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A role for Piezo2 in EPAC1-dependent mechanical allodynia
dc.contributor.author | Eijkelkamp, N. | |
dc.contributor.author | Torres de Pinedo, Jesús Manuel | |
dc.date.accessioned | 2020-11-04T11:27:27Z | |
dc.date.available | 2020-11-04T11:27:27Z | |
dc.date.issued | 2013-04-09 | |
dc.identifier.citation | Eijkelkamp, N., Linley, J. E., Torres, J. M., Bee, L., Dickenson, A. H., Gringhuis, M., ... & Ishikawa, Y. (2013). A role for Piezo2 in EPAC1-dependent mechanical allodynia. Nature communications, 4(1), 1-13. [DOI: 10.1038/ncomms2673] | es_ES |
dc.identifier.uri | http://hdl.handle.net/10481/64046 | |
dc.description | N.E. and J.W. designed and supervised experiments. N.E. performed most of the in vivo and in vitro experiments. J.L. performed experiments to characterize hPiezo2. G.H and G.L. supervised by U.O., and J.T. and J.C. cloned hPiezo. L.B. performed the in vivo electrophysiology under the supervision of A.D. M.G. helped with the overexpression studies.M.M. performed surgery. Y.I. provided the Epac1 / mice. F.Z. provided the Epac constructs. N.E. and J.W. wrote manuscript with contributions of all authors. N.E., J.L. and L.B. contributed to data analysis and all authors contributed to the discussions | es_ES |
dc.description.abstract | Aberrant mechanosensation has an important role in different pain states. Here we show that Epac1 (cyclic AMP sensor) potentiation of Piezo2-mediated mechanotransduction contributes to mechanical allodynia. Dorsal root ganglia Epac1 mRNA levels increase during neuropathic pain, and nerve damage-induced allodynia is reduced in Epac1 / mice. The Epac-selective cAMP analogue 8-pCPT sensitizes mechanically evoked currents in sensory neurons. Human Piezo2 produces large mechanically gated currents that are enhanced by the activation of the cAMP-sensor Epac1 or cytosolic calcium but are unaffected by protein kinase C or protein kinase A and depend on the integrity of the cytoskeleton. In vivo, 8-pCPT induces long-lasting allodynia that is prevented by the knockdown of Epac1 and attenuated by mouse Piezo2 knockdown. Piezo2 knockdown also enhanced thresholds for light touch. Finally, 8-pCPT sensitizes responses to innocuous mechanical stimuli without changing the electrical excitability of sensory fibres. These data indicate that the Epac1–Piezo2 axis has a role in the development of mechanical allodynia during neuropathic pain. | es_ES |
dc.description.sponsorship | Netherlands Organization for Scientific Research (NWO) | es_ES |
dc.description.sponsorship | Jose Castillejo fellowship JC2010-0196 | es_ES |
dc.description.sponsorship | Spanish Government | es_ES |
dc.description.sponsorship | Medical Research Council UK (MRC) | es_ES |
dc.description.sponsorship | WCU at SNU R31-2008-000-10103-0 | es_ES |
dc.description.sponsorship | EU IMI Europain grant | es_ES |
dc.description.sponsorship | BBSRC LOLA grant | es_ES |
dc.description.sponsorship | Wellcome Trust | es_ES |
dc.description.sponsorship | Versus Arthritis 20200 | es_ES |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) BB/F000227/1 | es_ES |
dc.description.sponsorship | Medical Research Council UK (MRC) G0901905 G9717869 G1100340 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Protein-Kinase-C | es_ES |
dc.subject | Mechanosensitive Ion Channels | es_ES |
dc.subject | Sensory neurons | es_ES |
dc.subject | Intrathecal morphine | es_ES |
dc.subject | Inflammatory pain | es_ES |
dc.subject | Neurophatic pain | es_ES |
dc.subject | Cell adhesion | es_ES |
dc.subject | Epac proteins | es_ES |
dc.subject | Rat | es_ES |
dc.subject | Sensitization | es_ES |
dc.title | A role for Piezo2 in EPAC1-dependent mechanical allodynia | es_ES |
dc.type | journal article | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.identifier.doi | 10.1038/ncomms2673 | |
dc.type.hasVersion | VoR | es_ES |