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.
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|Camilleri, Michael; Chang, Lin (2008) Challenges to the therapeutic pipeline for irritable bowel syndrome: end points and regulatory hurdles. Gastroenterology 135:1877-91|
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