Peripheral sensitisation of nociceptors via G-protein-dependent potentiation of mechanotransduction currents.
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.
Lechner
Stefan G
SG
Department of Neuroscience, Max-Delbrück-Center for Molecular Medicine, Robert Rössle Str. 10, 3125 Berlin, Germany.
Lewin
Gary R
GR
D000255:Adenosine Triphosphate / Q000008:administration & dosage; D000818:Animals; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000187:drug effects / Q000294:innervation*; D012879:Skin Physiological Phenomena; D014544:Uridine Triphosphate / Q000008:administration & dosage
D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D014544:Uridine Triphosphate