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

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

Sci Rep

Nociception Group, Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Chelsea and Westminster Hospital, Imperial College London, 369 Fulham Road, London, SW10 9NH, UK.

Published: February 2021

AI Article Synopsis

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876133PMC
http://dx.doi.org/10.1038/s41598-021-82829-6DOI Listing

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