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REGIONAL ANESTHESIA

Opioid-Induced Hyperalgesia and Incisional Pain

Veterans Affairs, Palo Alto Health Care System and Department of Anesthesiology, Stanford University, Palo Alto, California

Address correspondence and reprint requests to J. David Clark, MD, PhD, VAPAHCS, Anesthesiology, 112A, 3801 Miranda Avenue, Palo Alto, CA 94304. Address e-mail to djclark{at}stanford.edu

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.

Implications: The chronic administration of opioids followed by abrupt cessation can lead toa state of hyperalgesia. In these studies we demonstrate that the hyperalgesiafrom opioid cessation and from hind paw incision are additive in rats. Wesuggest that failure to take into consideration preoperative opioid use canlead to excessive postoperative pain.

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