Li X, Angst M S, Clark J D
Veterans Affairs, Palo Alto Health Care System and Department of Anesthesiology, Stanford University, Palo Alto, California 94304, USA.
Anesth Analg. 2001 Jul;93(1):204-9. doi: 10.1097/00000539-200107000-00040.
Opioids occupy a position of unsurpassed clinical utility in the treatment of pain of many etiologies. However, recent reports in laboratory animals and humans have documented the occurrence of hyperalgesia when the administration of opioids is abruptly tapered or discontinued, a condition known as opioid-induced hyperalgesia (OIH). In these studies we documented that rats administered morphine (40 mg. kg(-1). day(-1) for 6 days) via subcutaneous osmotic minipumps demonstrated thermal hyperalgesia and mechanical allodynia for several days after the cessation of morphine administration. Additional experiments using a rat model of incisional pain showed that that attributable to OIH were additive with the hyperalgesia and allodynia that resulted from incision. In our final experiments we observed that if naloxone is administered chronically before incision then discontinued (20 mg. kg(-1). day(-1) for 6 days), the hyperalgesia and allodynia that result from hind paw incision was markedly reduced. In contrast, naloxone 1 mg/kg administered acutely after hind paw incision increased hyperalgesia and allodynia. We conclude that the chronic administration of exogenous opioid receptor agonists and antagonists before incision can alter the hyperalgesia and allodynia observed in this pain model, perhaps by altering intrinsic opioidergic systems involved in setting thermal and mechanical nociceptive thresholds.
The chronic administration of opioids followed by abrupt cessation can lead to a state of hyperalgesia. In these studies we demonstrate that the hyperalgesia from opioid cessation and from hind paw incision are additive in rats. We suggest that failure to take into consideration preoperative opioid use can lead to excessive postoperative pain.
阿片类药物在治疗多种病因引起的疼痛方面具有无与伦比的临床效用。然而，最近在实验动物和人类中的报告记录了在阿片类药物突然减量或停药时会出现痛觉过敏，这种情况被称为阿片类药物诱导的痛觉过敏（OIH）。在这些研究中，我们记录到通过皮下渗透微型泵给予吗啡（40毫克·千克⁻¹·天⁻¹，持续6天）的大鼠在吗啡给药停止后的几天内表现出热痛觉过敏和机械性异常性疼痛。使用切口痛大鼠模型的额外实验表明，由OIH引起的痛觉过敏和异常性疼痛与切口导致的痛觉过敏和异常性疼痛具有叠加性。在我们最后的实验中，我们观察到如果在切口前长期给予纳洛酮然后停药（20毫克·千克⁻¹·天⁻¹，持续6天），后爪切口引起的痛觉过敏和异常性疼痛会明显减轻。相比之下，后爪切口后急性给予1毫克/千克纳洛酮会增加痛觉过敏和异常性疼痛。我们得出结论，在切口前长期给予外源性阿片受体激动剂和拮抗剂可以改变在这个疼痛模型中观察到的痛觉过敏和异常性疼痛，可能是通过改变参与设定热和机械性伤害性感受阈值的内在阿片肽系统。
长期给予阿片类药物后突然停药可导致痛觉过敏状态。在这些研究中，我们证明了大鼠中阿片类药物停药引起的痛觉过敏和后爪切口引起的痛觉过敏具有叠加性。我们认为，未考虑术前使用阿片类药物可能导致术后疼痛过度。
