Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray

Adrianne R Wilson-Poe; Beth Wiese; Cherkaouia Kibaly; Lindsay Lueptow; Jeniffer Garcia; Preeti Anand; Catherine Cahill; Jose A Morón

doi:10.1097/PR9.0000000000000897

Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray

Pain Rep. 2021 Mar 5;6(1):e897. doi: 10.1097/PR9.0000000000000897. eCollection 2021 Jan-Feb.

Authors

Adrianne R Wilson-Poe¹, Beth Wiese², Cherkaouia Kibaly³, Lindsay Lueptow³, Jeniffer Garcia², Preeti Anand², Catherine Cahill³, Jose A Morón²

Affiliations

¹ Department of Neurobiology, Legacy Research Institute, Portland, OR, USA.
² Departments of Anesthesiology, Neuroscience and Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
³ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.

Abstract

Introduction: The periaqueductal gray (PAG) mediates the antinociceptive properties of analgesics, including opioids and cannabinoids. Administration of either opioids or cannabinoids into the PAG induces antinociception. However, most studies characterizing the antinociceptive properties of cannabinoids in the PAG have been conducted in naive animals. Few studies have reported on the role of CB1 receptors in the PAG during conditions which would prompt the administration of analgesics, namely, during pain states.

Objectives: To examine inflammatory pain-induced changes in CB1 receptor expression and function in the midbrain periaqueductal gray.

Methods: In this study, we used the Complete Freund Adjuvant model to characterize CB1 receptor expression and G-protein coupling during persistent inflammatory pain.

Results: Inflammatory pain induced an upregulation in the expression of synaptic CB1 receptors in the PAG. Despite this pain-induced change in CB1 expression, there was no corresponding upregulation of CB1 mRNA after the induction of inflammatory pain, suggesting a pain-induced recruitment of CB1 receptors to the synaptic sites within PAG neurons or increased coupling efficiency between the receptor and effector systems. Inflammatory pain also enhanced ventrolateral PAG CB1 receptor activity, as there was an increase in CP55,940-stimulated G-protein activation compared with pain-naïve control animals.

Conclusion: These findings complement a growing body of evidence which demonstrate pain-induced changes in brain regions that are responsible for both the analgesic and rewarding properties of analgesic pharmacotherapies. Because much of our understanding of the pharmacology of cannabinoids is based on studies which use largely pain-naïve male animals, this work fills in important gaps in the knowledge base by incorporating pain-induced adaptations and cannabinoid pharmacology in females.

Keywords: CB1; Cannabinoid; Inflammatory pain; PAG; Periaqueductal gray.

Abstract

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