Prato, V., Taberner, F.J., Hockley, J.R.F. et al. (8 more authors) (2017) Functional and Molecular Characterization of Mechanoinsensitive “Silent” Nociceptors. Cell Reports, 21 (11). pp. 3102-3115. ISSN 2211-1247
Abstract
Mechanical and thermal hyperalgesia (pain hypersensitivity) are cardinal signs of inflammation. Although the mechanism underlying thermal hyperalgesia is well understood, the cellular and molecular basis of mechanical hyperalgesia is poorly described. Here, we have identified a subset of peptidergic C-fiber nociceptors that are insensitive to noxious mechanical stimuli under normal conditions but become sensitized to such stimuli when exposed to the inflammatory mediator nerve growth factor (NGF). Strikingly, NGF did not affect mechanosensitivity of other nociceptors. We show that these mechanoinsensitive “silent” nociceptors are characterized by the expression of the nicotinic acetylcholine receptor subunit alpha-3 (CHRNA3) and that the mechanically gated ion channel PIEZO2 mediates NGF-induced mechanosensitivity in these neurons. Retrograde tracing revealed that CHRNA3+ nociceptors account for ∼50% of all peptidergic nociceptive afferents innervating visceral organs and deep somatic tissues. Hence, our data suggest that NGF-induced “un-silencing” of CHRNA3+ nociceptors significantly contributes to the development of mechanical hyperalgesia during inflammation. Prato et al. find that mechanoinsensitive nociceptors account for ∼50% of all nociceptors in visceral organs and deep somatic tissues and are sensitized to mechanical stimuli by the inflammatory mediator NGF, suggesting that they significantly contribute to inflammation-induced mechanical hyperalgesia.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | nerve growth factor; NGF; silent nociceptor; Piezo2; mechanotransduction; inflammatory pain; hyperalgesia; CHRNA3 mechanically insensitive nociceptor; MIA |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Jan 2024 14:07 |
Last Modified: | 05 Jan 2024 14:07 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.celrep.2017.11.066 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:201356 |