Endogenous µ-opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain

Cooper, A. H. , Hedden, N. S., Corder, G., Lamerand, S. R., Donahue, R. R., Morales-Medina, J. C., Selan, L., Prasoon, P. and Taylor, B. K. (2022) Endogenous µ-opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain. Journal of Neuroscience Research, 100(1), pp. 48-65. (doi: 10.1002/jnr.24846) (PMID:33957003)

Abstract

Tissue injury induces a long‐lasting latent sensitization (LS) of spinal nociceptive signaling that is kept in remission by an opposing µ‐opioid receptor (MOR) constitutive activity. To test the hypothesis that supraspinal sites become engaged, we induced hindpaw inflammation, waited 3 weeks for mechanical hypersensitivity to resolve, and then injected the opioid receptor inhibitors naltrexone, CTOP or β‐funaltrexamine subcutaneously, and/or into the cerebral ventricles. Intracerebroventricular injection of each inhibitor reinstated hypersensitivity and produced somatic signs of withdrawal, indicative of LS and endogenous opioid dependence, respectively. In naïve or sham controls, systemic naloxone (3 mg/kg) produced conditioned place aversion, and systemic naltrexone (3 mg/kg) increased Fos expression in the central nucleus of the amygdala (CeA). In LS animals tested 3 weeks after plantar incision, systemic naltrexone reinstated mechanical hypersensitivity and produced an even greater increase in Fos than in sham controls, particularly in the capsular subdivision of the right CeA. One third of Fos+ profiles co‐expressed protein kinase C delta (PKCδ), and 35% of PKCδ neurons co‐expressed tdTomato+ in Oprm1Cre::tdTomato transgenic mice. CeA microinjection of naltrexone (1 µg) reinstated mechanical hypersensitivity only in male mice and did not produce signs of somatic withdrawal. Intra‐CeA injection of the MOR‐selective inhibitor CTAP (300 ng) reinstated hypersensitivity in both male and female mice. We conclude that MORs in the capsular subdivision of the right CeA prevent the transition from acute to chronic postoperative pain.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cooper, Dr Andrew

Creator Roles

Cooper, A. H.: Conceptualization, Investigation, Visualization, Writing – original draft, Writing – review and editing

• Authors: Cooper, A. H., Hedden, N. S., Corder, G., Lamerand, S. R., Donahue, R. R., Morales-Medina, J. C., Selan, L., Prasoon, P., and Taylor, B. K.
• Subjects: Q Science > QP Physiology
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Neuroscience Research
• Publisher: Wiley
• ISSN: 0360-4012
• ISSN (Online): 1097-4547
• Published Online: 06 May 2021
• Copyright Holders: Copyright © 2021 Wiley Periodicals LLC
• First Published: First published in Journal of Neuroscience Research 100(1): 48-65
• Publisher Policy: Reproduced in accordance with the publisher copyright policy