Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA.
Anesthesiology. 2010 May;112(5):1216-24. doi: 10.1097/ALN.0b013e3181d94d8b.
Nonsteroidal antiinflammatory drugs, the most commonly used analgesics, reduce pain not only by inhibiting cyclooxygenase at peripheral sites of inflammation but also by potentially inhibiting cyclooxygenase in the central nervous system, especially the spinal cord. Animal studies suggest that products of cyclooxygenase in the spinal cord do not alter pain responses to acute noxious stimuli but reduce pain and sensitization after peripheral inflammation. We used a spinal injection of small doses of the cyclooxygenase inhibitor ketorolac to survey the role of spinal cyclooxygenase in human experimental pain and hypersensitivity states.
After regulatory agency approval and informed consent, we examined the effect of 2.0 mg intrathecal ketorolac in 41 healthy volunteers to acute noxious thermal stimuli in normal skin and to mechanical stimuli in skin sensitized by topical capsaicin or ultraviolet burn. We also examined the effect of intravenous ketorolac.
Intrathecal ketorolac reduced hypersensitivity when it was induced by a combination of ultraviolet burn plus intermittent heat and, according to one of the two analytical strategies, when it was induced by ultraviolet burn alone.
These data suggest a more limited role for spinal cord cyclooxygenase in human pain states than predicted by studies in animals.
非甾体类抗炎药(NSAIDs)是最常用的镇痛药,不仅通过抑制炎症部位外周的环氧化酶来减轻疼痛,还可能通过抑制中枢神经系统(尤其是脊髓)中的环氧化酶来减轻疼痛。动物研究表明,脊髓中环氧化酶的产物不会改变对急性有害刺激的疼痛反应,但会减轻外周炎症后的疼痛和敏化。我们使用小剂量的脊髓注射环氧化酶抑制剂酮咯酸来调查脊髓中环氧化酶在人类实验性疼痛和过敏状态中的作用。
在监管机构批准和知情同意后,我们检查了 41 名健康志愿者鞘内给予 2.0mg 酮咯酸对正常皮肤急性有害热刺激和辣椒素或紫外线灼伤引起的皮肤敏化的机械刺激的影响。我们还检查了静脉内给予酮咯酸的影响。
鞘内给予酮咯酸可减轻由紫外线灼伤加间歇性热引起的过敏,根据两种分析策略之一,还可减轻由紫外线灼伤单独引起的过敏。
这些数据表明,脊髓中环氧化酶在人类疼痛状态中的作用比动物研究预测的要有限。