The brain-gut axis in abdominal pain syndromes

Abstract

The importance of bidirectional brain-gut interactions in gastrointestinal (GI) illness is increasingly recognized, most prominently in the area of functional GI syndromes such as irritable bowel syndrome (IBS), functional dyspepsia, and functional chest pain. The brain receives a constant stream of interoceptive input from the GI tract, integrates this information with other interoceptive information from the body and with contextual information from the environment, and sends an integrated response back to various target cells within the GI tract. This system is optimized to assure homeostasis of the GI tract during physiological perturbations and to adapt GI function to the overall state of the organism. In health, the great majority of interoceptive information reaching the brain is not consciously perceived but serves primarily as input to autonomic reflex pathways. In patients with functional abdominal pain syndromes, conscious perception of interoceptive information from the GI tract, or recall of interoceptive memories of such input, can occur in the form of constant or recurrent discomfort or pain. This is often associated with alterations in autonomic nervous system output and with emotional changes. A model is proposed that incorporates reported peripheral and central abnormalities in patients with IBS, extrapolates similar alterations in brain-gut interactions to patients with other chronic abdominal pain syndromes, and provides novel treatment targets.

Figure 1

Hierarchical organization of homeostatic reflex systems within the brain-gut axis. (a) Homeostatic afferents that report the physiological condition of the GI tract terminate in lamina I of the dorsal horn (corresponding vagal afferent pathways are not shown). The ascending projections of these neurons provide the basis for autonomic reflex arcs at different levels of the brain-gut axis (enteric nervous system reflexes not shown). Limbic, paralimbic, and prefrontal centers provide modulatory influences on the gain of these reflexes. The interoceptive input into these reflexes is generally not consciously perceived except in situations that require an action (e.g., pain) or in pathological conditions. Modified with permission from Reference 82. (b) Cortical modulation of homeostatic afferent input to the central nervous system. Prefrontal regions modulate activity in limbic and paralimbic regions, subregions of the anterior cingulate cortex, and hypothalamus, which in turn regulate activity of descending inhibitory and facilitatory descending pathways through the periaqueductal gray and pontomedullary nuclei. Activity in these corticolimbic pontine networks mediates the effect of cognitions and emotions on the perception of homeostatic feelings, including visceral pain and discomfort. Abbreviations: ANS, autonomic nervous system; dlPFC, dorsolateral PFC; orbFC, orbitofrontal cortex; PAG, periaqueductal gray; RVM, rostroventral medulla; RVLM, rostroventrolateral medulla; VMM, ventromedial medulla; A6, locus coeruleus; Ins, insula; Hypoth, hypothalamus; Amy, amygdala; ACC, anterior cingulate cortex.

Figure 2

Multiple systems and brain networks involved in endogenous pain modulation (adapted with permission from Reference 16). For details, see text.

Figure 3

Bidirectional brain-visceral interactions. Interoceptive input is encoded by a network of transducers in the gut and conveyed to the brain vial vagal and spinal afferents, immune mediators, and endocrine signals. Signals from the intestinal microflora may also be transduced into interoceptive signals at the host-microbial interface. At the brain level, this interoceptive information is integrated with information about contextual factors, and appropriate responses reach the gut via the two branches of the autonomic nervous system and the hypothalamic pituitary axis (HPA). Prolonged dysregulation of these interactions may result in central and peripheral neuroplastic changes. Abbreviations: ACTH, adrenocorticotropic hormone; SNS, sympathetic nervous system; PSNS, parasympathetic nervous system; ICC, interstitial cell of Cajal; ECC, enterochromaffin cell. For details, see text. Modified from Reference 83 with permission.