Spinal Afferent Innervation of the Colon and Rectum

Brierley, Stuart M.; Hibberd, Timothy J.; Spencer, Nick J.

doi:10.3389/fncel.2018.00467

Cited by 82 publications

(69 citation statements)

References 149 publications

(331 reference statements)

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“…Thus, glial intercellular communication through Cx43 plays an important role in the transition to chronic visceral hypersensitivity following inflammation. CRD primarily tests the sensitivity of mechanosensitive spinal afferents that innervate the seromuscular layer of the mouse colon ( Brierley et al, 2018 ; Feng et al, 2012 ). Given that the mild colitis driven by our relatively low-dose DSS model was not sufficient to induce significant neurodegeneration in the myenteric plexus ( Figures 1G and 1H ), we speculated that the observed effects of glial Cx43 signaling could be mediated through neuro-immune signaling rather than direct effects of glia on neuroplasticity.…”

Section: Resultsmentioning

confidence: 99%

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

et al. 2020

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SUMMARY Mechanisms resulting in abdominal pain include altered neuro-immune interactions in the gastrointestinal tract, but the signaling processes that link immune activation with visceral hypersensitivity are unresolved. We hypothesized that enteric glia link the neural and immune systems of the gut and that communication between enteric glia and immune cells modulates the development of visceral hypersensitivity. To this end, we manipulated a major mechanism of glial intercellular communication that requires connexin-43 and assessed the effects on acute and chronic inflammation, visceral hypersensitivity, and immune responses. Deleting connexin-43 in glia protected against the development of visceral hypersensitivity following chronic colitis. Mechanistically, the protective effects of glial manipulation were mediated by disrupting the glial-mediated activation of macrophages through the macrophage colony-stimulating factor. Collectively, our data identified enteric glia as a critical link between gastrointestinal neural and immune systems that could be harnessed by therapies to ameliorate abdominal pain.

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Section: Resultsmentioning

confidence: 99%

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

et al. 2020

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“…This could be due to the thinness of esophageal tissue in mice, where low intensity mucosal stroking (10 mg von Frey hair) also evokes distension and makes differentiation of tension and tension-mucosal receptors impossible (Page et al, 2002). No anatomical studies have reported the structural existence of this vagal subtype in the gut wall, although an analogue, i.e., mucosal-muscular receptor, has been described in the pelvic and sacral spinal pathway of mouse (Brierley et al, 2018). Studies have proposed that mucosal-muscular afferent endings terminate in the mucosal and muscular layer of the gut wall (Page and Blackshaw, 1998;Brierley et al, 2004), however, it has also been suggested that responses to both tension and mucosal stimuli are transduced at the subepithelial plexus (Brookes et al, 2013).…”

Section: Tension-mucosal Receptorsmentioning

confidence: 99%

Dissecting the Role of Subtypes of Gastrointestinal Vagal Afferents

2020

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Gastrointestinal (GI) vagal afferents convey sensory signals from the GI tract to the brain. Numerous subtypes of GI vagal afferent have been identified but their individual roles in gut function and feeding regulation are unclear. In the past decade, technical approaches to selectively target vagal afferent subtypes and to assess their function has significantly progressed. This review examines the classification of GI vagal afferent subtypes and discusses the current available techniques to study vagal afferents. Investigating the distribution of GI vagal afferent subtypes and understanding how to access and modulate individual populations are essential to dissect their fundamental roles in the gut-brain axis.

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“…In rodents, the majority are located in dorsal root ganglia (DRG) in spinal levels lumbar 6 and sacral 1 (L6-S1; Dang et al, 2005;Xu and Gebhart, 2008;Forrest et al, 2013); we refer to these as "sacral" DRG as they are functionally equivalent to neurons found exclusively in sacral levels in humans. Pelvic visceral sensory neurons comprise two major classes, those with lightly myelinated (A-d ) or unmyelinated (C) axons (Dang et al, 2005;Franken et al, 2014;de Groat et al, 2015;Gebhart and Bielefeldt, 2016;Brierley et al, 2018). Many express transient receptor potential (TRP) channels that transduce noxious stimuli, including Trpv1, Trpa1, and Trpm8 (Skryma et al, 2011;Franken et al, 2014;Merrill et al, 2016), which are also expressed in subpopulations of somatic nociceptors (Patapoutian et al, 2009;Julius, 2013).…”

Section: Introductionmentioning

confidence: 99%

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Smith-Anttila

Mason

Wells

et al. 2020

eNeuro

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Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially leading to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively of somatic sensory neurons. This was performed in adult and E18.5 male and female mice. By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal levels. We identified many novel genes that had not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways.In this study of mouse dorsal root ganglia (DRG), we have identified numerous features of sensory neurons that vary between lumbar and sacral spinal levels and that are potentially involved in unique physiology and pathophysiology of visceral sensation and pain. We further identify maturational components of this sacral visceral transcriptome by comparing data from embryonic and adult mice. There are limited sex differences across the transcriptome of embryonic or adult sensory ganglia, but in adults these can be revealed in sacral levels and especially in Trpv1 nociceptive neurons. These datasets will encourage identification of new tools to modify mature or developing sensory neurons and adult nociceptive pathways.

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Spinal Afferent Innervation of the Colon and Rectum

Cited by 82 publications

References 149 publications

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

Dissecting the Role of Subtypes of Gastrointestinal Vagal Afferents

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

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