Dirks Jesper, Møiniche Steen, Hilsted Karen-Lisa, Dahl Jørgen B
Laboratory of Pain Physiology, Department of Anesthesiology and Intensive Care Medicine, Herlev University Hospital, Herlev, Denmark.
Anesthesiology. 2002 Dec;97(6):1591-6. doi: 10.1097/00000542-200212000-00035.
The relative importance of different nociceptive mechanisms for the intensity, duration, and character of postoperative pain is not well established. It has been suggested that sensitization of dorsal horn neurones may contribute to pain in the postoperative period. We hypothesized that wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia share a common mechanism, sensitization of central neurones, and consequently, that the short-acting opioid remifentanil would have comparable effects on hyperalgesia in both conditions.
In a randomized, controlled, double-blind trial, we assessed mechanical hyperalgesia in skin bordering the surgical wound, and an area of experimentally heat-induced secondary hyperalgesia on the thigh, in 12 patients who underwent abdominal hysterectomy within 5 days prior to the investigation. Observations were made before and during a drug challenge with remifentanil, which has been demonstrated to reduce the area of heat-induced secondary hyperalgesia in volunteers.
The area of skin with surgically-induced mechanical hyperalgesia, the area of heat-induced secondary hyperalgesia, and pain during cough, were significantly reduced during remifentanil infusion compared with placebo (P = 0.008, P = 0.006, and P = 0.002, respectively). The relative reduction (% of baseline) of the area of skin with surgically-induced hyperalgesia and heat-induced secondary hyperalgesia during infusion of remifentanil was significantly associated (R2 = 0.72, P = 0.001).
Although remifentanil is not a highly targeted "antihyperalgesic," these results support the hypothesis that both wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia may share common mechanisms, and that central neuronal sensitization may contribute to some aspects of postoperative pain. Antihyperalgesic drugs should be further developed and evaluated in clinical trials of postoperative pain.
不同伤害感受机制对术后疼痛的强度、持续时间及性质的相对重要性尚未明确确立。有研究表明，背角神经元的敏化可能在术后疼痛中起作用。我们推测，术后患者的伤口痛觉过敏与实验性热诱导继发性痛觉过敏具有共同机制，即中枢神经元敏化，因此，短效阿片类药物瑞芬太尼在两种情况下对痛觉过敏的影响具有可比性。
在一项随机、对照、双盲试验中，我们评估了12例在研究前5天内接受腹部子宫切除术患者手术伤口周围皮肤的机械性痛觉过敏，以及大腿上实验性热诱导继发性痛觉过敏区域。在给予瑞芬太尼药物激发前及激发过程中进行观察，瑞芬太尼已被证明可减少志愿者热诱导继发性痛觉过敏区域。
与安慰剂相比，输注瑞芬太尼期间，手术诱导机械性痛觉过敏皮肤区域、热诱导继发性痛觉过敏区域以及咳嗽时的疼痛均显著减轻（分别为P = 0.008、P = 0.006和P = 0.002）。输注瑞芬太尼期间，手术诱导痛觉过敏皮肤区域和热诱导继发性痛觉过敏区域的相对减少（相对于基线的百分比）显著相关（R2 = 0.72，P = 0.001）。
虽然瑞芬太尼并非高度靶向的“抗痛觉过敏”药物，但这些结果支持以下假设：术后患者的伤口痛觉过敏与实验性热诱导继发性痛觉过敏可能具有共同机制，且中枢神经元敏化可能在术后疼痛的某些方面起作用。应进一步研发抗痛觉过敏药物并在术后疼痛的临床试验中进行评估。
