Brief report shows tolerance decreases with pre-dose methadone during quantitative sensory testing, suggesting pain sensitivity issues in opioid use disorder.
BACKGROUND AND OBJECTIVES: Once-daily methadone dosing for opioid use disorder (OUD) may leave periods of inadequate analgesia. We tested whether experimental pain sensitivity differs across the inter-dose interval. METHODS: Twenty-five adults (52% female, 43.12 years old) with OUD receiving stable once-daily methadone completed thermal quantitative sensory testing at early post-dose and pre-dose. RESULTS: Heat pain threshold (MD -3.75°C; g = -0.78; p < .001) and tolerance (MD -0.92°C; g = -0.49; p = .018) were lower at pre-dose. Temporal summation and conditioned pain modulation did not differ. DISCUSSION AND CONCLUSIONS: Pain sensitivity increased pre-dose, consistent with a hyperalgesic window. SCIENTIFIC SIGNIFICANCE: Preliminary experimental evidence that once-daily methadone may contribute to cyclical hyperalgesia in persons with OUD.
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Costa et al. (2026) studied this question.
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