Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

Abstract

Background: Irritable bowel syndrome and other gastrointestinal (GI) and non-GI disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint disorder, interstitial cystitis/painful bladder syndrome, and chronic fatigue syndrome are known as functional pain syndromes. They commonly coexist within the same individual. The pathophysiologic mechanisms of these disorders are not well understood, but it has been hypothesized that they share a common pathogenesis.

Purpose: The objective of this review is to discuss the proposed pathophysiologic mechanisms, which have been similarly studied in these conditions. These mechanisms include enhanced pain perception, altered regional brain activation, infectious etiologies, dysregulations in immune and neuroendocrine function, and genetic susceptibility. Studies suggest that these functional disorders are multifactorial, but factors which increase the vulnerability of developing these conditions are shared.

Figure 1

Factors that increase the vulnerability of developing irritable bowel syndrome (IBS) or trigger symptom onset include psychosocial symptoms, genetic factors, and infection. The physiological effects of psychological and physical stressors on gut function and brain–gut interactions are mediated by outputs of the autonomic, neuroendocrine, and pain modulatory responses. Patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility and secretion and in alterations in the perception of visceral events. Pathophysiologic mechanisms reported in IBS include alterations in central processing and modulation of sensory input, autonomic and neuroendocrine responses, and gut-related factors. Functional brain imaging techniques are beginning to identify brain circuits involved in the perceptual alterations. Adapted from. This figure has been reproduced with permission of the International Association for the Study of Pain ® (IASP ®). The figure may not be reproduced for any other purpose without permission.

Figure 2

Peripheral and central influences on severity of functional pain syndromes. This figure depicts multiple factors which may contribute to pain symptoms in functional pain syndromes. Afferent excitation and thus upregulation of afferent pathways may be observed in patients with mild to moderate symptoms with contributory factors being diet, infection, injury, hormones, and peptides. Moderate to severe symptoms may be due to disinhibition at the level of central modulation of pain leading to a lack of inhibitory effects at the peripheral afferent level. Contributory factors associated with increasing severity include life stressors, greater psychosocial disturbances, poor coping skills, and abuse. Concurrently, there is an increase in symptom reporting. Adapted from. This figure has been reproduced with permission of the International Association for the Study of Pain ® (IASP ®). The figure may not be reproduced for any other purpose without permission.