Neuropathic pain has sex-specific effects on oxycodone-seeking and non-drug-seeking ensemble neurons in the dorsomedial prefrontal cortex of mice. Addict Biol 2024 Aug;29(8):e13430
Date
08/10/2024Pubmed ID
39121884Pubmed Central ID
PMC11315577DOI
10.1111/adb.13430Scopus ID
2-s2.0-85200756850 (requires institutional sign-in at Scopus site)Abstract
Approximately 50 million Americans suffer from chronic pain, and nearly a quarter of chronic pain patients have reported misusing opioid prescriptions. Repeated drug seeking is associated with reactivation of an ensemble of neurons sparsely scattered throughout the dorsomedial prefrontal cortex (dmPFC). Prior research has demonstrated that chronic pain increases intrinsic excitability of dmPFC neurons, which may increase the likelihood of reactivation during drug seeking. We tested the hypothesis that chronic pain would increase oxycodone-seeking behaviour and that the pain state would differentially increase intrinsic excitability in dmPFC drug-seeking ensemble neurons. TetTag mice self-administered intravenous oxycodone. After 7 days of forced abstinence, a drug-seeking session was performed, and the ensemble was tagged. Mice received spared nerve injury (SNI) to induce chronic pain during the period between the first and second seeking session. Following the second seeking session, we performed electrophysiology on individual neurons within the dmPFC to assess intrinsic excitability of the drug-seeking ensemble and non-ensemble neurons. SNI had no impact on sucrose seeking or intrinsic excitability of dmPFC neurons from these mice. In females, SNI increased oxycodone seeking and intrinsic excitability of non-ensemble neurons. In males, SNI had no impact on oxycodone seeking or neuron excitability. Data from females are consistent with clinical reports that chronic pain can promote drug craving and relapse and support the hypothesis that chronic pain itself may lead to neuroadaptations which promote opioid seeking.
Author List
Sarka BC, Liu S, Banerjee A, Stucky CL, Liu QS, Olsen CMAuthors
Anjishnu Banerjee PhD Associate Professor in the Data Science Institute department at Medical College of WisconsinChristopher M. Olsen PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Analgesics, OpioidAnimals
Chronic Pain
Drug-Seeking Behavior
Female
Male
Mice
Neuralgia
Neurons
Oxycodone
Prefrontal Cortex
Self Administration
Sex Factors
