Brief Report: Is once daily enough? Assessing the impact of timing of methadone dose on pain sensitivity via quantitative sensory testing in persons with opioid use disorder

Published on April 28, 2026

Am J Addict. 2026 Apr 27. doi: 10.1111/ajad.70162. Online ahead of print.

ABSTRACT

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.

PMID:42046174 | DOI:10.1111/ajad.70162

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