A large body of literature supports the idea that estrogen modulates nociceptive responses in pelvic pain syndromes; however, whether this hormone is pro- or anti-nociceptive remains unresolved. The dorsal root ganglion (DRG) is an important site of visceral afferent convergence and cross-sensitization. Within the context of our hypothesis visceral nociception and nociceptor sensitization appear to be regulated by purinergic P2X₃ and vanilloid TRPV1 receptors and 17β-estradiol modulates DRG neuron response to ATP (P2X agonist) and capsaicin (TRPV1 agonist) suggesting that visceral afferent nociceptors are modulated by estrogen in the DRG. 17-β estradiol (E2), the most common form of estrogen, acts on functional properties of P2X₃ and TRPV1 receptors in DRG neurons in vitro. The localization of estrogen receptors (ER) in DRG neurons and the attenuation of ATP/capsaicin-induced intracellular calcium concentration [Ca²⁺]_i strongly suggest that E2 modulates visceral pain processing peripherally. Moreover, E2 appears to have different actions on nociceptive signaling depending on the input.  Based on our data we propose that E2 can gate primary afferent response to increase or decrease nociception.