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Effects of Short-Term Oxycodone Maintenance on Experimental Pain Responses in Physically Dependent Opioid Abusers

  • Marion A. Coe
    Correspondence
    Address reprint requests to Marion A. Coe, BA, 845 Angliana Ave, Lexington, KY 40508.
    Affiliations
    Department of Pharmacology, College of Medicine, University of Kentucky, Lexington, Kentucky

    Center on Drug and Alcohol Research, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Paul A. Nuzzo
    Affiliations
    Center on Drug and Alcohol Research, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Michelle R. Lofwall
    Affiliations
    Center on Drug and Alcohol Research, College of Medicine, University of Kentucky, Lexington, Kentucky

    Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, Kentucky

    Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Sharon L. Walsh
    Affiliations
    Department of Pharmacology, College of Medicine, University of Kentucky, Lexington, Kentucky

    Center on Drug and Alcohol Research, College of Medicine, University of Kentucky, Lexington, Kentucky

    Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, Kentucky

    Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, Kentucky

    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky
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      Highlights

      • Persons with opioid dependence underwent pain testing during oxycodone maintenance.
      • Analgesic testing occurred at stabilization and 6 weeks later.
      • Oxycodone produced euphoric effects and miosis without robust analgesia.
      • Differential tolerance is important for treatment of pain and opioid use disorder.

      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.

      Key words

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