Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.

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Sini-San Regulates the NO-cGMP-PKG Pathway in the Spinal Dorsal Horn in a Modified Rat Model of Functional Dyspepsia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/3575231 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Zhenyu Wu ◽

Xiaofang Lu ◽

Shengsheng Zhang ◽

Chunyang Zhu

Keyword(s):

Gene Expression ◽

Dorsal Horn ◽

Functional Dyspepsia ◽

Rat Model ◽

Spinal Dorsal Horn ◽

Visceral Hypersensitivity ◽

Enzyme Linked Immunosorbent Assay ◽

Gastric Distention ◽

Real Time Quantitative Pcr ◽

Spinal Dorsal

The present study investigated the effect of Chinese medicine Sini-San (SNS) on visceral hypersensitivity in a rat model of functional dyspepsia (FD), and it explored related underlying mechanisms. The rat model of FD was developed by combining neonatal iodoacetamide (IA) treatment and adult tail-clamping. After SNS treatment, the behavior and electromyographic testing were performed to evaluate the visceromotor responses of rats to gastric distention. Immunofluorescence was used to detect the distribution of iNOS-positive cells in the spinal dorsal horn, while the real-time quantitative PCR and western blot were used for detection of the gene expression of c-fos, iNOS, and GABAb and protein levels of iNOS and GABAb in the spinal dorsal horn, respectively. The protein concentration of cGMP and PKG proteins in the spinal dorsal horn were quantified by enzyme-linked immunosorbent assay. In this study, SNS treatment significantly reduced the behavioral score and electromyographic response to graded intragastric distension pressure. The middle-dose of SNS treatment significantly reduced the distribution of iNOS-positive cells in the spinal dorsal horn of FD model rats. The gene expression of c-fos, iNOS, and GABAb and the protein contents of iNOS, GABAb, cGMP, and PKG in the spinal dorsal horn of FD model rats were restored to a normal level by middle-dose of SNS treatment. Our results suggest that Sini-San may alleviate the visceral hypersensitivity in FD model rats via regulation of the NO/cGMP/PKG pathway in the spinal dorsal horn.

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Tu1647 - The Role of Dectin-1 and Mast Cells in Visceral Hypersensitivity in Patients with Diarrhea-Predominant Irritable Bowel Syndrome

Gastroenterology ◽

10.1016/s0016-5085(18)33291-8 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-980-S-981

Author(s):

Chao Li ◽

Yan Chi

Keyword(s):

Irritable Bowel Syndrome ◽

Mast Cells ◽

Visceral Hypersensitivity ◽

Irritable Bowel

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Role of Nociceptors/Neuropeptides in the Pathogenesis of Visceral Hypersensitivity of Nonerosive Reflux Disease

Digestive Diseases and Sciences ◽

10.1007/s10620-012-2337-7 ◽

2012 ◽

Vol 58 (8) ◽

pp. 2237-2243 ◽

Cited By ~ 25

Author(s):

Norimasa Yoshida ◽

Masaaki Kuroda ◽

Takahiro Suzuki ◽

Kazuhiro Kamada ◽

Kazuhiko Uchiyama ◽

...

Keyword(s):

Reflux Disease ◽

Visceral Hypersensitivity ◽

Nonerosive Reflux Disease

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Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia

International Journal of Molecular Sciences ◽

10.3390/ijms222413609 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13609

Author(s):

Lucas Wauters ◽

Raúl Y. Tito ◽

Matthias Ceulemans ◽

Maarten Lambaerts ◽

Alison Accarie ◽

...

Keyword(s):

Functional Dyspepsia ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Potential Role ◽

Short Term ◽

Beneficial Effects ◽

Rrna Sequencing ◽

Before And After

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.

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