Based on clinical studies, women are more likely than men to experience a variety of chronic, recurrent visceral pain syndromes such as interstitial cystitis or irritable bowel syndrome (IBS). However, in contrast to well-characterized sex differences in animal models, experimental evidence to support gender differences in human pain perception remains inconclusive and mechanisms remain poorly understood. Potential mechanisms that may underlie gender-related differences in perception of visceral pain included fixed sexual dimorphism of brain regions concerned with central processing of noxious stimuli, and transient hormone-related cyclic modifiers of central pain processing. Since women are more likely than men to experience pain affecting pelvic viscera during copulation, pregnancy and labor, it is hypothesized that women exhibit differences in at least two type of responses to potential harmful sensations arising from the pelvic organs: altered activation of endogenous pain inhibition systems and altered attentional processes including hyper-vigilance. In the current proposal, the investigators will test the general hypothesis by determining gender-related differences in healthy control subjects and in IBS patients using H21502 PET imaging of the brain together with measurement of perceptual, autonomic, and neuroendocrine responses to noxious rectosigmoid stimulation. They will utilize two visceral stimulus paradigms based on previous work, one tests visceral sensitization from sigmoid colon conditioning and the other anticipatory responses to expected high and low intensity visceral sensation. This will allow for direct comparison of perceptual and sensory gender-related factors in IBS. The investigators will also separately examine stable, non-hormonal factors (in women on oral contraceptives) and hormonal factors (in ovulating women during the luteal and perimenstruation periods).

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
7R01NR004881-03
Application #
6186901
Study Section
Special Emphasis Panel (ZDE1-YS (16))
Program Officer
Hare, Martha L
Project Start
1998-09-15
Project End
2003-07-31
Budget Start
2000-08-23
Budget End
2003-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$231,913
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Berman, Steven M; Naliboff, Bruce D; Suyenobu, Brandall et al. (2008) Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome. J Neurosci 28:349-59
Labus, Jennifer S; Mayer, Emeran A; Chang, Lin et al. (2007) The central role of gastrointestinal-specific anxiety in irritable bowel syndrome: further validation of the visceral sensitivity index. Psychosom Med 69:89-98
Eisenberger, Naomi I; Jarcho, Johanna M; Lieberman, Matthew D et al. (2006) An experimental study of shared sensitivity to physical pain and social rejection. Pain 126:132-8
Berman, Steven M; Naliboff, Bruce D; Suyenobu, Brandall et al. (2006) Sex differences in regional brain response to aversive pelvic visceral stimuli. Am J Physiol Regul Integr Comp Physiol 291:R268-76
Naliboff, Bruce D; Berman, Steve; Suyenobu, Brandall et al. (2006) Longitudinal change in perceptual and brain activation response to visceral stimuli in irritable bowel syndrome patients. Gastroenterology 131:352-65
Mayer, Emeran A; Berman, Steven; Suyenobu, Brandall et al. (2005) Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis. Pain 115:398-409
Dickhaus, Britta; Mayer, Emeran A; Firooz, Nazanin et al. (2003) Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress. Am J Gastroenterol 98:135-43
Naliboff, Bruce D; Berman, Steve; Chang, Lin et al. (2003) Sex-related differences in IBS patients: central processing of visceral stimuli. Gastroenterology 124:1738-47
Berman, Steven M; Chang, Lin; Suyenobu, Brandall et al. (2002) Condition-specific deactivation of brain regions by 5-HT3 receptor antagonist Alosetron. Gastroenterology 123:969-77
Mayer, E A; Berman, S; Derbyshire, S W G et al. (2002) The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients. Aliment Pharmacol Ther 16:1357-66

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