Departments of Medicine, Psychiatry and Biobehavioral Sciences, CNS: Center for Neurovisceral Sciences and Women's Health, UCLA Division of Digestive Diseases, UCLA and VA GLAHS, WLA VA Medical Center, Los Angeles, CA 90073, USA.
Recent interest has focused on sex-related differences in irritable bowel syndrome (IBS) physiology and treatment responsiveness to novel pharmacologic therapies. Similar to a variety of other chronic pain conditions and certain affective disorders, IBS is more prevalent amongst women, both in population-based studies as well as in clinic-based surveys. Non-painful gastrointestinal symptoms, constipation and somatic discomfort are more commonly reported by female IBS patients. While perceptual differences to rectosigmoid stimulation are only observed following repeated noxious stimulation of the gut, sex-related differences in certain sympathetic nervous system (SNS) responses to rectosigmoid stimulation are consistently seen. Consistent with experimental findings in animals, current evidence is consistent with a pathophysiological model which emphasizes sex-related differences in autonomic and antinociceptive responses to certain visceral stimuli.
"It is also found that male IBS patients had significantly higher sympathovagal balance than healthy male controls, whereas no differences were noted between IBS females and female controls. However, differences in autonomic nervous system responses to specific stimuli may also play a role in producing sex-based variations in IBS symptom patterns and in differential responses to some pharmacological agents . "
[Show abstract][Hide abstract] ABSTRACT: Irritable Bowel Syndrome (IBS) represents a functional disorder of gastrointestinal tract without the presence of an anatomic defect, in which abdominal pain is relieved with defecation and is associated with altered bowel habits.IBS includes a wide range of symptoms while its pathophysiology is very complicated. Recent studies indicate that the most important mechanisms include visceral sensitivity, abnormal gut motility and autonomous nervous system dysfunction. The interactions between these three mechanisms make bowel's function susceptible to many exogenous and endogenous factors like gastrointestinal flora, feeding and psychosocial factors. Recent data indicate that according to the above mechanisms, the influence of genetic factors and polymorphisms of human DNA in the development of IBS is equally important.
Gut Pathogens 05/2010; 2(1):3. DOI:10.1186/1757-4749-2-3 · 2.28 Impact Factor
"Like many other syndromes characterized by chronic physical or emotional pain and discomfort, IBS is significantly more common in women (Chang and Heitkemper, 2002) and sex-related differences in the perceptual and emotional responses of IBS patients to aversive visceral stimuli have been reported (Chang et al., 2006b; Heitkemper et al., 2003; Mayer et al., 2004; Tillisch et al., 2005). Greater subjective responses in female IBS patients may be related to sex differences in brain responses to visceral stimuli (Berman et al., www.elsevier.com/locate/ynimg "
[Show abstract][Hide abstract] ABSTRACT: Differences in brain responses to aversive visceral stimuli may underlie previously reported sex differences in symptoms as well as perceptual and emotional responses to such stimuli in patients with irritable bowel syndrome (IBS). The goal of the current study was to identify brain networks activated by expected and delivered aversive visceral stimuli in male and female patients with chronic abdominal pain, and to test for sex differences in the effective connectivity of the circuitry comprising these networks. Network analysis was applied to assess the brain response of 46 IBS patients (22 men and 24 women) recorded using [15O] water positron emission tomography during rest/baseline and expected and delivered aversive rectal distension. Functional connectivity results from partial least squares analyses provided support for the hypothesized involvement of 3 networks corresponding to: 1) visceral afferent information processing (thalamus, insula and dorsal anterior cingulate cortex, orbital frontal cortex), 2) emotional-arousal (amygdala, rostral and subgenual cingulate regions, and locus coeruleus complex) and 3) cortical modulation (frontal and parietal cortices). Effective connectivity results obtained via structural equation modeling indicated that sex-related differences in brain response are largely due to alterations in the effective connectivity of emotional-arousal circuitry rather than visceral afferent processing circuits. Sex differences in the cortico-limbic circuitry involved in emotional-arousal, pain facilitation and autonomic responses may underlie the observed differences in symptoms, and in perceptual and emotional responses to aversive visceral stimuli.
"Pain arising from visceral organs is one of the most common forms of pain in the clinical setting, and one of the most frequent reasons why patients seek medical attention (Cervero and Laird 1999). In general, women are more sensitive to pain than men and functional bowel disorders, such as irritable bowel syndrome (IBS) are 2–3 times more prevalent in women (Berkley 1997;Heitkemper and Jarrett 2001;Mayer et al. 2004). The severity of pain symptoms in women with IBS fluctuates with the menstrual cycle suggesting female gonadal hormone (s) modulate pain processing (Houghton et al. 2002;Palomba et al. 2005). "
[Show abstract][Hide abstract] ABSTRACT: Pain symptoms in several chronic pain disorders in women, including irritable bowel syndrome, fluctuate with the menstrual cycle suggesting a gonadal hormone component. In female rats, estrogens modulate visceral sensitivity although the underlying mechanism(s) are unknown. In the present study the effects of 17-beta estradiol on N-methyl-D-aspartate (NMDA) receptor signaling of colorectal nociceptive processing in the spinal cord were examined. Estrogen receptor alpha and the NR1 subunit of the NMDA receptor are co-expressed in dorsal horn neurons, supporting a direct action of estradiol on NMDA receptors. Intrathecal administration of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (APV) dose-dependently attenuated the visceromotor response with greater potency in ovariectomized (OVx) rats compared to OVx with estradiol replacement (E2) rats. Estradiol significantly increased protein expression of NR1 in the lumbosacral spinal cord compared to OVx rats. Colorectal distention significantly increased phosphorylation of NR1ser-897, a PKA phosphorylation site on the NR1 subunit in E2, but not OVx rats. Intrathecal administration of a PKA inhibitor significantly attenuated the visceromotor response, decreased NR1 phosphorylation and increased the potency of APV to attenuate the visceromotor response compared to vehicle-treated E2 rats. These data suggest that estradiol increases spinal processing of visceral nociception by increasing NMDA receptor NR1 subunit expression and increasing site-specific receptor phosphorylation on the NR1 subunit contributing to an increase in NMDA receptor activity.
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