Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Epigenetic Connections of the TRPA1 Ion Channel in Pain Transmission and Neurogenic Inflammation – A Therapeutic Perspective in Migraine?

Version 1 : Received: 6 October 2022 / Approved: 7 October 2022 / Online: 7 October 2022 (15:21:34 CEST)

A peer-reviewed article of this Preprint also exists.

Fila, M.; Pawlowska, E.; Szczepanska, J.; Blasiak, J. Epigenetic Connections of the TRPA1 Ion Channel in Pain Transmission and Neurogenic Inflammation — a Therapeutic Perspective in Migraine? Molecular Neurobiology 2023, doi:10.1007/s12035-023-03428-2. Fila, M.; Pawlowska, E.; Szczepanska, J.; Blasiak, J. Epigenetic Connections of the TRPA1 Ion Channel in Pain Transmission and Neurogenic Inflammation — a Therapeutic Perspective in Migraine? Molecular Neurobiology 2023, doi:10.1007/s12035-023-03428-2.

Abstract

Background: Transient receptor potential cation channel subfamily A member 1 (TRPA1) is expressed in trigeminal neurons and brain regions important in migraine pathogenesis and is activated by many migraine triggers. Epigenetic regulation of TRPA1 expression is important in pain transmission and neurogenic inflammation.Findings: TRPA1 channels change noxious stimuli into pain signals with the involvement of epigenetic regulation, including DNA methylation, histone modifications, and effects of micro RNAs (miRNAs) and long non-coding RNAs. TRPA1 may change epigenetic profile of many pain-related genes as it may modify enzymes establishing the epigenetic profile and expression of non-coding RNAs. TRPA1 may induce the release of calcitonin gene related peptide (CGRP), from trigeminal neurons and dural tissue. Therefore, epigenetic regulation of TRPA1 may play a role in efficacy and safety of anti-migraine therapies targeting TRP channels and CGRP. TRPA1 is also involved in neurogenic inflammation, important in migraine. The fundamental role of TRPA1 in inflammatory pain transmission may be epigenetically regulated. Conclusions: Epigenetic connections of TRPA1 may play a role in efficacy and safety of anti-migraine therapy targeting TRP channels or CGRP and they should be further explored for efficient and safe antimigraine treatment.

Keywords

epigenetics; TRP channels; TRPA1; pain transmission; neuropathic pain; neurogenic inflammation; migraine; DNA methylation; histone modification; micro RNA

Subject

Medicine and Pharmacology, Pathology and Pathobiology

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