Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal (GI) disorder characterized by abdominal pain and alterations in bowel pattern. IBS disproportionately affects women;10-15% of women are affected. IBS is challenging to patients and health care providers in that the mechanism(s) accounting for symptoms are not well understood and treatment options are not consistently effective. The disorder is associated with variable levels of distress ranging from episodic mild to severe and at times disruptive to work and school. In terms of annual health care dollars, IBS is ranked second behind GERD. The focus of our work to date has been to understand those biobehavioral, gender, and psychological distress factors linked to symptom type and severity. Intriguing results support the hypothesis that psycho-logical, physiological and target gene polymorphisms differences exist in IBS subgroups. Psychological distress, the autonomic nervous system and serotonin transporter protein polymorphisms may serve as biomarkers of symptom type and severity in women with IBS. Validation of these biomarkers in patients with IBS could lead to development of targeted, novel therapies for subgroups with IBS. In this competitive renewal (R01NR 0194) application we propose to test the primary hypothesis that the divergence in vagal tone is associated with visceral sensitivity. We will also assess the physiologic links between vagal tone and other indicators of central mechanisms (arousal [startle reflex], and descending noxious inhibitory control). Results will allow us to examine biomarkers within a common heterogeneous condition.
Specific aims : 1) Test the relationship between vagal tone and central arousal (startle reflex and diffuse noxious inhibitory control [DNIC]) in women with moderate to severe IBS;2) compare indicators of central arousal mechanisms (startle reflex, DNIC) and upper GI visceral hypersensitivity (water loading), in three groups: moderate to severe diarrhea-predominant IBS versus women with moderate to severe constipation-predominant IBS versus control women;3) test the relationship between vagal tone and rectal hypersensitivity in a subset of the women;4) explore the relationships of startle reactivity, DNIC , and upper GI visceral hypersensitivity with genotype (SERT, 12-ADR, COMT, BNDF), abdominal pain reports, childhood abuse history, health related quality of life, current stress, and current and history of psychological distress. Results will increase our understanding of the underlying mechanisms accounting for chronic symptom reports as well as to examine biomarkers within a common heterogeneous condition, IBS.

Public Health Relevance

This application will test the primary hypothesis that the divergence in vagal tone noted in prior work is associated with clinical indicators of visceral sensitivity and intestinal transit. This project will assess the physiologic links between vagal tone and other indicators of central mechanisms (i.e., arousal [startle reflex], and descending noxious inhibitory control). Results will lead to greater understanding of the underlying mechanisms accounting for chronic symptom reports as well as examine an endophenotype within a common heterogeneous condition, IBS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR001094-24
Application #
8401540
Study Section
Nursing Science: Adults and Older Adults Study Section (NSAA)
Program Officer
Tully, Lois
Project Start
1984-09-15
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2014-12-31
Support Year
24
Fiscal Year
2013
Total Cost
$414,962
Indirect Cost
$142,661
Name
University of Washington
Department
Other Health Professions
Type
Schools of Nursing
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Jun, Sang-Eun; Kohen, Ruth; Cain, Kevin C et al. (2014) TPH gene polymorphisms are associated with disease perception and quality of life in women with irritable bowel syndrome. Biol Res Nurs 16:95-104
Heitkemper, M M; Cain, K C; Deechakawan, W et al. (2012) Anticipation of public speaking and sleep and the hypothalamic-pituitary-adrenal axis in women with irritable bowel syndrome. Neurogastroenterol Motil 24:626-31, e270-1
Jun, S; Kohen, R; Cain, K C et al. (2011) Associations of tryptophan hydroxylase gene polymorphisms with irritable bowel syndrome. Neurogastroenterol Motil 23:233-9, e116
Heitkemper, Margaret M; Cain, Kevin C; Burr, Robert L et al. (2011) Is childhood abuse or neglect associated with symptom reports and physiological measures in women with irritable bowel syndrome? Biol Res Nurs 13:399-408
Park, Hyo Jung; Jarrett, Monica; Heitkemper, Margaret (2010) Quality of life and sugar and fiber intake in women with irritable bowel syndrome. West J Nurs Res 32:218-32
Ficca, Gianluca; Axelsson, John; Mollicone, Daniel J et al. (2010) Naps, cognition and performance. Sleep Med Rev 14:249-58
Vitiello, Michael V; Rybarczyk, Bruce; Von Korff, Michael et al. (2009) Cognitive behavioral therapy for insomnia improves sleep and decreases pain in older adults with co-morbid insomnia and osteoarthritis. J Clin Sleep Med 5:355-62
Burr, R L; Jarrett, M E; Cain, K C et al. (2009) Catecholamine and cortisol levels during sleep in women with irritable bowel syndrome. Neurogastroenterol Motil 21:1148-e97
Cain, Kevin C; Jarrett, Monica E; Burr, Robert L et al. (2009) Gender differences in gastrointestinal, psychological, and somatic symptoms in irritable bowel syndrome. Dig Dis Sci 54:1542-9
Kohen, Ruth; Jarrett, Monica E; Cain, Kevin C et al. (2009) The Serotonin Transporter Polymorphism rs25531 Is Associated with Irritable Bowel Syndrome. Dig Dis Sci :

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