• 主页
  • 查找结果
  • Vascular endothelial cells mediate mechanical stimulation-induced enhancement of endothelin hyperalgesia via activation of P2X2/3 receptors on nociceptors.

Vascular endothelial cells mediate mechanical stimulation-induced enhancement of endothelin hyperalgesia via activation of P2X2/3 receptors on nociceptors.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2013-02-15)
Elizabeth K Joseph, Paul G Green, Oliver Bogen, Pedro Alvarez, Jon D Levine
摘要

Endothelin-1 (ET-1) is unique among a broad range of hyperalgesic agents in that it induces hyperalgesia in rats that is markedly enhanced by repeated mechanical stimulation at the site of administration. Antagonists to the ET-1 receptors, ET(A) and ET(B), attenuated both initial as well as stimulation-induced enhancement of hyperalgesia (SIEH) by endothelin. However, administering antisense oligodeoxynucleotide to attenuate ET(A) receptor expression on nociceptors attenuated ET-1 hyperalgesia but had no effect on SIEH, suggesting that this is mediated via a non-neuronal cell. Because vascular endothelial cells are both stretch sensitive and express ET(A) and ET(B) receptors, we tested the hypothesis that SIEH is dependent on endothelial cells by impairing vascular endothelial function with octoxynol-9 administration; this procedure eliminated SIEH without attenuating ET-1 hyperalgesia. A role for protein kinase Cε (PKCε), a second messenger implicated in the induction and maintenance of chronic pain, was explored. Intrathecal antisense for PKCε did not inhibit either ET-1 hyperalgesia or SIEH, suggesting no role for neuronal PKCε; however, administration of a PKCε inhibitor at the site of testing selectively attenuated SIEH. Compatible with endothelial cells releasing ATP in response to mechanical stimulation, P2X(2/3) receptor antagonists eliminated SIEH. The endothelium also appears to contribute to hyperalgesia in two ergonomic pain models (eccentric exercise and hindlimb vibration) and in a model of endometriosis. We propose that SIEH is produced by an effect of ET-1 on vascular endothelial cells, sensitizing its release of ATP in response to mechanical stimulation; ATP in turn acts at the nociceptor P2X(2/3) receptor.

材料
货号
品牌
产品描述

Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Triton X-100, for molecular biology
Sigma-Aldrich
Triton X-100, BioXtra
Sigma-Aldrich
Triton X-100 溶液, BioUltra, for molecular biology, ~10% in H2O
Sigma-Aldrich
Triton X-45
Sigma-Aldrich
Triton X-102
Sigma-Aldrich
Triton X-305 溶液, 70% in H2O
Sigma-Aldrich
Triton X-100, peroxide- and carbonyl-free
聚乙二醇单辛基苯基醚, European Pharmacopoeia (EP) Reference Standard