Sustained morphine exposure alters spinal NMDA receptor and astrocyte expression and exacerbates chronic pain behavior in female rats

Gonçalves, Sara V.; Woodhams, Stephen G.; Li, Li; Hathway, Gareth J.; Chapman, Victoria

Abstract

IntroductionSustained opioid use has long-term negative impacts on future pain experience, particularly in women. This study aimed to investigate the underlying spinal neurobiology of this clinical observation in an experimental model of joint pain.ObjectivesIn this study, we tested the hypothesis that sustained opioid treatment exacerbates chronic pain responses and alters spinal cord dorsal horn astrogliosis and the expression of GluN2B-containing N-methyl-d-aspartate receptors in female rats.MethodsSubcutaneous morphine (3 mg/kg) or saline was administered twice daily for 1 week before inducing a model of joint knee pain (intra-articular injection of 2 mg of monosodium iodoacetate [MIA]) in adult female Sprague-Dawley rats, with pain-free controls receiving 50 µL of saline. Pain behavior (weight-bearing and mechanical paw withdrawal thresholds) was measured at baseline and at intervals thereafter. Twice-daily morphine/saline treatment was continued for up to 3 weeks after intra-articular injections, and spinal cord tissue was collected for Western blot analyses.ResultsArea under the curve analysis of weight-bearing asymmetry confirmed a significant exacerbation of pain behavior in the morphine/MIA group, compared with the saline/MIA group (F(3,18) = 46.3, P ConclusionThese data suggest that sustained morphine treatment in female rats drives spinal cord plasticity, including spinal astrogliosis and the expression of GluN2B-containing N-methyl-d-aspartate receptors, priming the dorsal horn to incoming sensory inputs and producing exacerbated pain responses.

Citation

Gonçalves, S. V., Woodhams, S. G., Li, L., Hathway, G. J., & Chapman, V. (2024). Sustained morphine exposure alters spinal NMDA receptor and astrocyte expression and exacerbates chronic pain behavior in female rats. PAIN Reports, 9(2), Article e1145. https://doi.org/10.1097/pr9.0000000000001145

• Journal Article Type: Article
• Acceptance Date: Jan 14, 2024
• Online Publication Date: Mar 12, 2024
• Publication Date: Apr 1, 2024
• Deposit Date: Jan 25, 2024
• Publicly Available Date: Mar 25, 2024
• Journal: PAIN Reports
• Electronic ISSN: 2471-2531
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 2
• Article Number: e1145
• DOI: https://doi.org/10.1097/pr9.0000000000001145
• Keywords: Opioids; NMDA receptors; astrocytes; females; chronic pain
• Public URL: https://nottingham-repository.worktribe.com/output/30147277
• PMID: 38482044