As a competitive renewal application, this study builds on the previously funded study focusing on testing of a neurobiological model relevant to patients with FM and IBS to explain the wide range of symptoms within each patient population, and the overlap of symptoms between the two groups. This model postulates stress-induced alterations in central nervous system (CNS)circuits, referred to as the emotional motor ystem resulting in inadequate antinociceptive response, altered autonomic (e.g., sympathetic nervous lystem, SNS)and hypothalamic-pituitary-adrenal (HPA)axis responses. The goal of the current proposal is to focus on the role of enhanced pain amplification mechanisms of heightened attention and symptom- specific anxiety in IBS and FM. In the current proposal, we hypothesize that IBS and FM patients have developed symptom-specific anxiety from previously threatening visceral and somatic stimuli, respectively, which amplifies pain-related symptoms. Based on previous studies, anxiety-related amplification of pain can be explained by an altered responsiveness of the extended amygdala (amygdala and bed nucleus of stria terminalis) which has been implicated in anxiety-related responses as well as pain modulation and stress hormone responses. The extended amygdala is the primary site that mediates both the anxiety-enhanced startle response (ASPR) and the corticotropin-releasing factor (CRF)-enhanced startle response. We hypothesize that APSR and HPA axis levels will be enhanced in patients with IBS or FM compared to healthy controls, but specifically in response to a visceral threat in IBS patients and a somatic threat in FM patients.
Our specific aims are: 1) To determine if APSR is enhanced to a visceral threat in IBS and to a somatic threat in FM compared to controls, and if they are related to self-reported symptom-specific anxiety; 2) To determine if IBS and FM patients have perceptual hypersensitivity to visceral and somatic stimuli, respectively, and if it is related to APSR;3) To determine if APSR is related to HPA axis and noradrenergic responses to the visceral and somatic threat conditions in IBS and FM, respectively;and 4) To determine if APSR is related to alterations in central stress mediators measured during a somatic and visceral threat condition in IBS and FM.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR046122-10
Application #
7761734
Study Section
Special Emphasis Panel (ZRG1-CFS (01))
Program Officer
Tonkins, William P
Project Start
1999-09-13
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2012-01-31
Support Year
10
Fiscal Year
2010
Total Cost
$261,136
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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