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Opioid-induced abnormal pain sensitivity
Joseph R. Holtman, MD, PhD1, Jaime Johnson, MS1, Thomas H. Kelly, PhD2, and Elzbieta Wala, PhD1. (1) Department of Anesthesiology, University of Kentucky, 800 Rose St Rm N-202, Lexington, KY 40536, (2) Behavioral Sciences, University of Kentucky, 134 College of Medicine Office Building 0086, Lexington, KY 40536
Opioids are the mainstay for treatment of moderate to severe pain. Widely accepted for use in acute and cancer pain, they are now increasingly prescribed for chronic nonmalignant pain, despite the risk of several negative health consequences (cognitive dysfunction, respiratory depression, tolerance, dependence, misuse/abuse). A potentially important consequence of opioid treatment is enhanced pain sensitivity (opioid-induced hyperalgesia, OIH). OIH could complicate clinical use of opioids and contribute to misuse/abuse. OIH has been readily demonstrated in several settings, characterized by dose (very low, high) and administration (acute, chronic), in rodents. Relatively little or no clinical data exists for OIH. We have performed a pilot, double-blind, randomized, cross-over study to address this question. Volunteers (12/gender) were administered IV morphine (0.3, 3 and 30mcg/kg) and placebo. A well-established experimental model of tonic pain, the cold pressor test (3.1-3.40C), was employed. Pain threshold (PTHR), pain tolerance (PTOL), pain intensity (a Visual Analog Scale, VAS), self-reported drug effects (the Opioid Agonist, OAS, and Opioid Withdrawal, OWS, scales) and vital signs were assessed at several time points (0, 5, 15, 30, 45, 60, 90, 120min). Baseline PTHR and PTOL were similar in male and female subjects. Morphine-induced hyperalgesia was evident as a decrease in PTHR and PTOL. Morphine analgesia was demonstrated by an increase in PTHR and PTOL. These effects were not reflected in the VAS. OIH appeared to be accompanied by a decrease in self-reported drug effect (OAS). Present data demonstrated OIH after administration of low-dose morphine in humans. This finding on development of OIH secondary to opioid exposure is an important issue. First, if OIH is produced during the course of clinical treatment it may actually worsen the chronic pain condition. Second, individual susceptibility to OIH may contribute to drug dependence and misuse/abuse in pain patients chronically treated with opioids. Future studies are warranted.