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Genetic identification of mechanoINSENSITIVE ' silent’ nociceptors”

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  • Genetic identification of mechanoINSENSITIVE ' silent’ nociceptors”

    Summary https://www.ncbi.nlm.nih.gov/pmc/art...VC1CXAUN86n_Ro


    Mechanical and thermal hyperalgesia (pain hypersensitivity) are cardinal signs of inflammation. While 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 th.at 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 suggests that NGF-induced ‘un-silencing’ of CHRNA3+ nociceptors significantly contributes to the development of mechanical hyperalgesia during inflammation.

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    Simplicity is the ultimate sophistication. L VINCI
    We are to admit no more causes of natural things than such as are both true and sufficient to explain their appearances. I NEWTON

    Everything should be made as simple as possible, but not a bit simpler.
    If you can't explain it simply, you don't understand it well enough. Albert Einstein
    bernard

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