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REV-ERB activation as a novel pharmacological approach for treating inflammatory pain

Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain,...

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Autores principales: Makhija, Sangeet, Griffett, Joshua D., Veerakanellore, Giri Babu, Burris, Thomas P., Elgendy, Bahaa, Griffett, Kristine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154555/
https://www.ncbi.nlm.nih.gov/pubmed/37153791
http://dx.doi.org/10.3389/fphar.2023.1171931
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author Makhija, Sangeet
Griffett, Joshua D.
Veerakanellore, Giri Babu
Burris, Thomas P.
Elgendy, Bahaa
Griffett, Kristine
author_facet Makhija, Sangeet
Griffett, Joshua D.
Veerakanellore, Giri Babu
Burris, Thomas P.
Elgendy, Bahaa
Griffett, Kristine
author_sort Makhija, Sangeet
collection PubMed
description Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients. Here, we show that the nuclear receptor REV-ERB can suppress the activation of the inflammasome when pharmacologically activated with small molecule agonists. Additionally, REV-ERB activation appears to have analgesic potential in a model of acute inflammatory pain, likely as a result of inflammasome suppression.
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spelling pubmed-101545552023-05-04 REV-ERB activation as a novel pharmacological approach for treating inflammatory pain Makhija, Sangeet Griffett, Joshua D. Veerakanellore, Giri Babu Burris, Thomas P. Elgendy, Bahaa Griffett, Kristine Front Pharmacol Pharmacology Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients. Here, we show that the nuclear receptor REV-ERB can suppress the activation of the inflammasome when pharmacologically activated with small molecule agonists. Additionally, REV-ERB activation appears to have analgesic potential in a model of acute inflammatory pain, likely as a result of inflammasome suppression. Frontiers Media S.A. 2023-04-19 /pmc/articles/PMC10154555/ /pubmed/37153791 http://dx.doi.org/10.3389/fphar.2023.1171931 Text en Copyright © 2023 Makhija, Griffett, Veerakanellore, Burris, Elgendy and Griffett. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Makhija, Sangeet
Griffett, Joshua D.
Veerakanellore, Giri Babu
Burris, Thomas P.
Elgendy, Bahaa
Griffett, Kristine
REV-ERB activation as a novel pharmacological approach for treating inflammatory pain
title REV-ERB activation as a novel pharmacological approach for treating inflammatory pain
title_full REV-ERB activation as a novel pharmacological approach for treating inflammatory pain
title_fullStr REV-ERB activation as a novel pharmacological approach for treating inflammatory pain
title_full_unstemmed REV-ERB activation as a novel pharmacological approach for treating inflammatory pain
title_short REV-ERB activation as a novel pharmacological approach for treating inflammatory pain
title_sort rev-erb activation as a novel pharmacological approach for treating inflammatory pain
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154555/
https://www.ncbi.nlm.nih.gov/pubmed/37153791
http://dx.doi.org/10.3389/fphar.2023.1171931
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