| First Author | Eijkelkamp N | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 1682 | PubMed ID | 23575686 |
| Mgi Jnum | J:205744 | Mgi Id | MGI:5546315 |
| Doi | 10.1038/ncomms2673 | Citation | Eijkelkamp N, et al. (2013) A role for Piezo2 in EPAC1-dependent mechanical allodynia. Nat Commun 4:1682 |
| abstractText | 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. |
