Zhu Xiaoying, Conklin Dawn R, Eisenach James C
Program of Neuroscience, Department of Anesthesiology and Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Anesth Analg. 2005 May;100(5):1390-1393. doi: 10.1213/01.ANE.0000148127.53832.8E.
Intrathecal administration of cyclooxygenase (COX)-1, but not COX-2, specific inhibitors given on postoperative day 1 has analgesic effects in an incisional model of postoperative pain. We investigated the effects of preoperative administration of intrathecal COX inhibitors in this model. Fifteen minutes before surgery, rats received intrathecally the COX-1 preferring inhibitor, ketorolac, the specific COX-1 inhibitor, SC-560, the COX-2 inhibitor, NS-398, or vehicle. A 1-cm longitudinal incision was then made through skin, fascia, and muscles of the plantar aspect of a left paw in male rats. Withdrawal threshold to von Frey filaments was measured at 2 h, 4 h, and at intervals up to 5 days later. Ketorolac and SC-560 increased withdrawal threshold to mechanical stimulation, but NS-398 had no significant effect. These results suggest that COX-1 plays an important role in spinal cord pain processing and sensitization after surgery and that preoperative intrathecal administration of specific COX-1 inhibitors may be useful to treat postoperative pain.
在术后疼痛的切口模型中,于术后第1天鞘内注射环氧化酶(COX)-1而非COX-2特异性抑制剂具有镇痛作用。我们在该模型中研究了术前鞘内注射COX抑制剂的效果。手术前15分钟,大鼠鞘内注射COX-1选择性抑制剂酮咯酸、特异性COX-1抑制剂SC-560、COX-2抑制剂NS-398或赋形剂。然后在雄性大鼠左爪足底的皮肤、筋膜和肌肉上做一个1厘米长的纵向切口。在术后2小时、4小时以及直至5天后的不同时间间隔测量对von Frey细丝的撤针阈值。酮咯酸和SC-560提高了对机械刺激的撤针阈值,但NS-398没有显著作用。这些结果表明,COX-1在术后脊髓疼痛处理和敏化过程中起重要作用,术前鞘内注射特异性COX-1抑制剂可能有助于治疗术后疼痛。