Broom D C, Samad T A, Kohno T, Tegeder I, Geisslinger G, Woolf C J
Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Neuroscience. 2004;124(4):891-900. doi: 10.1016/j.neuroscience.2004.01.003.
Cyclooxygenase-2 (COX-2) after induction peripherally, and within the CNS, plays an important role in producing inflammatory pain. However, its role in neuropathic pain models is controversial. Recently a robust and persistent model of partial nerve injury pain, the spared nerve injury (SNI) model, has been developed. The aim of the present study was to examine the regulation of COX-2 in the rat SNI model and to evaluate the effectiveness of the selective COX-2 inhibitor rofecoxib in preventing neuropathic allodynia and hyperalgesia. RNase protection assays revealed only a very small and transient increase in COX-2 mRNA in the dorsal horn of the spinal cord in the SNI model with a maximum change at 24 h. Immunohistochemical analysis showed a small increase in COX-2 protein in the deep layers of the dorsal horn 10 h following SNI surgery. Rofecoxib (100 microM) did not affect spontaneous excitatory postsynaptic currents or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propanoic acid (AMPA) and N-methyl-d-aspartate (NMDA) responses in lamina II neurons from spinal cords of animals with SNI indicating no detectable action on transmitter release or postsynaptic activity. Furthermore, rofecoxib treatment (1 and 3.2 mg/kg for 5 and 3 days respectively starting on the day of surgery) failed to modify the development of allodynia and hyperalgesia in the SNI model. However, rofecoxib significantly reduced inflammatory hypersensitivity evoked by injection of complete Freund's adjuvant into one hindpaw, indicating that the doses used were pharmacologically active. The pain hypersensitivity produced by the SNI model is not COX-2-dependent.
环氧化酶-2（COX-2）在外周诱导后以及在中枢神经系统内，在产生炎性疼痛中起重要作用。然而，其在神经性疼痛模型中的作用存在争议。最近，一种强大且持久的部分神经损伤疼痛模型—— spared nerve injury（SNI）模型已被开发出来。本研究的目的是检查大鼠SNI模型中COX-2的调节情况，并评估选择性COX-2抑制剂罗非昔布在预防神经性异常性疼痛和痛觉过敏方面的有效性。核糖核酸酶保护分析显示，在SNI模型中，脊髓背角COX-2 mRNA仅有非常小且短暂的增加，在24小时时变化最大。免疫组织化学分析表明，SNI手术后10小时，背角深层COX-2蛋白有小幅增加。罗非昔布（100 microM）对SNI动物脊髓II层神经元的自发兴奋性突触后电流或α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和N-甲基-D-天冬氨酸（NMDA）反应没有影响，表明对递质释放或突触后活动没有可检测到的作用。此外，罗非昔布治疗（分别在手术当天开始，以1和3.2 mg/kg的剂量给药5天和3天）未能改变SNI模型中异常性疼痛和痛觉过敏的发展。然而，罗非昔布显著降低了将完全弗氏佐剂注射到一只后爪所诱发的炎性超敏反应，表明所用剂量具有药理活性。SNI模型产生的疼痛超敏反应不依赖于COX-2。
