University of Oslo, Oslo, Norway Department of Anaesthesia - Ullevaal, Oslo University Hospital, Oslo, Norway Department of Anaesthesia, University of Heidelberg, Mannheim, Germany Department of Anaesthesia, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
Pain. 2011 Jun;152(6):1289-1297. doi: 10.1016/j.pain.2011.02.007. Epub 2011 Mar 10.
Opioids may enhance pain sensitivity resulting in opioid-induced hyperalgesia (OIH). Activation of spinal cyclooxygenase may play a role in the development of OIH. The aim of this study was to demonstrate remifentanil-induced postinfusion hyperalgesia in an electrical pain and a cold pain model, and to investigate whether COX-2 (parecoxib) or COX-1 (ketorolac) inhibition could prevent hyperalgesia after remifentanil infusion. Sixteen healthy males were enrolled in this randomized, double-blind, placebo-controlled crossover study. Each subject went through 4 sessions: control, remifentanil, parecoxib+remifentanil, and ketorolac+remifentanil. Transcutaneous electrical stimulation induced acute pain and areas of pinprick hyperalgesia. The areas of pinprick hyperalgesia were assessed before, during, and after a 30-minute infusion of either remifentanil or saline. The cold-pressor test (CPT) was performed before, at the end of, and 1 hour after the infusions. The subjects received a bolus of either saline, 40 mg parecoxib, or 30 mg ketorolac intravenously after the first CPT. The areas of pinprick hyperalgesia and CPT pain after the end of remifentanil infusion increased significantly compared to control (P < 0.001 and P = 0.005, respectively). Pretreatment with parecoxib or ketorolac reduced the postinfusion area of pinprick hyperalgesia (P < 0.001 and P = 0.001, respectively), compared to the remifentanil group. Parecoxib reduced the area significantly more than ketorolac (P = 0.009). In the CPT, pretreatment with parecoxib or ketorolac did not prevent postinfusion hyperalgesia. These results demonstrated OIH in both models, and may suggest that COX-2 inhibition is more important than COX-1 inhibition in reducing hyperalgesia. Remifentanil-induced hyperalgesia was demonstrated for both electrically induced pain and cold-pressor pain. Both parecoxib and ketorolac prevented hyperalgesia in the electrical model, parecoxib to a larger extent.
阿片类药物可能会增强疼痛敏感度，从而导致阿片类药物引起的痛觉过敏（OIH）。脊髓环氧化酶的激活可能在 OIH 的发展中起作用。本研究的目的是在电痛和冷痛模型中证明瑞芬太尼输注后引起的输注后痛觉过敏，并研究 COX-2（帕瑞昔布）或 COX-1（酮咯酸）抑制是否可以预防瑞芬太尼输注后的痛觉过敏。这项随机、双盲、安慰剂对照的交叉研究纳入了 16 名健康男性。每位受试者均经历了 4 个阶段：对照、瑞芬太尼、帕瑞昔布+瑞芬太尼和酮咯酸+瑞芬太尼。经皮电刺激诱发急性疼痛和针刺性痛觉过敏区域。在瑞芬太尼或生理盐水输注 30 分钟之前、期间和之后评估针刺性痛觉过敏区域。冷压试验（CPT）在输注前、结束时和输注后 1 小时进行。受试者在第一次 CPT 后静脉注射生理盐水、40mg 帕瑞昔布或 30mg 酮咯酸。与对照相比，瑞芬太尼输注结束后针刺性痛觉过敏区域和 CPT 疼痛显著增加（P<0.001 和 P=0.005）。与瑞芬太尼组相比，帕瑞昔布或酮咯酸预处理可减少输注后针刺性痛觉过敏区域（P<0.001 和 P=0.001）。帕瑞昔布的效果明显大于酮咯酸（P=0.009）。在 CPT 中，帕瑞昔布或酮咯酸预处理并不能预防输注后痛觉过敏。这些结果表明两种模型中均存在 OIH，并且可能表明 COX-2 抑制在减轻痛觉过敏方面比 COX-1 抑制更为重要。瑞芬太尼引起的痛觉过敏在电诱导疼痛和冷压疼痛模型中均得到证实。帕瑞昔布和酮咯酸均可预防电模型中的痛觉过敏，帕瑞昔布的效果更大。
