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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-CFS (01))
Program Officer
Tonkins, William P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
Zip Code
Videlock, Elizabeth J; Shih, Wendy; Adeyemo, Mopelola et al. (2016) The effect of sex and irritable bowel syndrome on HPA axis response and peripheral glucocorticoid receptor expression. Psychoneuroendocrinology 69:67-76
Cheng, P; Shih, W; Alberto, M et al. (2013) Autonomic response to a visceral stressor is dysregulated in irritable bowel syndrome and correlates with duration of disease. Neurogastroenterol Motil 25:e650-9
Kim, S E; Chang, L (2012) Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms? Neurogastroenterol Motil 24:895-913
Chang, Lin (2011) The role of stress on physiologic responses and clinical symptoms in irritable bowel syndrome. Gastroenterology 140:761-5
Spiegel, Brennan M R; Farid, Mary; Esrailian, Eric et al. (2010) Is irritable bowel syndrome a diagnosis of exclusion?: a survey of primary care providers, gastroenterologists, and IBS experts. Am J Gastroenterol 105:848-58
Videlock, Elizabeth J; Adeyemo, Mopelola; Licudine, Arlene et al. (2009) Childhood trauma is associated with hypothalamic-pituitary-adrenal axis responsiveness in irritable bowel syndrome. Gastroenterology 137:1954-62
Chang, L; Sundaresh, S; Elliott, J et al. (2009) Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome. Neurogastroenterol Motil 21:149-59
Adeyemo, Mopelola A; Chang, Lin (2008) New treatments for irritable bowel syndrome in women. Womens Health (Lond Engl) 4:605-22;quiz 623
Spiegel, Brennan M R; Chey, William D; Chang, Lin (2008) Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors? Am J Gastroenterol 103:2972-6
Camilleri, Michael; Chang, Lin (2008) Challenges to the therapeutic pipeline for irritable bowel syndrome: end points and regulatory hurdles. Gastroenterology 135:1877-91

Showing the most recent 10 out of 18 publications