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

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 cannabi...

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Autores principales: Wilson-Poe, Adrianne R., Wiese, Beth, Kibaly, Cherkaouia, Lueptow, Lindsay, Garcia, Jeniffer, Anand, Preeti, Cahill, Catherine, Morón, Jose A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939232/
https://www.ncbi.nlm.nih.gov/pubmed/33693301
http://dx.doi.org/10.1097/PR9.0000000000000897
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author Wilson-Poe, Adrianne R.
Wiese, Beth
Kibaly, Cherkaouia
Lueptow, Lindsay
Garcia, Jeniffer
Anand, Preeti
Cahill, Catherine
Morón, Jose A.
author_facet Wilson-Poe, Adrianne R.
Wiese, Beth
Kibaly, Cherkaouia
Lueptow, Lindsay
Garcia, Jeniffer
Anand, Preeti
Cahill, Catherine
Morón, Jose A.
author_sort Wilson-Poe, Adrianne R.
collection PubMed
description 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.
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spelling pubmed-79392322021-03-09 Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray Wilson-Poe, Adrianne R. Wiese, Beth Kibaly, Cherkaouia Lueptow, Lindsay Garcia, Jeniffer Anand, Preeti Cahill, Catherine Morón, Jose A. Pain Rep Basic Science 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. Wolters Kluwer 2021-03-05 /pmc/articles/PMC7939232/ /pubmed/33693301 http://dx.doi.org/10.1097/PR9.0000000000000897 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain. https://creativecommons.org/licenses/by-nd/4.0/This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0 (CC BY-ND) (https://creativecommons.org/licenses/by-nd/4.0/) which allows for redistribution, commercial, and noncommercial, as long as it is passed along unchanged and in whole, with credit to the author.
spellingShingle Basic Science
Wilson-Poe, Adrianne R.
Wiese, Beth
Kibaly, Cherkaouia
Lueptow, Lindsay
Garcia, Jeniffer
Anand, Preeti
Cahill, Catherine
Morón, Jose A.
Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray
title Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray
title_full Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray
title_fullStr Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray
title_full_unstemmed Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray
title_short Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray
title_sort effects of inflammatory pain on cb1 receptor in the midbrain periaqueductal gray
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939232/
https://www.ncbi.nlm.nih.gov/pubmed/33693301
http://dx.doi.org/10.1097/PR9.0000000000000897
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