Anxiety Disorders: Bradesi S

Mayer EA, Tillisch K, Bradesi S. · Department of Medicine, Center for Neurovisceral Sciences and Women's Health, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA. · Aliment Pharmacol Ther. · Pubmed #16948804 No free full text.

Abstract: BACKGROUND: The importance of bi-directional brain-gut interactions in gastrointestinal illness is increasingly being recognized, most prominently in the area of functional gastrointestinal disorders. Numerous current and emerging therapies aimed at normalizing brain-gut interactions are a focus of interest, particularly for irritable bowel syndrome and functional dyspepsia. METHODS: A literature search was completed for preclinical and clinical studies related to central modulation of gastrointestinal functions and published in English between 1980 and 2006. RESULTS: Existing data, while sparse, support the use of different classes of antidepressant drugs, including tricyclics, and selective and non-selective serotonin reuptake inhibitors in irritable bowel syndrome. Serotonin receptor agonists and antagonists with peripheral and possibly central effects are effective in treating specific subtypes of irritable bowel syndrome. Based largely on theoretical and preclinical evidence, several novel compounds that selectively target receptors at multiple levels within the brain-gut axis such as neurokinin, somatostatin and corticotropin-releasing factor receptor antagonists are promising. CONCLUSIONS: This review discusses the rationale for modulation of the brain-gut axis in the treatment of functional gastrointestinal disorders and highlights the most promising current and future therapeutic strategies.

Bradesi S, Schwetz I, Ennes HS, Lamy CM, Ohning G, Fanselow M, Pothoulakis C, McRoberts JA, Mayer EA. · Department of Medicine, Center for Neurovisceral Sciences and Women's Health, David Geffen School of Medicine at University of California, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California 90073, USA. · Am J Physiol Gastrointest Liver Physiol. · Pubmed #15746211 links to  free full text

Abstract: Chronic stress plays an important role in the development and exacerbation of symptoms in functional gastrointestinal disorders. To better understand the mechanisms underlying this relationship, we aimed to characterize changes in visceral and somatic nociception, colonic motility, anxiety-related behavior, and mucosal immune activation in rats exposed to 10 days of chronic psychological stress. Male Wistar rats were submitted daily to either 1-h water avoidance (WA) stress or sham WA for 10 consecutive days. The visceromotor response to colorectal distension, thermal somatic nociception, and behavioral responses to an open field test were measured at baseline and after chronic WA. Fecal pellets were counted after each WA stress or sham WA session as a measure of stress-induced colonic motility. Colonic samples were collected from both groups and evaluated for structural changes and neutrophil infiltration, mast cell number by immunohistochemistry, and cytokine expression by quantitative RT-PCR. Rats exposed to chronic WA (but not sham stress) developed persistent visceral hyperalgesia, whereas only transient changes in somatic nociception were observed. Chronically stressed rats also exhibited anxiety-like behaviors, enhanced fecal pellet excretion, and small but significant increases in the mast cell numbers and the expression of IL-1beta and IFN-gamma. Visceral hyperalgesia following chronic stress persisted for at least a month. Chronic psychological stress in rats results in a robust and long-lasting alteration of visceral, but not somatic nociception. Visceral hyperalgesia is associated with other behavioral manifestations of stress sensitization but was only associated with minor colonic immune activation arguing against a primary role of mucosal immune activation in the maintenance of this phenomenon.