'First-in-man': characterising the mechanosensitivity of human colonic afferents

Jiang, Weiwei; Adam, I. J.; Kitsanta, Panagiota; Tiernan, James; Hill, Chris; Shorthouse, A. J.; Grundy, David

doi:10.1136/gut.2010.229799

Cited by 28 publications

(30 citation statements)

References 5 publications

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“…Th e development and characterization of animal models of visceral hypersensitivity are clearly valuable in understanding how symptoms develop and persist, but as yet no animal model concurrently demonstrates all the symptoms of IBS. Little is known about changes in the peripheral nervous system in IBS patients, mainly due to the diffi culty in accessing visceral neuronal tissue in humans; however, there have been recent promising studies characterizing human GI nerve functions ( 54,119,120 ).…”

Section: Discussionmentioning

confidence: 99%

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

129

117

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Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterized by pain or discomfort from the lower abdominal region, which is associated with altered bowel habit. Despite its prevalence, there is currently a lack of effective treatment options for patients. IBS has long been considered as a neurological condition resulting from alterations in the brain gut axis, but immunological alterations are increasingly reported in IBS patients, consistent with the hypothesis that there is a chronic, but low-grade, immune activation. Mediators released by immune cells act to either dampen or amplify the activity of GI nerves. Release of a number of these mediators correlates with symptoms of IBS, highlighting the importance of interactions between the immune and the nervous systems. Investigation of the role of microbiota in these interactions is in its early stages, but may provide many answers regarding the mechanisms underlying activation of the immune system in IBS. Identifying what the key changes in the GI immune system are in IBS and how these changes modulate viscerosensory nervous function is essential for the development of novel therapies for the underlying disorder.

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Section: Discussionmentioning

confidence: 99%

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

129

117

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“…Most understanding of gut sensory innervation comes from studies in a small number of species of animals (mice, rats, guinea pigs, ferrets, cats, rabbits and sheep), although a few studies (including one dating back to the 1960s) have recorded from sensory neurons innervating human gut, in vitro. [11][12][13] To the extent that the sparse data enables conclusions, sensory nerves in human gut seem similar to those in animals.…”

Section: Sensory Innervation Of the Gutmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

237

216

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Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors, and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that there are just five structurally distinct types of sensory endings in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators.Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.2

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“…Lack of such studies has compromised targeted development of anti-nociceptive drugs to relieve visceral pain. In this issue of Gut , two papers from two independent groups represent a true breakthrough in that they demonstrate the feasibility of nerve recordings in isolated human gut preparations 11 12. Both groups have a long-standing history in performing recordings from gut afferents in various animal models 13.…”

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confidence: 99%

“…This potentially has tremendous impact as it is not known whether our concepts on sensory transmission in the gut derived from animal studies apply equally to humans. The studies by Peiris et al 11 ( see page ) and Jiang et al 12 ( see page ) describe afferent recordings from distinct preparations of resected human gut. Peiris et al 11 utilise mainly the isolated appendix in order to examine the effect of inflammatory mediators on spontaneous afferent firing while Jiang et al 12 focused on characterising the mechanosensitivity of flat-sheet preparations of colon.…”

mentioning

confidence: 99%

“…The studies by Peiris et al 11 ( see page ) and Jiang et al 12 ( see page ) describe afferent recordings from distinct preparations of resected human gut. Peiris et al 11 utilise mainly the isolated appendix in order to examine the effect of inflammatory mediators on spontaneous afferent firing while Jiang et al 12 focused on characterising the mechanosensitivity of flat-sheet preparations of colon. The two groups have to be applauded for their achievement in recording from visceral afferents in isolated viable human gut tissue as it sets the basis for further in-depth studies.…”

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confidence: 99%

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Recording from human gut tissue: a major step towards more efficient drug development?

Schemann

2011

Gut

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'First-in-man': characterising the mechanosensitivity of human colonic afferents

Cited by 28 publications

References 5 publications

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Extrinsic primary afferent signalling in the gut

Recording from human gut tissue: a major step towards more efficient drug development?

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