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


  • S.G. Lechner
  • G.R. Lewin


  • Journal of Physiology


  • J Physiol 587 (Pt 14): 3493-3503


  • 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 ionchannels. Here we show that the algogens UTP and ATP potentiate mechanosensitive RA-currents in peptidergic nociceptive DRG neurons and reduce thresholds formechanically induced action potential firing in these neurones. Pharmacological characterisation suggests that this effect is mediated by the Gq-coupled P2Y2 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.