Estrogen modulation of visceral nociception

Abstract

The incidence of persistent, episodic, or chronic visceral pain disorders such as irritable bowel syndrome and other functional syndromes (fibromyalgia, interstitial cystitis, chronic pelvic pain and others) are more prevalent in females. Defining the site(s) and mechanisms through which sex steroid hormones modulate visceral nociception is an important step in understanding the gender differences in pain perception. One such mechanism may be the convergence of nociceptive stimuli and estrogen input on the primary afferent neurons, which innervate viscera. In our study we determined how estrogen interferes with pain transmission at the level of primary sensory neurons. Based on our results, it is likely that estrogen receptors expressed in primary afferent neurons located in the dorsal root ganglion modulate purinergic and opiate receptors-mediating chemical signaling associated with nociception. Nociception is a balance of pro- and anti-nociceptive inputs that is subject to regulation depending on the state of the organism. The modulation of purinergic receptor- mediated increase in intracellular calcium concentration and attenuation of opioid receptors functions by estrogen observed in primary afferent neurons strongly suggest that estrogen modulates visceral pain processing peripherally. Moreover, estrogen appears to have different actions on nociceptive signaling depending on the input acting as anti-nociceptive by inhibiting purinergic receptors-mediating response but also interferes with anti-nociceptive actions of opioids. © 2008 Springer Netherlands.