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Fig. 5 | Molecular Pain

Fig. 5

From: Contribution of Piezo2 to endothelium-dependent pain

Fig. 5

Schematic of vascular endothelial cell/Piezo2-dependent mechanism of innocuous stimulus induced enhancement of endothelin-1 hyperalgesia. Endothelin-1 activates ET receptors in the nociceptor terminal, sensitizing it to mechanical stimuli (hyperalgesia), detected as increased response to a noxious stimulus. The activation of ET receptors also sensitizes the endothelial cell to innocuous mechanical stimulation, inducing the release of ATP, which, in turn, act at P2X2/3 receptors on the nociceptor, producing enhancement of the endothelin-1-induced hyperalgesia (stimulus-dependent hyperalgesia). The insert represents the mechanical hyperalgesia induced by endothelin-1, acting on the nociceptor (darker gray box), and the increase in its magnitude after each stimulation (open arrows), due to a mechanism triggered by endothelin-1 at the endothelial cell (lighter gray box) involving Piezo2—which detects the innocuous mechanical stimulus—and the release of ATP

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