Identification of Medium/High-Threshold Extrinsic Mechanosensitive Afferent Nerves to the Gastrointestinal Tract

Song, Xing-Yun; Chen, Bao Nan; Zagorodnyuk, Vladimir; Lynn, Penny A.; Blackshaw, L. Ashley; Grundy, David; Brunsden, Alan M.; Costa, Marcello; Brookes, Simon Jonathan

doi:10.1053/j.gastro.2009.02.061

Cited by 87 publications

(112 citation statements)

References 47 publications

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“…They give rise to fine branching peri-arterial axons that are preferentially associated with arterial branch points. Importantly, they are not restricted to mesenteric vessels, but continue into the gut wall, innervating the arteries and second order arterioles in the submucosa, 92 but not finer branches or capillaries. The same afferent unit can have transduction sites on both mesenteric and submucosal vessels 92 .…”

Section: Type V: Spinal Vascular Afferentsmentioning

confidence: 99%

“…Importantly, they are not restricted to mesenteric vessels, but continue into the gut wall, innervating the arteries and second order arterioles in the submucosa, 92 but not finer branches or capillaries. The same afferent unit can have transduction sites on both mesenteric and submucosal vessels 92 . These afferents detect mechanical stimuli from mechanotransduction sites on both extramural and intramural blood vessels.…”

Section: Type V: Spinal Vascular Afferentsmentioning

confidence: 99%

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Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

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240

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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Section: Type V: Spinal Vascular Afferentsmentioning

confidence: 99%

Section: Type V: Spinal Vascular Afferentsmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

Self Cite

240

216

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“…Afferent endings are exposed to monocyte derived factors as they frequently line blood vessel walls which monocytes move through as they migrate from the blood stream into the colon (Song et al, 2009). The intestinal immune system is in a constant state of activation, and monocytes frequently migrate to the intestine in health (MacDonald et al, 2011).…”

mentioning

confidence: 99%

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients, Brain, Behavior, and Immunity (2014), doi: http://dx.doi.org/10. 1016/j.bbi.2014.07.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-endorphin was identified predominantly in monocyte / macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in µ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte / macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.

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“…The parietal peritoneum is innervated by the neurons of the dorsal root ganglia (DRG) that supply the muscles and the skin of the abdominal wall, whereas the visceral peritoneum is innervated by not only the neurons of the vagal ganglia but also the DRG (Warwick and Williams, 1973;Tanaka et al, 2002). There are several reports about the innervation of sensory afferent fibers in the serous membrane covering the gut (Iggo, 1986;Ward et al, 2003;Song et al, 2009;Zagorodnyuk et al, 2010). Iggo (1986) reported that there are distension-sensitive C-mechanoreceptor units in the serous membrane covering the gut or in the omentum.…”

mentioning

confidence: 99%

“…Iggo (1986) reported that there are distension-sensitive C-mechanoreceptor units in the serous membrane covering the gut or in the omentum. Song et al (2009) described that mesenteric afferent mechanosensitive nerve endings correspond to varicose branching axons on mesenteric blood vessels. However, there have been few studies about the distribution and the ultrastructure of the sensory nerves supplying the parietal peritoneum.…”

mentioning

confidence: 99%

Distribution and Ultrastructure of Afferent Fibers in the Parietal Peritoneum of the Rat

Tanaka¹,

Hayakawa²,

Maeda³

et al. 2011

The Anatomical Record

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The distribution and the ultrastructure of afferent fibers innervating the parietal peritoneum in the rat was studied with immunohistochemistry using an antiserum against the neuronal marker protein gene product 9.5. The immunoreactive fibers were distributed throughout the peritoneum. They generally ran straight and parallel to the intercostal nerves running in the abdominal muscles underlying the peritoneum. They sometimes branched and terminated by forming club-like endings. The number of nerve endings on the peritoneal surface was 3.25 AE 1.66 mm À2 . Electron microscopic observations revealed both unmyelinated and myelinated nerve fibers. The unmyelinated fibers were thin and about 1 lm in diameter. Their endings formed slight swellings located just inside the peritoneal cell layer. The myelinated fibers often formed a bundle that was composed of two or three nerve fibers. Each myelinated fiber kept in contact with a Shwann cell and projected toward the peritoneal cavity. Finally, they penetrated the peritoneal cell layer to reach the peritoneal cavity. These fibers then made contacts with the peritoneal cells and became free from the myelin sheath. The ending had a club-like shape covered with collagen fibers, and contained many neurofilaments, a few mitochondria, but no synaptic vesicles. These results suggest that since the sensory endings are exposed at the peritoneal cavity, the sensory fibers are highly sensitive to somatic or nociceptive stimuli. Anat Rec, 294:1736Rec, 294: -1742Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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Identification of Medium/High-Threshold Extrinsic Mechanosensitive Afferent Nerves to the Gastrointestinal Tract

Abstract: Background & Aims-Large distensions reliably evoke sensation from the non-inflamed, nonischemic bowel, but the specialized afferent axonal structures responsible have not been

Cited by 87 publications

References 47 publications

Extrinsic primary afferent signalling in the gut

Extrinsic primary afferent signalling in the gut

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Distribution and Ultrastructure of Afferent Fibers in the Parietal Peritoneum of the Rat

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