Sensory innervation of the guinea pig colon and rectum compared using retrograde tracing and immunohistochemistry

Chen, B N; Olsson, Caroline; Sharrad, DF; Brookes, Simon Jonathan

doi:10.1111/nmo.12825

Cited by 7 publications

(8 citation statements)

References 53 publications

(117 reference statements)

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“…On the other hand, the relatively low number of FB+ neurons observed in this study suggest that sensory components of the vagal nerve may play more important functions in the innervation of the ICV. This is according to the previous studies, where it was found that the network of processes derived from DRG neurons in the colon is more extensive than in the stomach and jejunum [ 30 , 32 ]. This is connected with the fact that branches of the vagal nerve supply the GI tract from the oesophagus to the proximal colon [ 34 ].…”

Section: Discussionsupporting

confidence: 85%

“…The results obtained in this study indicate that the ICV, similar to other parts of the gastrointestinal tract, is supplied by neurons located in DRG [ 30 ]. Similar to previous studies, where DRG neuronal cells supplying the stomach, duodenum, ileum, and colon were described in various mammal species [ 30 , 31 , 32 , 33 ], observations made during the present investigations show that DRG plays a role in ICV sensory innervation in the domestic pig. On the other hand, the relatively low number of FB+ neurons observed in this study suggest that sensory components of the vagal nerve may play more important functions in the innervation of the ICV.…”

Section: Discussionmentioning

confidence: 97%

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Distribution and Neurochemistry of the Porcine Ileocaecal Valve Projecting Sensory Neurons in the Dorsal Root Ganglia and the Influence of Lipopolysaccharide from Different Serotypes of Salmonella spp. on the Chemical Coding of DRG Neurons in the Cell Cultures

Mikołajczyk

Kozłowska

Gonkowski

2018

IJMS

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The ileocecal valve (ICV)—a sphincter muscle between small and large intestine—plays important roles in the physiology of the gastrointestinal (GI) tract, but many aspects connected with the innervation of the ICV remain unknown. Thus, the aim of this study was to investigate the localization and neurochemical characterization of neurons located in the dorsal root ganglia and supplying the ICV of the domestic pig. The results have shown that such neurons mainly located in the dorsal root ganglia (DRG) of thoracic and lumbar neuromers show the presence of substance P (SP), calcitonin gene-related peptide (CGRP), and galanin (GAL). The second part of the experiment consisted of a study on the influence of a low dose of lipopolysaccharide (LPS) from Salmonella serotypes Enteritidis Minnesota and Typhimurium on DRG neurons. It has been shown that the LPS of these serotypes in studied doses does not change the number of DRG neurons in the cell cultures, but influences the immunoreactivity to SP and GAL. The observed changes in neurochemical characterization depend on the bacterial serotype. The results show that DRG neurons take part in the innervation of the ICV and may change their neurochemical characterization under the impact of LPS, which is probably connected with direct actions of this substance on the nervous tissue and/or its pro-inflammatory activity.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 97%

Distribution and Neurochemistry of the Porcine Ileocaecal Valve Projecting Sensory Neurons in the Dorsal Root Ganglia and the Influence of Lipopolysaccharide from Different Serotypes of Salmonella spp. on the Chemical Coding of DRG Neurons in the Cell Cultures

Mikołajczyk

Kozłowska

Gonkowski

2018

IJMS

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“…The CGRP-expressing extrinsic afferent neurons in the rodent gut (Figure 1) originate primarily from cell bodies in the dorsal root ganglia (Sternini et al, 1987;Green and Dockray, 1988;Mulderry et al, 1988;Sternini and Anderson, 1992;Robinson et al, 2004;Tan et al, 2008;Chen et al, 2016). Within the gastrointestinal tract, they supply primarily the arterial system but also project to the submucosal and myenteric nerve plexus, to the circular and longitudinal muscle layers and the lamina propria of the mucosa (Sternini et al, 1987;Su et al, 1987;Green and Dockray, 1988).…”

Section: Innervation Of the Gut By Calcitonin Gene-related Peptide-expressing Neuronsmentioning

confidence: 99%

Constipation Caused by Anti-calcitonin Gene-Related Peptide Migraine Therapeutics Explained by Antagonism of Calcitonin Gene-Related Peptide’s Motor-Stimulating and Prosecretory Function in the Intestine

Holzer

Holzer‐Petsche

2022

Front. Physiol.

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The development of small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) and of monoclonal antibodies targeting the CGRP system has been a major advance in the management of migraine. In the randomized controlled trials before regulatory approval, the safety of these anti-CGRP migraine therapeutics was considered favorable and to stay within the expected profile. Post-approval real-world surveys reveal, however, constipation to be a major adverse event which may affect more than 50% of patients treated with erenumab (an antibody targeting the CGRP receptor), fremanezumab or galcanezumab (antibodies targeting CGRP). In this review article we address the question whether constipation caused by inhibition of CGRP signaling can be mechanistically deduced from the known pharmacological actions and pathophysiological implications of CGRP in the digestive tract. CGRP in the gut is expressed by two distinct neuronal populations: extrinsic primary afferent nerve fibers and distinct neurons of the intrinsic enteric nervous system. In particular, CGRP is a major messenger of enteric sensory neurons which in response to mucosal stimulation activate both ascending excitatory and descending inhibitory neuronal pathways that enable propulsive (peristaltic) motor activity to take place. In addition, CGRP is able to stimulate ion and water secretion into the intestinal lumen. The motor-stimulating and prosecretory actions of CGRP combine in accelerating intestinal transit, an activity profile that has been confirmed by the ability of CGRP to induce diarrhea in mice, dogs and humans. We therefore conclude that the constipation elicited by antibodies targeting CGRP or its receptor results from interference with the physiological function of CGRP in the small and large intestine in which it contributes to the maintenance of peristaltic motor activity, ion and water secretion and intestinal transit.

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“…27 The neuronal influence on the inflammatory state of the gastrointestinal tract in IBD is well known, 28,29 and gut immune cells express receptors for a range of neurotransmitters, including CGRP, substance P, vasoactive intestinal peptide, or nitric oxide synthase. 30,31 CGRP and its two isoforms (alpha and beta) have distinctive actions. While beta-CGRP is primarily released by primary afferent Dogiel type 2 neurons in the enteric nervous system, alpha-CGRP is liberated by neurons from the vagus nerve and the dorsal root ganglia in the spinal cord via splanchnic and pelvic nerves.…”

Section: Backg Rou N Dmentioning

confidence: 99%

Differences in circulating alpha‐calcitonin gene–related peptide levels in inflammatory bowel disease and its relation to migraine comorbidity: A cross‐sectional study

Pascual‐Mato,

Gárate,

González‐Quintanilla

et al. 2024

Headache

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ObjectiveTo analyze the specificity of calcitonin gene–related peptide (CGRP) levels, we measured alpha‐CGRP circulating levels in a large series of patients with a recent diagnosis of inflammatory bowel disease (IBD) who were interviewed regarding comorbid headache.BackgroundSeveral studies have found an association between migraine and IBD.MethodsIn this cross‐sectional study performed in an IBD clinic, morning serum alpha‐CGRP levels were measured by enzyme‐linked immunosorbent assay in 96 patients who were recently diagnosed with IBD and compared to those from 50 similar patients with chronic migraine (CM) and 50 healthy controls (HC).ResultsAlpha‐CGRP levels were higher in patients with IBD (median [interquartile range] 56.9 [35.6–73.9] pg/mL) and patients with CM (53.0 [36.7–73.9] pg/mL) compared to HC (37.2 [30.0–51.8] pg/mL; p = 0.003; p = 0.019, respectively). Regarding IBD diagnostic subtypes, alpha‐CGRP levels for ulcerative colitis (67.2 ± 49.3 pg/mL; 57.0 [35.6–73.4] pg/mL) and Crohn's disease (54.9 ± 27.5 pg/mL; 57.7 [29.1–76.1] pg/mL) were significantly higher than those of HC (p = 0.013, p = 0.040, respectively). Alpha‐CGRP levels were further different in patients with IBD with migraine (70.9 [51.8–88.7] pg/mL) compared to HC (p < 0.001), patients with IBD without headache (57.5 [33.3–73.8] pg/mL; p = 0.049), and patients with IBD with tension‐type headache but without migraine (41.7 [28.5–66.9] pg/mL; p = 0.004), though alpha‐CGRP levels in patients with IBD without migraine (53.7 [32.9–73.5] pg/mL) remained different over HC (p = 0.028).ConclusionTogether with CM, circulating alpha‐CGRP levels are different in patients with IBD, perhaps reflecting a chronic inflammatory state. IBD is an example of how alpha‐CGRP levels are not a totally specific migraine biomarker. However, alpha‐CGRP levels were further increased in patients with IBD who have a history of migraine, which reinforces its role as a biomarker in migraine patients, always bearing in mind their comorbidities.

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Sensory innervation of the guinea pig colon and rectum compared using retrograde tracing and immunohistochemistry

Abstract: Running Title:Extrinsic sensory nerves to rectum and colon Abbreviations:DiI; DiIC12(3) (1,1'-Didodecyl-3,3,3',3'-Tetramethylindocarbocyanine Perchlorate) or a 1:1 mixture of DiIC12 (3)

Cited by 7 publications

References 53 publications

Distribution and Neurochemistry of the Porcine Ileocaecal Valve Projecting Sensory Neurons in the Dorsal Root Ganglia and the Influence of Lipopolysaccharide from Different Serotypes of Salmonella spp. on the Chemical Coding of DRG Neurons in the Cell Cultures

Distribution and Neurochemistry of the Porcine Ileocaecal Valve Projecting Sensory Neurons in the Dorsal Root Ganglia and the Influence of Lipopolysaccharide from Different Serotypes of Salmonella spp. on the Chemical Coding of DRG Neurons in the Cell Cultures

Constipation Caused by Anti-calcitonin Gene-Related Peptide Migraine Therapeutics Explained by Antagonism of Calcitonin Gene-Related Peptide’s Motor-Stimulating and Prosecretory Function in the Intestine

Differences in circulating alpha‐calcitonin gene–related peptide levels in inflammatory bowel disease and its relation to migraine comorbidity: A cross‐sectional study

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