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bioRxiv · 10.1101/2020.09.05.267708

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

Li, T.·Wang, G.·Hui, V. C. C.·Saad, D.·de Sousa Valente, J.·La Montanara, P.·Nagy, I.
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Abstract

ABSRTRACTIncreased 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 minutes 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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Li, T., Wang, G., Hui, V. C. C., Saad, D., de Sousa Valente, J., La Montanara, P., Nagy, I.. 2020-09-05. TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons. https://doi.org/10.1101/2020.09.05.267708

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