脊髓水平环氧合酶-1在术后疼痛大鼠痛觉超敏中的作用(英文)

EFFECTS OF SPINAL CYCLOOXYGENASE-1(COX-1) ON MECHANICAL ALLODYNIA INDUCED BY POSTOPERATIVE PAIN IN RAT

为研究脊髓水平环氧合酶(COX)-1在术后疼痛形成和维持中的作用,运用免疫组化和免疫蛋白印记法观察切口痛模型大鼠腰段脊髓中COX-1蛋白在术前和术后2h,4h,6h,12h、1d、2d,3d、5d和7d的表达。通过测定机械刺激引起的缩足反射阈值(PWT)分别在术前、术后2h、1d、2d、3d、5d和7d观察术后痛觉超敏情况,并通过术后即刻或术后2h,24h鞘内给予非选择性COX抑制剂(ketorolac)、选择性COX-1抑制剂(SC-560)和选择性COX-2抑制剂(NS-398)观察其镇痛作用。结果表明:术后COX-1免疫反应阳性细胞主要集中在脊髓背角浅层,COX-1蛋白表达增加,4h达高峰,并且持续增加至12h。术后鞘内给予SC-560和ketorolac均能明显减轻皮肤切开诱发的机械性痛觉超敏,然而NS-398却无任何镇痛作用。本研究表明脊髓COX-1参与术后痛觉超敏的形成和维持的过程,鞘内给予COX-1抑制剂具有抗切口痛大鼠痛觉超敏的作用。

To identify the role of spinal cyclooxygenase （COX） -1 in the development and maintenance of postoperative pain, we examined the changes of COX-1 protein expression in lumbar spinal cord by immunohistochemistry and Western blot technique in rat plantar incision model at different time points （ pre-incision or 2 h, 4 h, 6 h, 12 h, 1 d, 2 d, 3 d, 5 d and 7 d after incision）. We also studied the antiallodynic effects of the COX inhibitors by intrathecal administration of non-selective COX inhibitors （ ketorolac ）, selective COX-1 （ SC- 560） or COX-2 inhibitor （NS-398） immediately or 2 h, 24 b after incision. The mechanical allodynia was evaluated by using paw withdrawal threshold （PWT） response to mechanical stimulation on pre-incision, 2 h, 1 d, 2 d, 3 d, 5 d and 7 d after incision or 30 min after drug treatment. The result showed that COX-1 immunoreactive cells mainly focused in the superficial laminae of lumbar spinal dorsal horn and expression of spinal COX-1 protein increased after incision, peaked at 4 h （P 〈 0.01 ） and lasted for 12 h. Postoperative treatment with both SC-560 and ketorolac significantly alleviating the mechanical allodynia induced by skin incision, but NS-398 had no such effect. This study demonstrates that spinal COX-1 involves in the development and maintenance of postoperative hypersensitivity and intrathecal COX-1 inhibitor has anti-allodynic effect on incision pain in the rat.