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2015 ; 11
(ä): 65
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Contribution of Piezo2 to endothelium-dependent pain
#MMPMID26497944
Ferrari LF
; Bogen O
; Green P
; Levine JD
Mol Pain
2015[Oct]; 11
(ä): 65
PMID26497944
show ga
BACKGROUND: We evaluated the role of a mechanically-gated ion channel, Piezo2, in
mechanical stimulation-induced enhancement of hyperalgesia produced by the
pronociceptive vasoactive mediator endothelin-1, an innocuous mechanical
stimulus-induced enhancement of hyperalgesia that is vascular endothelial cell
dependent. We also evaluated its role in a preclinical model of a vascular
endothelial cell dependent painful peripheral neuropathy. RESULTS: The local
administration of oligodeoxynucleotides antisense to Piezo2 mRNA, at the site of
nociceptive testing in the rat's hind paw, but not intrathecally at the central
terminal of the nociceptor, prevented innocuous stimulus-induced enhancement of
hyperalgesia produced by endothelin-1 (100 ng). The mechanical hyperalgesia
induced by oxaliplatin (2 mg/kg. i.v.), which was inhibited by impairing
endothelial cell function, was similarly attenuated by local injection of the
Piezo2 antisense. Polymerase chain reaction analysis demonstrated for the first
time the presence of Piezo2 mRNA in endothelial cells. CONCLUSIONS: These results
support the hypothesis that Piezo2 is a mechano-transducer in the endothelial
cell where it contributes to stimulus-dependent hyperalgesia, and a model of
chemotherapy-induced painful peripheral neuropathy.
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