TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons

Abstract Increased activity and excitability (sensitisation) of a series of molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1 (TRPV1) in pain-sensing (nociceptive) primary sensory neurons are pivotal for developing pathological pain experiences in tissue...

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Autores principales:	Tianci Li, Gaoge Wang, Vivian Chin Chin Hui, Daniel Saad, Joao de Sousa Valente, Paolo La Montanara, Istvan Nagy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e8c624f13d84d4995ac9e642247fd89
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spelling	oai:doaj.org-article:0e8c624f13d84d4995ac9e642247fd892021-12-02T14:26:47ZTRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons10.1038/s41598-021-82829-62045-2322https://doaj.org/article/0e8c624f13d84d4995ac9e642247fd892021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82829-6https://doaj.org/toc/2045-2322Abstract Increased activity and excitability (sensitisation) of a series of molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1 (TRPV1) in pain-sensing (nociceptive) primary sensory neurons are pivotal for developing pathological pain experiences in tissue injuries. TRPV1 sensitisation is induced and maintained by two major mechanisms; post-translational and transcriptional changes in TRPV1 induced by inflammatory mediators produced and accumulated in injured tissues, and TRPV1 activation-induced feed-forward signalling. The latter mechanism includes synthesis of TRPV1 agonists within minutes, and upregulation of various receptors functionally linked to TRPV1 within a few hours, in nociceptive primary sensory neurons. Here, we report that a novel mechanism, which contributes to TRPV1 activation-induced TRPV1-sensitisation within ~ 30 min in at least ~ 30% of TRPV1-expressing cultured murine primary sensory neurons, is mediated through upregulation in cyclooxygenase 2 (COX2) expression and increased synthesis of a series of COX2 products. These findings highlight the importance of feed-forward signalling in sensitisation, and the value of inhibiting COX2 activity to control pain, in nociceptive primary sensory neurons in tissue injuries.Tianci LiGaoge WangVivian Chin Chin HuiDaniel SaadJoao de Sousa ValentePaolo La MontanaraIstvan NagyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tianci Li Gaoge Wang Vivian Chin Chin Hui Daniel Saad Joao de Sousa Valente Paolo La Montanara Istvan Nagy TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons
description	Abstract Increased activity and excitability (sensitisation) of a series of molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1 (TRPV1) in pain-sensing (nociceptive) primary sensory neurons are pivotal for developing pathological pain experiences in tissue injuries. TRPV1 sensitisation is induced and maintained by two major mechanisms; post-translational and transcriptional changes in TRPV1 induced by inflammatory mediators produced and accumulated in injured tissues, and TRPV1 activation-induced feed-forward signalling. The latter mechanism includes synthesis of TRPV1 agonists within minutes, and upregulation of various receptors functionally linked to TRPV1 within a few hours, in nociceptive primary sensory neurons. Here, we report that a novel mechanism, which contributes to TRPV1 activation-induced TRPV1-sensitisation within ~ 30 min in at least ~ 30% of TRPV1-expressing cultured murine primary sensory neurons, is mediated through upregulation in cyclooxygenase 2 (COX2) expression and increased synthesis of a series of COX2 products. These findings highlight the importance of feed-forward signalling in sensitisation, and the value of inhibiting COX2 activity to control pain, in nociceptive primary sensory neurons in tissue injuries.
format	article
author	Tianci Li Gaoge Wang Vivian Chin Chin Hui Daniel Saad Joao de Sousa Valente Paolo La Montanara Istvan Nagy
author_facet	Tianci Li Gaoge Wang Vivian Chin Chin Hui Daniel Saad Joao de Sousa Valente Paolo La Montanara Istvan Nagy
author_sort	Tianci Li
title	TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons
title_short	TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons
title_full	TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons
title_fullStr	TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons
title_full_unstemmed	TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons
title_sort	trpv1 feed-forward sensitisation depends on cox2 upregulation in primary sensory neurons
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0e8c624f13d84d4995ac9e642247fd89
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TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons

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