Logo image
Back
Dysregulation Of Prelimbic Cortical Activity Contributes to Pain-Induced Reinstatement of Ethanol Seeking in Male Mice with Spared Nerve Injury
Abstract   Peer reviewed

Dysregulation Of Prelimbic Cortical Activity Contributes to Pain-Induced Reinstatement of Ethanol Seeking in Male Mice with Spared Nerve Injury

Mitch Nothem, Andrea Borges, Jacob Brocious, Ejazz Moazzam, Anaahat Brar and Jacqueline Barker
The journal of pain, v 41, 106164
Mar 2026
DOI: https://doi.org/10.1016/j.jpain.2025.106164

Abstract

The majority of people with alcohol use disorder (AUD) also experience chronic pain. AUD is difficult to treat, particularly because relapse is hard to prevent. Clinical data show that chronic pain increases the probability of relapse. To model this, we developed a mouse paradigm of pain-induced relapse-related behavior using a conditioned-place preference (CPP) assay. Male mice underwent spared nerve injury (SNI) or sham surgery. Two weeks later, mice were conditioned with an antiallodynic dose of ethanol (0.5g/kg) followed by CPP testing and extinction training. Once preference for the ethanol-paired chamber was extinguished, mice were exposed to 10 individualized moderate-force (50% paw withdrawal threshold) painful mechanical stimulations immediately prior to reinstatement testing. SNI mice reinstated preference for the ethanol-paired chamber, while sham mice did not, suggesting chronic pain promotes pain-induced relapse-related behavior. To identify neural mechanisms underlying this effect, a separate cohort was implanted with microelectrode arrays targeting the prelimbic cortex (PrL). During the pain-reinstatement test, SNI mice displayed aberrant single-neuron firing and bursting compared to shams, suggesting dysregulated PrL activity during chronic pain may contribute to relapse-related behavior. A chemogenetic approach was used to demonstrate the role of the PrL. Here, SNI mice expressing Gi-coupled inhibitory DREADDs (or mCherry) in PrL, received the DREADD ligand deschloroclozapine or vehicle before reinstatement testing. Control virus and vehicle SNI mice reinstated after painful stimulation, however DREADD-expressing SNI mice failed to reinstate, indicating that silencing PrL prevents pain-induced reinstatement. Ongoing work is investigating the effect of inhibition of PRL in pain behaviors.

Metrics

1 Record Views

Details

Logo image