Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2019 Jun;82(6):457-463. doi: 10.1097/JCMA.0000000000000115.
Although current neuropathic pain treatment guidelines do not recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), whether NSAIDs can serve as a useful adjuvant to conventional multimodal therapy remains unclear.
The spared nerve injury (SNI) rats rapidly developed profound and long-lasting spontaneous and evoked pain behaviors, including mechanical and cold allodynia of the ipsilateral hind paw. At day 5, we first characterized the nociceptive responses to ketorolac, tramadol, pregabalin, and their combinations.
We found that tramadol and pregabalin exerted dose-dependent analgesic effects on both spontaneous and evoked behaviors. However, ketorolac alone did not suppress any behaviors regardless of the dose. Ketorolac-tramadol and ketorolac-pregabalin produced variable degrees of additive suppression of spontaneous and evoked behavioral responses. Cold allodynia was profoundly diminished after ketorolac was added to ineffective pregabalin or tramadol. Mechanical allodynia was markedly attenuated by ketorolac-pregabalin but less so by ketorolac-tramadol mixtures.
Our data demonstrated that an NSAID alone failed to relieve spontaneous or evoked pain behaviors in the rat SNI model, but when combined with a weak opioid and α-2-δ-ligand produced a profound synergistic analgesic effect on cold allodynia and discrepant efficacy for mechanical allodynia and spontaneous pain.
尽管目前的神经病理性疼痛治疗指南不建议使用非甾体抗炎药（NSAIDs），但 NSAIDs 是否可以作为常规多模式治疗的有用辅助手段尚不清楚。
spared nerve injury (SNI) 大鼠迅速出现严重且持久的自发性和诱发性疼痛行为，包括同侧后足的机械性和冷感觉过敏。在第 5 天，我们首先对酮咯酸、曲马多、普瑞巴林及其组合对伤害性感受的反应进行了特征描述。
我们发现曲马多和普瑞巴林对自发性和诱发性行为均表现出剂量依赖性的镇痛作用。然而，酮咯酸单独使用时，无论剂量如何，均不能抑制任何行为。酮咯酸-曲马多和酮咯酸-普瑞巴林联合使用对自发性和诱发性行为反应均有不同程度的相加抑制作用。加用酮咯酸可显著减轻无效普瑞巴林或曲马多引起的冷感觉过敏。酮咯酸-普瑞巴林可显著减轻机械性痛觉过敏，但酮咯酸-曲马多混合物的效果较差。
我们的数据表明，单独使用 NSAIDs 不能缓解大鼠 SNI 模型中的自发性或诱发性疼痛行为，但与弱阿片类药物和 α-2-δ-配体联合使用时，对冷感觉过敏产生了显著的协同镇痛作用，而对机械性痛觉过敏和自发性疼痛的疗效则不同。
