Hyperalgesia in Heroin Dependent Patients and the Effects of Opioid Substitution Therapy

Abstract

Evidence suggests that patients on opiate maintenance therapy for the treatment of addiction present with opioid-induced hyperalgesia. This study compared the experimental (cold-pressor, electrical stimulation) pain responses of 82 treatment-seeking heroin-dependent adults, randomized to methadone (METH, n = 11) or buprenorphine (BUP, n = 64) therapy, with matched drug free controls (n = 21). Heroin-dependent participants were evaluated at baseline (treatment entry), medication (METH or BUP) stabilization (4–8 weeks), and chronic administration (12–18 weeks), at trough (just prior to dosing) and peak (3 hours after dosing) plasma levels. Collection of the control group’s pain responses occurred twice during a single session, 3 hours apart. Baseline comparisons indicate that heroin-dependent individuals demonstrate significantly shorter latencies to threshold and tolerance for cold-pressor pain than the control group. Across pain stimuli and time points, little change in pain responses was found over time, the exception being cold pressor pain tolerance, for which hyperalgesia significantly increased at trough METH/BUP levels in both groups as they stabilized in treatment. We conclude that heroin-dependent individuals are hyperalgesic, and that once stabilized in treatment, are not different in pain responses regardless of treatment agent. The effects of nonpharmacologic therapy and previous heroin use may explain increased hyperalgesia found with treatment.

Perspective

To better understand the clinical phenomenon of opioid-induced hyperalgesia, this article describes experimental pain responses of heroin-dependent participants both prior to and over the course of maintenance therapy with methadone or buprenorphine. Hyperalgesia is present with illicit and treatment opioid use, and does not appear to appreciably improve over the course of treatment.