Figure 1: Proposed mechanism of estradiol effect on ATP-induced (Ca2+)i signaling in primary sensory neurons. ATP acts on P2X3 receptor resulting in activation of the L-type voltage-gated calcium channel (VGCC) stimulating an increase in (Ca2+)i . Subsequent activation of voltage-gated sodium channels (VGSC) will lead to pain sensation. Capsaicin acting on nociceptive TRPV1 receptors directly induces (Ca2+)i . Both pathways are attenuated by membrane-associated estrogen receptor-α (ERα). ERα agonist 17β-estradiol attenuated increases P2X3 and TRPV1-mediated (Ca2+)i .
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