FIGURE 4-4 The brain-gut axis and IBS. Relative prevalence of IBS according to severity, and relative contributions of peripheral (left side of triangle) and psychosocial (right side of triangle) factors to severity. Most patients have mild to moderate IBS symptoms with increased peripheral-nerve signaling. However, a smaller group of patients with moderate to severe symptoms also have impaired modulation of pain at the CNS level, which is enabled by psychosocial factors (such as trauma, abuse, life stress, psychosocial comorbidities, and poor coping). These patients experience increased symptoms at the level of the CNS signaling. Factors that may contribute to CNS signaling include life stress and abuse.

Activation of IBS symptoms results from physiologic dysfunction that occurs peripherally (for example, motility disturbances or intestinal infection with inflammation). The peripheral stimuli send signals from the colon up the spinal cord to the thalamus and then to the brain via two pathways. The brain regions innervated by those pathways, which are activated in response to painful colorectal stimuli, include the somatosensory cortex—the area responsible for localization and intensity of peripheral sensations—and the limbic system, including the thalamus, insula, amygdala, and anterior cingulate cortex, which is linked to emotional stress and cognitive interpretation of pain. The brain has the ability to turn down the incoming signals through descending inhibitory pathways that modulate pain transmission and incoming signals are thus downregulated at the level of the spinal cord. As discussed earlier, CRH secretion and the HPA axis can also regulate inflammation, including that of the bowel mucosa. In IBS, however, the normal regulatory mechanisms of the brain-gut axis are dysfunctional, and there is impaired regulation of visceral pain (Naliboff et al. 2001) and altered HPA reactivity. The latter disrupts normal control of mucosal immune function that results in inflammation via cytokine activation (Dinan et al. 2006). With brain imaging, it can be shown that psychosocial difficulties (such as anxiety and life stress, including abuse or trauma, hypervigilance, and maladaptive coping) can impair those regulatory mechanisms (Drossman 2005). The presence and intensity of



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