Mechanisms of hypersensitivity in IBS and functional disorders

Abstract

General introductionThe concept of visceral hypersensitivity is accepted as being germane to several functional gastrointestinal disorders (FGIDs). The causes or risk factors associated with this hypersensitivity are unclear. This article addresses the proposed mechanisms leading to hypersensitivity: from genetic to inflammatory disorders, from central to peripheral alterations of function. However, in order to place visceral hypersensitivity in a more global perspective as an aetiological factor for FGIDs, it also provides a review of recent evidence regarding the role of other peripheral mechanisms (the intraluminal milieu), as also genetic factors in the pathophysiology of these disorders. The article has been divided into five independent sections. The first three sections summarize the evidence of visceral hypersensitivity as a biological marker of functional gut disorders, the peripheral and central mechanisms involved, and the role of inflammation on hypersensitivity. In opposition to visceral hypersensitivity as an isolated phenomenon in functional gut disorders, the last two sections focus on the importance of peripheral mechanisms, like motor disturbances, specifically those resulting on altered transport of intestinal gas, and alterations of the intraluminal milieu and genetics.Keywords abdominal pain, functional gut disorders, irritable bowel syndrome, visceral hypersensitivity. VISCERAL HYPERSENSITIVITY: BIOLOGICAL MARKER, PERIPHERAL MECHANISMS AND HETEROGENEITY IntroductionVisceral hypersensitivity is currently the leading hypothesis to explain irritable bowel syndrome (IBS) and other functional gastrointestinal disorders (FGIDs). After years of disappointing research trying to establish a correlation between the increased motor activity of the gut and the painful cramps felt by IBS patients, the theory that pain could be related to enhanced visceral sensitivity was raised. Ritchie, 1 in 1973, first reported that IBS patients were more sensitive than normal subjects to balloon distension of the colon. This observation of increased visceral sensitivity in IBS patients was confirmed by many researchers including Whitehead et al. 2 , Mertz et al. 3 and others. In agreement with the hypersensitivity of the colon found in IBS patients, intolerance to gastric distension was also documented in patients with functional dyspepsia (FD). 4-6Visceral hypersensitivity: biological marker of FGID?Mertz et al. 3 proposed that Ôaltered rectal perception is a biological marker of patients with IBSÕ as it was identified in 94 of 100 IBS patients studied by a rectal distension by barostat. We collected rectal distension data by an electronic barostat in 164 patients (86 IBS, 26 painless constipation, 21 FD and 31 others with miscellaneous conditions), 7 as also in 25 normal controls evaluated. As expected ( thresholds to rectal distension were lower in patients with IBS when compared with control subjects; they were also lower than in patients with painless constipation, FD or other miscellaneous conditions. Assuming ...

Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats

“…RECURRENT ABDOMINAL PAIN ASSOCIATED with altered bowel habits and increased perception of physiological and experimental colonic stimuli (visceral hypersensitivity) are characteristic findings in patients with irritable bowel syndrome (IBS) (4). Although the pathophysiological basis of IBS is incompletely understood, epidemiological and experimental data indicate an important role of altered brain-gut interactions in this disorder.…”

TRP Channels in Visceral Pain

“…Allodynia and hyperalgesia to mechanical events like distension and contraction are hallmarks of chronic visceral pains [88][89][90], along with inflammation, which may be very low-grade histologically [91][92][93]. Therefore, it is clear that therapies are needed that reduce signalling of nociceptive mechanosensory and inflammatory events.…”

Visceral Hypersensitivity and Altered Colonic Motility in Type 2 Diabetic Rat

“…Alternatively, considering that chronic diabetic neuropathy often leads to loss of sensation, one could also postulate that the normo-sensitive diabetic rats might have developed severer diabetic neuropathy that counteracted sensory neuronal sensitization by STZ. It is also noteworthy that stress and low-grade gut inflammation are considered to trigger visceral pain in functional GI disorder such as irritable bowel syndrome, 24,25 suggesting the stress response and gut inflammatory states in the hypersensitive diabetic rats could differ from those in their normo-sensitive counterpart.…”