Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation

This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) in murine temporomandibular joint (TMJ) inflammatory hyperalgesia and the influence of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Two distinct murine models of TMJ pain and inflammation (zymosan an...

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Autores principales:	Xenia Kodji, Zizheng Kee, Robyn McKenna, Joao de Sousa Valente, Harriet Ravenscroft, Hayley McMillan, John Gamble, Yvonne Dombrowski, Paul Moynagh, David Brough, Fionnuala T. Lundy, Susan D. Brain, Ikhlas A. El Karim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	temporomandibular arthritis TRPA1 NLRP inflammasome mouse Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/26fbdb45b27d4d6c906fb94d82b206c3
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spelling	oai:doaj.org-article:26fbdb45b27d4d6c906fb94d82b206c32021-11-25T18:39:06ZEvidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation10.3390/ph141110731424-8247https://doaj.org/article/26fbdb45b27d4d6c906fb94d82b206c32021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1073https://doaj.org/toc/1424-8247This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) in murine temporomandibular joint (TMJ) inflammatory hyperalgesia and the influence of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Two distinct murine models of TMJ pain and inflammation (zymosan and CFA) were established. Spontaneous pain-like behaviours were observed as unilateral front paw cheek wipes. Ipsilateral cheek blood flow was used as a measure of ongoing inflammation, which, to our knowledge, is a novel approach to assessing real-time inflammation in the TMJ. Joint tissue and trigeminal ganglia were collected for ex vivo investigation. Both zymosan and CFA induced a time-dependent increase in hyperalgesia and inflammation biomarkers. Zymosan induced a significant effect after 4 h, correlating with a significantly increased IL-1β protein expression. CFA (50 µg) induced a more sustained response. The TRPA1 receptor antagonist A967079 significantly inhibited hyper-nociception. The NLRP3 inhibitor MCC950 similarly inhibited hyper-nociception, also attenuating inflammatory markers. In the trigeminal ganglia, CFA-induced CGRP expression showed trends of inhibition by A967079, whilst lba1 immunofluorescence was significantly inhibited by A967079 and MCC950, where the effect of TRPA1 inhibition lasted up to 14 days. Our results show that stimulation of TRPA1 is key to the TMJ pain. However, the inflammasome inhibitor exhibited similar properties in attenuating these pain-like behaviours, in addition to some inflammatory markers. This indicates that in addition to the therapeutic targeting of TRPA1, NLRP3 inhibition may provide a novel therapeutic strategy for TMJ inflammation and pain.Xenia KodjiZizheng KeeRobyn McKennaJoao de Sousa ValenteHarriet RavenscroftHayley McMillanJohn GambleYvonne DombrowskiPaul MoynaghDavid BroughFionnuala T. LundySusan D. BrainIkhlas A. El KarimMDPI AGarticletemporomandibular arthritisTRPA1NLRPinflammasomemouseMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1073, p 1073 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	temporomandibular arthritis TRPA1 NLRP inflammasome mouse Medicine R Pharmacy and materia medica RS1-441
spellingShingle	temporomandibular arthritis TRPA1 NLRP inflammasome mouse Medicine R Pharmacy and materia medica RS1-441 Xenia Kodji Zizheng Kee Robyn McKenna Joao de Sousa Valente Harriet Ravenscroft Hayley McMillan John Gamble Yvonne Dombrowski Paul Moynagh David Brough Fionnuala T. Lundy Susan D. Brain Ikhlas A. El Karim Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation
description	This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) in murine temporomandibular joint (TMJ) inflammatory hyperalgesia and the influence of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Two distinct murine models of TMJ pain and inflammation (zymosan and CFA) were established. Spontaneous pain-like behaviours were observed as unilateral front paw cheek wipes. Ipsilateral cheek blood flow was used as a measure of ongoing inflammation, which, to our knowledge, is a novel approach to assessing real-time inflammation in the TMJ. Joint tissue and trigeminal ganglia were collected for ex vivo investigation. Both zymosan and CFA induced a time-dependent increase in hyperalgesia and inflammation biomarkers. Zymosan induced a significant effect after 4 h, correlating with a significantly increased IL-1β protein expression. CFA (50 µg) induced a more sustained response. The TRPA1 receptor antagonist A967079 significantly inhibited hyper-nociception. The NLRP3 inhibitor MCC950 similarly inhibited hyper-nociception, also attenuating inflammatory markers. In the trigeminal ganglia, CFA-induced CGRP expression showed trends of inhibition by A967079, whilst lba1 immunofluorescence was significantly inhibited by A967079 and MCC950, where the effect of TRPA1 inhibition lasted up to 14 days. Our results show that stimulation of TRPA1 is key to the TMJ pain. However, the inflammasome inhibitor exhibited similar properties in attenuating these pain-like behaviours, in addition to some inflammatory markers. This indicates that in addition to the therapeutic targeting of TRPA1, NLRP3 inhibition may provide a novel therapeutic strategy for TMJ inflammation and pain.
format	article
author	Xenia Kodji Zizheng Kee Robyn McKenna Joao de Sousa Valente Harriet Ravenscroft Hayley McMillan John Gamble Yvonne Dombrowski Paul Moynagh David Brough Fionnuala T. Lundy Susan D. Brain Ikhlas A. El Karim
author_facet	Xenia Kodji Zizheng Kee Robyn McKenna Joao de Sousa Valente Harriet Ravenscroft Hayley McMillan John Gamble Yvonne Dombrowski Paul Moynagh David Brough Fionnuala T. Lundy Susan D. Brain Ikhlas A. El Karim
author_sort	Xenia Kodji
title	Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation
title_short	Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation
title_full	Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation
title_fullStr	Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation
title_full_unstemmed	Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation
title_sort	evidence that a trpa1-mediated murine model of temporomandibular joint pain involves nlrp3 inflammasome activation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/26fbdb45b27d4d6c906fb94d82b206c3
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Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation

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