History of opioid use disorder correlates with altered neuroimmune signatures in the human dorsal root ganglia

Allison M Barry; Mandee K. Schaub; Joseph B. Lesnak; Erin Vines; Asta Arendt-Tranholm; Úrzula Franco‐Enzástiga; Jayden A. O'Brien; Ishwarya Sankaranarayanan; Stephanie I. Shiers; Arthur Silveira Prudente; Julia Regina Sondermann; Michael Wilde; Feng Xian; Tariq Khan; Anna M. Cervantes; Geoffrey A. Funk; Peter Horton; Steve Davidson; Temugin Berta; Gregory O. Dussor; Manuela Schmidt; Theodore John Price

doi:10.64898/2026.10.10.758227

NeurosciencebioRxivOct 16, 2026

Preprint

History of opioid use disorder correlates with altered neuroimmune signatures in the human dorsal root ganglia

Allison M Barry iD, Mandee K. Schaub, Joseph B. Lesnak iD, Erin Vines, Asta Arendt-Tranholm iD, Úrzula Franco‐Enzástiga iD, Jayden A. O'Brien iD, Ishwarya Sankaranarayanan iD, Stephanie I. Shiers iD, Arthur Silveira Prudente iD, Julia Regina Sondermann iD, Michael Wilde, Feng Xian iD, Tariq Khan, Anna M. Cervantes iD, Geoffrey A. Funk iD, Peter Horton iD, Steve Davidson iD, Temugin Berta iD, Gregory O. Dussor iD, Manuela Schmidt iD, Theodore John Price iD

Abstract

Understanding mechanisms for the negative reinforcing effects of opioids are fundamental to improving patient care. Using human dorsal root ganglia (DRG) from donors with and without opioid use disorder (OUD), we set out to examine functional and molecular correlates of chronic opioid use. At a molecular level, we detected disrupted immune signatures throughout cells in the peripheral nervous system (PNS), spanning glial-neuroimmune interactions to changes in non-neuronal senescence. At the physiological level these changes are paired with sensitization of DRG sensory neurons. Our findings reveal a neuro-inflammatory state in the PNS of individuals with OUD. Targeting therapeutics towards these PNS-based mechanisms could be an approach to alleviating the negative reinforcing effects of opioids.

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