@misc{10481/64046,
year = {2013},
month = {4},
url = {http://hdl.handle.net/10481/64046},
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.},
organization = {Netherlands Organization for Scientific Research (NWO)},
organization = {Jose Castillejo fellowship 	
JC2010-0196},
organization = {Spanish Government},
organization = {Medical Research Council UK (MRC)},
organization = {WCU at SNU 	
R31-2008-000-10103-0},
organization = {EU IMI Europain grant},
organization = {BBSRC LOLA grant},
organization = {Wellcome Trust},
organization = {Versus Arthritis

20200},
organization = {Biotechnology and Biological Sciences Research Council (BBSRC)

BB/F000227/1},
organization = {Medical Research Council UK (MRC)

G0901905
G9717869
G1100340},
publisher = {Nature Publishing Group},
keywords = {Protein-Kinase-C},
keywords = {Mechanosensitive Ion Channels},
keywords = {Sensory neurons},
keywords = {Intrathecal morphine},
keywords = {Inflammatory pain},
keywords = {Neurophatic pain},
keywords = {Cell adhesion},
keywords = {Epac proteins},
keywords = {Rat},
keywords = {Sensitization},
title = {A role for Piezo2 in EPAC1-dependent mechanical allodynia},
doi = {10.1038/ncomms2673},
author = {Eijkelkamp, N. and Torres de Pinedo, Jesús Manuel},
}