Hood David D, Curry Regina, Eisenach James C
Department of Anesthesiology and Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Anesth Analg. 2003 Sep;97(3):810-815. doi: 10.1213/01.ANE.0000078811.80093.88.
Opioids administered during surgery may be beneficial by preempting postoperative pain or detrimental by causing acute tolerance. We used a stable model of hyperalgesia in volunteers to test whether acute opioid exposure also results in such pain sensitization over a period of hours in humans. Ten healthy volunteers were studied. Areas of mechanical hyperalgesia and allodynia were induced by topical capsaicin application plus intermittent heating. Computer-controlled IV remifentanil infusion was titrated to a targeted plasma concentration that reduced pain report to noxious heat by 70% and was maintained at this level for 60-100 min. Areas of hyperalgesia and allodynia were measured during and after remifentanil infusion. Remifentanil (targeted concentration of 3.1 +/- 1.2 ng/mL) reduced areas of hyperalgesia and allodynia by 33% +/- 31% and 65% +/- 28%, respectively, during infusion (P < 0.05). Areas of hyperalgesia and allodynia continuously enlarged 4 h after remifentanil was stopped, to 180% +/- 47% and 180% +/- 86%, respectively. This study demonstrates that acute opioid exposure enhances hypersensitivity for hours after exposure. If applicable to the surgical setting, this could increase the dose of opioid required for postoperative analgesia and enhance, rather than inhibit, postoperative pain.
手术期间使用阿片类药物可能通过预防术后疼痛而有益，也可能因导致急性耐受性而有害。我们在志愿者中使用了一种稳定的痛觉过敏模型，以测试急性阿片类药物暴露在数小时内是否也会导致人类出现这种疼痛敏化。研究了10名健康志愿者。通过局部应用辣椒素加间歇性加热诱导机械性痛觉过敏和异常性疼痛区域。计算机控制静脉输注瑞芬太尼，滴定至目标血浆浓度，使对有害热的疼痛报告降低70%，并维持该水平60 - 100分钟。在瑞芬太尼输注期间和之后测量痛觉过敏和异常性疼痛区域。输注期间，瑞芬太尼（目标浓度为3.1±1.2 ng/mL）分别使痛觉过敏和异常性疼痛区域减少33%±31%和65%±28%（P<0.05）。瑞芬太尼停药4小时后，痛觉过敏和异常性疼痛区域持续扩大，分别达到180%±47%和180%±86%。这项研究表明，急性阿片类药物暴露在暴露后数小时内会增强超敏反应。如果适用于手术环境，这可能会增加术后镇痛所需的阿片类药物剂量，并增强而非抑制术后疼痛。
