Multi-molecular adaptations of long-term opioid use in chronic pain

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ID: 330777
2026
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Abstract
Millions of chronic pain patients are managed with opioids, yet the neuropsychological implications of stable long-term daily opioid consumption remain unknown. Here, we contrasted the psychosocial profiles and brain structure and function of 70 chronic back pain patients prescribed opioids (CBP+O, average current daily opioid exposure of 7.8 years) with tightly matched 70 opioid-naïve patients (CBP-O) and 30 healthy subjects. Despite CBP+O exhibiting only modestly worse psychosocial profiles and small differences in brain morphology relative to CBP-O, CBP+O showed stark differences in brain activity (ALFF). A large portion (38% of the variance) of this pattern was captured by a model using 19 receptor/transporter distributions. The patients' (across all 140 CBP) psychosocial profiles were summarized by three principal components (PCs, explaining 70% of variance): functional disability, pain quality, and negative affect. These PCs were respectively associated with serotonergic (5HT1a and 5HT6) and opioidergic (mu-opioid receptor, MOR) receptor-related activities. In additional analyses and new data, 5HT1a- and MOR-related activities tracked opioid dose, abstinence status, and tapering success, while 5HT6-related activity tracked pain intensity. Overall, our findings uncover molecularly defined brain circuits in opioid use and chronic pain.
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openalex_W7215043869 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Marwan N. Baliki, Andrew David Vigotsky, Gaëlle Rached, Rami Jabakhanji, Lejian Huang, Paulo Branco, Joana Barroso, Olivia Cong, Maria Centeno, Sam Cermak, James Griffith, Ajay D. Wasan, Thomas J. Schnitzer, A. Vania Apkarian
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Journal Brain research
Year 2026
DOI
10.1093/brain/awag339
URL
https://doi.org/10.1093/brain/awag339
Keywords Keywords not found

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