Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
J Pain. 2011 Jan;12(1):108-15. doi: 10.1016/j.jpain.2010.05.006.
Some recent studies suggested a role of the endogenous opioid system in modulating opioid-induced hyperalgesia (OIH). In order to test this hypothesis, we conducted a prospective randomized, placebo-controlled, 2-way crossover study in healthy human volunteers. We utilized a well-established model of inducing OIH after a brief exposure to the μ-opioid agonist remifentanil using intradermal electrical stimulation. Patients were exposed to a randomized 90-minute infusion of remifentanil or saline placebo during 2 separate occasions. Development of OIH was quantified using changes in the average radius of the area of secondary hyperalgesia generated by electrical pain stimulation. A 23.6% (20.2) increase in area of secondary hyperalgesia over baseline was observed in the postinfusion period of the remifentanil session, demonstrating development of OIH (P = .03). In order to test endogenous opioid system modulation of OIH, patients were given a 1-time bolus of naloxone, which had no effect on the size of the hyperalgesic lesion in either the remifentinal or placebo session. These results suggested that the endogenous opioid system did not appear to modulate OIH.
Experimental evidence suggested that the endogenous opioid system did not significantly affect opioid-induced hyperalgesia. Consequently, this study suggested that alternative mechanisms such as pronociceptive stimulation and neuroplastic changes might be responsible for expression of OIH.
一些最近的研究表明，内源性阿片系统在调节阿片类药物引起的痛觉过敏（OIH）中起作用。为了验证这一假设，我们在健康的人类志愿者中进行了一项前瞻性随机、安慰剂对照、2 向交叉研究。我们利用一种经过充分验证的模型，即在短暂暴露于μ阿片受体激动剂瑞芬太尼后，通过皮内电刺激来诱导 OIH。患者在 2 次单独的情况下接受随机 90 分钟的瑞芬太尼或盐水安慰剂输注。使用电疼痛刺激产生的继发性超敏反应区域的平均半径变化来量化 OIH 的发展。在瑞芬太尼输注后的输注期，观察到继发性超敏反应区域增加了 23.6%（20.2），表明发生了 OIH（P=0.03）。为了测试内源性阿片系统对 OIH 的调节作用，患者给予单次纳洛酮推注，纳洛酮对瑞芬太尼或安慰剂输注期的痛觉过敏病变大小均无影响。这些结果表明，内源性阿片系统似乎没有调节 OIH。
实验证据表明，内源性阿片系统对阿片类药物引起的痛觉过敏没有显著影响。因此，本研究表明，替代机制，如促伤害性刺激和神经可塑性变化，可能是 OIH 表达的原因。
