Electrophysiological characterization of human rectal afferents

Ng, Kheng‐Seong; Brookes, Simon Jonathan; Montes-Adrian, Noemi A; Mahns, David A.; Gladman, Marc A.

doi:10.1152/ajpgi.00153.2016

Cited by 13 publications

(8 citation statements)

References 48 publications

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“…The similarities between the animal model of post-inflammatory visceral pain induced by DNBS and the clinical manifestations displayed by patients affected by both IBS and IBDs [5,13,41,42] prompted us to look deeper into the pathophysiological mechanisms involved in pain development and maintenance. DNBS animals developed a long-lasting visceral hypersensitivity to both colo-rectal and rectal stimuli, as observed in patients affected by IBS [43,44]. After the resolution of colitis elicited by DNBS, the animals developed visceral hypersensitivity, which persisted approximately for 90 days, in accordance to previous reports [12].…”

Section: Discussionsupporting

confidence: 89%

Deepening the Mechanisms of Visceral Pain Persistence: An Evaluation of the Gut-Spinal Cord Relationship

Lucarini

Parisio

Branca

et al. 2020

Cells

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The management of visceral pain is a major clinical problem in patients affected by gastrointestinal disorders. The poor knowledge about pain chronicization mechanisms prompted us to study the functional and morphological alterations of the gut and nervous system in the animal model of persistent visceral pain caused by 2,4-dinitrobenzenesulfonic acid (DNBS). This agent, injected intrarectally, induced a colonic inflammation peaking on day 3 and remitting progressively from day 7. In concomitance with bowel inflammation, the animals developed visceral hypersensitivity, which persisted after colitis remission for up to three months. On day 14, the administration of pain-relieving drugs (injected intraperitoneally and intrathecally) revealed a mixed nociceptive, inflammatory and neuropathic pain originating from both the peripheral and central nervous system. At this time point, the colonic histological analysis highlighted a partial restitution of the tunica mucosa, transmural collagen deposition, infiltration of mast cells and eosinophils, and upregulation of substance P (SP)-positive nerve fibers, which were surrounded by eosinophils and MHC-II-positive macrophages. A significant activation of microglia and astrocytes was observed in the dorsal and ventral horns of spinal cord. These results suggest that the persistence of visceral pain induced by colitis results from maladaptive plasticity of the enteric, peripheral and central nervous systems.

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Section: Discussionsupporting

confidence: 89%

Deepening the Mechanisms of Visceral Pain Persistence: An Evaluation of the Gut-Spinal Cord Relationship

Lucarini

Parisio

Branca

et al. 2020

Cells

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“…Studies of human ileum, appendix, colon (ascending, transverse, sigmoid, descending), and rectum have demonstrated the presence of afferents with function characteristics compatible with serosal (Jiang et al, 2011; Hockley et al, 2016; Yu et al, 2016; McGuire et al, 2017), mesenteric (Hockley et al, 2016; Yu et al, 2016; McGuire et al, 2017), muscular (Jiang et al, 2011; Yu et al, 2016; McGuire et al, 2017), muscular-mucosal (Jiang et al, 2011; McGuire et al, 2017), and mucosal afferents (Table 2; Yu et al, 2016). Studies by Peiris et al (2011) and Ng et al (2016) identified afferent firing in colon and rectum sensitive to focal probing but did not systematically test the effect of gut distension, or mucosal stroking, and therefore the mechanosensitive afferents identified in these studies could represent any of the mechanically-sensitive functional classes. Recruitment of “silent afferents” by inflammatory mediators has also been demonstrated in human colon (Peiris et al, 2011; Hockley et al, 2016; Yu et al, 2016; McGuire et al, 2017), including those which subsequently acquire mechanosensitivity (Ng et al, 2016).…”

Section: Distinct Classes Of Sensory Afferents Innervate the Gastroinmentioning

confidence: 96%

“…Studies by Peiris et al (2011) and Ng et al (2016) identified afferent firing in colon and rectum sensitive to focal probing but did not systematically test the effect of gut distension, or mucosal stroking, and therefore the mechanosensitive afferents identified in these studies could represent any of the mechanically-sensitive functional classes. Recruitment of “silent afferents” by inflammatory mediators has also been demonstrated in human colon (Peiris et al, 2011; Hockley et al, 2016; Yu et al, 2016; McGuire et al, 2017), including those which subsequently acquire mechanosensitivity (Ng et al, 2016). Serosal and muscular colorectal afferents are by far the most commonly reported afferent in human studies to date, with very few mucosal and muscular-mucosal afferents identified (Table 2).…”

Section: Distinct Classes Of Sensory Afferents Innervate the Gastroinmentioning

confidence: 96%

Spinal Afferent Innervation of the Colon and Rectum

Brierley

Hibberd

Spencer

2018

Front. Cell. Neurosci.

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Despite their seemingly elementary roles, the colon and rectum undertake a variety of key processes to ensure our overall wellbeing. Such processes are coordinated by the transmission of sensory signals from the periphery to the central nervous system, allowing communication from the gut to the brain via the “gut-brain axis”. These signals are transmitted from the peripheral terminals of extrinsic sensory nerve fibers, located within the wall of the colon or rectum, and via their axons within the spinal splanchnic and pelvic nerves to the spinal cord. Recent studies utilizing electrophysiological, anatomical and gene expression techniques indicate a surprisingly diverse set of distinct afferent subclasses, which innervate all layers of the colon and rectum. Combined these afferent sub-types allow the detection of luminal contents, low- and high-intensity stretch or contraction, in addition to the detection of inflammatory, immune, and microbial mediators. To add further complexity, the proportions of these afferents vary within splanchnic and pelvic pathways, whilst the density of the splanchnic and pelvic innervation also varies along the colon and rectum. In this review we traverse this complicated landscape to elucidate afferent function, structure, and nomenclature to provide insights into how the extrinsic sensory afferent innervation of the colon and rectum gives rise to physiological defecatory reflexes and sensations of discomfort, bloating, urgency, and pain.

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“…The latter function underpins the ability to selectively detect and pass flatus and may be mediated by multimodal endings such as those responding to temperature and chemicals (taste) as well as pressure. Pressure and stretch receptors are located in the myenteric plexus as intraganglionic laminar endings (IGLEs) and signal via pelvic parasympathetic nerves [ 2 , 3 ]. It is not known whether the muscularis propria also has intramuscular arrays (IMAs).…”

Section: Introductionmentioning

confidence: 99%

“…Pressure and stretch receptors are located in the myenteric plexus as intraganglionic laminar endings (IGLEs) and signal via pelvic parasympathetic nerves [ 2 , 3 ]. It is not known whether the muscularis propria also has intramuscular arrays (IMAs).…”

Section: Introductionmentioning

confidence: 99%