxygenase-2 inhibitor (SC-236) in decreasing existing mechanical allodynia in a rat model of radiculopathy. Gait disturbance and mechanical allodynia (increased response to non-noxious von Frey monofilament stimuli) were assessed daily until the rats were killed 7 days after surgery. Robust mechanical allodynia developed in the rats in all groups except for those in the sham group by day 1 after surgery. Mechanical allodynia was significantly lower in the rats that received the systemic or the intrathecal dose of SC-236 than in those in the vehicle control group (analysis of variance followed by Bonferroni multiple comparison test, p = 0.002). The intrathecal drug route of administration produced greater attenuation in allodynia than the systemic dose, supporting a central mechanism of action of the cyclooxygenase-2 inhibitor (p = 0.002). The hypothesis that cyclooxygenase-2 is involved in spinal nociceptive processing after a nerve root injury was supported by this study. In addition, these data support continued basic science research to further elucidate central inflammatory processes that follow nerve root injury.
下背痛是一个常见问题,影响着约三分之二的成年人群。在这些个体中,相当大比例的人会出现神经根性疼痛或坐骨神经痛的症状。本研究的目的是确定一剂全身(2毫克/千克)或鞘内(0.2毫克/千克)剂量的选择性环氧化酶-2抑制剂(SC-236)在减轻神经根病大鼠模型中现有的机械性异常性疼痛方面的效果。每天评估步态障碍和机械性异常性疼痛(对无害的von Frey单丝刺激的反应增加),直至大鼠在手术后7天处死。除假手术组外,所有组的大鼠在手术后第1天均出现强烈的机械性异常性疼痛。接受全身或鞘内剂量SC-236的大鼠的机械性异常性疼痛明显低于载体对照组(方差分析后进行Bonferroni多重比较检验,p = 0.002)。鞘内给药途径比全身剂量在减轻异常性疼痛方面产生更大的作用,支持环氧化酶-2抑制剂的中枢作用机制(p = 0.002)。本研究支持环氧化酶-2参与神经根损伤后脊髓伤害性处理的假说。此外,这些数据支持继续进行基础科学研究,以进一步阐明神经根损伤后随之而来的中枢炎症过程。