Abstract
A common clinical problem with opioid analgesics is the loss of analgesic efficacy after repeated dosing; when this occurs, it is not clear what principles should guide providing effective analgesia among opioid-dependent individuals. This within-subject inpatient study aimed to determine if physically dependent opioid abusers (n = 11) experience changes in oxycodone-induced analgesia during 2 oxycodone maintenance (30 mg orally 4 times per day) phases: initial stabilization (days 1-3) and after 6 weeks of chronic dosing. Six sessions (3 each phase), measured threshold, tolerance, and pain ratings for a Pressure Pain Test and Cold Pressor Test after a single double-blind dose of oxycodone 30 mg (initial stabilization) and 0, 30, and 60 mg (chronic dosing) given in place of a scheduled maintenance dose. Physiologic and opioid agonist effects were assessed during chronic dosing sessions. There was no analgesic response to oxycodone 30 mg. Oxycodone (60 mg) produced a 25% increase in peak Cold Pressor Test threshold compared with placebo, and significantly increased expired breath CO2, miosis, and ratings of abuse liability measures. These data suggest that more than twice the acute oxycodone maintenance dose is needed to produce robust acute analgesia, although adverse effects (eg, respiratory depression and abuse signals) may occur with lower doses. PERSPECTIVE: To understand sensitivity to opioid analgesia in opioid-dependent individuals, this article describes experimental pain, subjective and physiological responses during stabilization and after 6 weeks of oxycodone maintenance. Oxycodone produced euphoric effects and miosis with limited evidence of analgesia.