Abstract
Clinical studies suggest the comorbidity of functional pain syndromes such as irritable bowel syndrome, painful bladder syndrome, chronic pelvic pain, and somatoform disorders approaches 40% to 60%. The incidence of episodic or persistent visceral pain associated with these “functional” disorders is two to three times higher in women than in men. One of the possible explanations for this phenomenon is estrogen modulation of viscerovisceral cross-sensitization. While a central site of this modulation has been shown previously, our studies suggest a peripheral site, the dorsal root ganglion (DRG). Estrogens have remarkably wide range of functions including modulation of voltage-gated calcium channels (VGCCs) and purinoreceptors (P2Xs). Significantly, inflammation dramatically alters purinoception by causing a several fold increase in ATP-activated current, alters the voltage dependence of P2X receptors, and enhances the expression of P2X receptors increasing neuronal hypersensitivity. Gonadal hormones are thought as indispensable cornerstones of the normal development and function, but it appears that no body region, no neuronal circuit, and virtually no cell is unaffected by them. Thus, increasing awareness toward estrogens appears to be obligatory.
Highlights
Clinical studies suggest the comorbidity of functional pain syndromes such as irritable bowel syndrome, painful bladder syndrome, chronic pelvic pain, and somatoform disorders approaches 40% to 60%
While a central site of this modulation has been shown previously, our studies suggest a peripheral site, the dorsal root ganglion (DRG)
Visceral afferents are sensitive to Adenosine -triphosphate (ATP) [3], and several indirect pieces of evidence suggest that visceral afferents are E2-sensitive: (i) visceral pain is affected by hormonal level in cycling females [4]; (ii) there are gender differences in the prevalence of functional disorders involving the viscera [5]; (iii) putative visceral afferents [6] fit into the population of DRG neurons that are E2-sensitive
Summary
Sex hormones and 17β-estradiol (E2), in particular, directly influence the functions of primary afferent neurons. It is generally accepted that each primary afferent neuron is a single sensory channel, several studies have challenged that view and demonstrate that a population of DRG neuron can innervate both the viscera and somatic tissues. The inflammation in the reproductive tract can cross-sensitize the response to ATP in colonic DRGs. it has been accepted that each primary afferent neuron is a single sensory channel (Figure 1(a)), several studies has challenged that view [9], and our own data using retrograde labeling demonstrate that population of DRG receive sensory input from different visceral organs: uterus and colon [10] and that inflammation in the uterus upregulated nociceptive signaling in the colon [11] (Figure 1(b))
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