Citation

Jammoul M, Jammoul D, Wang KK, Kobeissy F, DePalma RG. Biol. Psychiatry 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, Elsevier Publishing)

DOI

10.1016/j.biopsych.2023.05.013

PMID

37217015

Abstract

Traumatic brain injury (TBI) and opioid use disorders (OUDs) comprise twin plagues causing considerable morbidity and mortality worldwide. As interactions between TBI and OUD are uncharted, we review the possible mechanisms by which TBI may stimulate the development of OUD and discuss the interaction or crosstalk between these two processes. Central nervous system (CNS) damage due to TBI appears to drive adverse effects of subsequent OUD and opioid use/misuse affecting several molecular pathways. Pain, a neurological consequence of TBI, is a risk factor that increases the likelihood of opioid use/misuse after TBI. Other comorbidities including depression, anxiety, post-traumatic stress disorder, and sleep disturbances are also associated with deleterious outcomes. We examine the hypothesis that a TBI "first hit" induces a neuroinflammatory process involving microglial priming, which upon a "second hit"-related to opioid exposure-, exacerbates neuroinflammation, modifies synaptic plasticity, and spreads tau aggregates to promote neurodegeneration. As TBI also impairs myelin repair by oligodendrocytes, it may reduce or degrade white matter integrity in the reward circuit resulting in behavioral changes. Along with approaches focused on specific patient symptoms, understanding the CNS effects post-TBI offers a promise of improved management for individuals with OUD.

Language: en

Keywords

opioids; traumatic brain injury; inflammation; microglia; opioid use disorders; pain