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Peripheral sensitisation of nociceptors via G-protein-dependent potentiation of mechanotransduction currents.

Authors
  • Lechner, Stefan G1
  • Lewin, Gary R
  • 1 Department of Neuroscience, Max-Delbrück-Center for Molecular Medicine, Robert Rössle Str. 10, 3125 Berlin, Germany.
Type
Published Article
Journal
The Journal of Physiology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jul 15, 2009
Volume
587
Issue
Pt 14
Pages
3493–3503
Identifiers
DOI: 10.1113/jphysiol.2009.175059
PMID: 19505980
Source
Medline
License
Unknown

Abstract

Mechanical stimuli impinging on the skin are converted into electrical signals by mechanically gated ion channels located at the peripheral nerve endings of dorsal root ganglion (DRG) neurons. Under inflammatory conditions sensory neurons are commonly sensitised to mechanical stimuli; a putative mechanism that may contribute to such sensitisation of sensory neurons is enhanced responsiveness of mechanotransduction ion channels. Here we show that the algogens UTP and ATP potentiate mechanosensitive RA currents in peptidergic nociceptive DRG neurons and reduce thresholds for mechanically induced action potential firing in these neurones. Pharmacological characterisation suggests that this effect is mediated by the Gq-coupled P2Y(2) nucleotide receptor. Moreover, using the in vitro skin nerve technique, we show that UTP also increases action potential firing rates in response to mechanical stimuli in a subpopulation of skin C-fibre nociceptors. Together our findings suggest that UTP sensitises a subpopulation of cutaneous C-fibre nociceptors via a previously undescribed G-protein-dependent potentiation of mechanically activated RA-type currents.

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