Functional and Molecular Characterization of Mechanoinsensitive 'Silent' Nociceptors
| Autor: | Bassim Tazir, Francisco J. Taberner, Leoni Hammer, Paul A. Heppenstall, Paulina Schad, Ewan St. John Smith, Stefan G. Lechner, Alice Arcourt, Gerard Callejo, Vincenzo Prato, James R.F. Hockley |
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| Přispěvatelé: | Hockley, James [0000-0002-9578-6071], Smith, Ewan St John [0000-0002-2699-1979], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetics and Molecular Biology (all) Patch-Clamp Techniques Receptors Nicotinic Biochemistry Settore BIO/09 - Fisiologia Mechanotransduction Cellular Ion Channels Mice 0302 clinical medicine Ganglia Spinal MIA Mechanotransduction lcsh:QH301-705.5 inflammatory pain NGF Chemistry Piezo2 Nociceptors Biomechanical Phenomena Nicotinic acetylcholine receptor Nociception CHRNA3 Hyperalgesia Nociceptor medicine.symptom silent nociceptor Primary Cell Culture Pain Inflammation Mice Transgenic General Biochemistry Genetics and Molecular Biology Article nerve growth factor 03 medical and health sciences hyperalgesia mechanically insensitive nociceptor mechanotransduction Biochemistry Genetics and Molecular Biology (all) Evoked Potentials Somatosensory medicine Animals Retrograde tracing 030104 developmental biology Nerve growth factor lcsh:Biology (General) nervous system Gene Expression Regulation Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 21, Iss 11, Pp 3102-3115 (2017) |
| DOI: | 10.17863/cam.20746 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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