Estrogen-dependent changes in visceral afferent sensitivity

Many forms of chronic pain are more prevalent in women and this is interpreted as the consequence of a direct role of estrogens in the modulation of pain perception. Some functional pain states, i.e. those without a clear and demonstrable pathology, are also more prevalent in women and the pain in these conditions is also modulated by hormonal variations during the menstrual cycle. Increased pain sensitivity is commonly interpreted as the consequence of peripheral or central hyperexcitability of nociceptive pathways. Therefore a role has been suggested for estrogen in the modulation of the excitability of nociceptive afferents and central neurons. The literature on the sign of this modulation is not uniform, with reports pointing to estrogen as either pro- or anti-nociceptive. In our hands, a permanent reduction in the levels of estrogen, such as that induced by surgical ovariectomy (OVX) generates a hyperalgesic state of slow onset and long duration that can be prevented or reversed by exogenous administration of estrogen. The hyperalgesia is characterized by mechanical and thermal hyperalgesia in the abdominal and pelvic regions as well as by visceral hypersensitivity. The possible role of estrogen in the prevention of chronic painful states is discussed.