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.

Functional and Molecular Characterization of Mechanoinsensitive “Silent” Nociceptors / Prato, Vincenzo; Taberner, Francisco J.; Hockley, James R. F.; Callejo, Gerard; Arcourt, Alice; Tazir, Bassim; Hammer, Leonie; Schad, Paulina; Heppenstall, Paul A.; Smith, Ewan S.; Lechner, Stefan G.. - In: CELL REPORTS. - ISSN 2211-1247. - 21:11(2017), pp. 3102-3115. [10.1016/j.celrep.2017.11.066]

Functional and Molecular Characterization of Mechanoinsensitive “Silent” Nociceptors

Heppenstall, Paul A.;
2017

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.
21
11
3102
3115
https://www.sciencedirect.com/science/article/pii/S2211124717317187?via%3Dihub
Prato, Vincenzo; Taberner, Francisco J.; Hockley, James R. F.; Callejo, Gerard; Arcourt, Alice; Tazir, Bassim; Hammer, Leonie; Schad, Paulina; Heppenstall, Paul A.; Smith, Ewan S.; Lechner, Stefan G.
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S2211124717317187-main.pdf

accesso aperto

Descrizione: Open Access
Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 5.39 MB
Formato Adobe PDF
5.39 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11767/87766
Citazioni
  • ???jsp.display-item.citation.pmc??? 40
  • Scopus 67
  • ???jsp.display-item.citation.isi??? 65
social impact