The first clinical observation of brain-gut interactions dates back to Beaumont's classical monograph published in 1833 that detailed alterations of gastric mucosa in relation with the mental state of his fistulous subject, Alexis St. Martin (1). Seminal reports by Cannon at the beginning of the last century brought experimental proof of the impact of emotion (fear, rage, and hunger) on gastric secretory and motor function in cats (2). However, Selye deserves much of the credit for introducing the term "stress" which he defined as '' the adaptive bodily changes to any demands'' (3). In his 1936 landmark publication, he identified the gut, immune systems, and endocrine systems as primary targets altered by various physical and chemical challenges (4). Since then, over 200,000 articles are listed in PubMed related to stress and cell or body responses. However, the impact of stress on visceral pain has emerged only recently, largely driven by the early clinical recognition that stressful events exacerbate or even trigger abdominal pain episodes in nearly half of patients with irritable bowel syndrome (IBS) (5) and increase pain response to colorectal distension (CRD) (6,7). Now growing clinical reports document that the manifestations of IBS symptoms, including visceral pain, are modulated by stress (8-10) and that disorders of the brain-gut axis are part of the underlying mechanisms involved in visceral hypersensitivity in IBS patients (11-13). Recently, several laboratories have developed experimental models of visceral pain that recapture some features of IBS symptoms to gain insight into the pathophysiology of this functional bowel disorder.

This chapter will focus on the modulatory effects of stress on visceral pain induced by CRD in experimental animals and aspects of sex differences. Mechanisms of stress-related visceral hyperalgesia will be mainly addressed in the context of activation of brain corticotro-pin-releasing factor (CRF) and CRF receptors. This brain-signaling pathway has emerged to intimately connect the stress responses (14), including alterations of lower gut function (15) and the development of diseases (16).

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How to Deal with Stress and Cope in the 21st Century

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