Emerging studies of human visceral nociceptors

Reed, David E.; Vanner, Stephen

doi:10.1152/ajpgi.00391.2016

Cited by 3 publications

(2 citation statements)

References 47 publications

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“…Antibiotics are the most frequently prescribed drugs in children [1]. Gastrointestinal symptoms are often associated with antibiotic treatment because of related alterations in motility, permeability, nociceptors, and microbiota [2][3][4]. Antibiotic-associated diarrhea (AAD), the most commonly reported gastrointestinal manifestation, is defined as the presence of at least 3 loose or liquid bowel movements per day during or after antibiotic treatment excluding other etiologies (infections, food poisoning, use of laxatives, and chronic gastrointestinal diseases) [5,6].…”

Section: Introductionmentioning

confidence: 99%

Risk and Protective Factors for Gastrointestinal Symptoms associated with Antibiotic Treatment in Children: A Population Study

Baù

Moretti

Bertoni

et al. 2020

Pediatr Gastroenterol Hepatol Nutr

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Purpose: Gastrointestinal symptoms are often related to antibiotic treatment. Their incidence, risk and protective conditions in children are not well defined and represent the aims of this study. Methods: We prospectively enrolled inpatient children submitted to antibiotic treatment. Indication, type, dose and duration of treatment, probiotic supplementation and gastrointestinal symptoms were recorded at recruitment, after two and four weeks. Antibiotic-associated diarrhea (AAD) was defined as the presence of at least 3 loose/liquid stools within 14 days from antibiotic onset. Results: AAD occurred in 59/289 (20.4%) of patients, with increased risk in children younger than 3 years (relative risk [RR]=4.25), in lower respiratory (RR=2.11) and urinary infections (RR=3.67), intravenous administration (RR=1.81) and previous AAD episodes (RR=1.87). Abdominal pain occurred in 27/289 (9.3%), particularly in children >6 years (RR=4.15), with previous abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain (RR=0.37 and 0.24). Conclusion: AAD occurred in 20.4% of children, with increased risk at younger age, lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri reduced both AAD and associated abdominal pain.

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Section: Introductionmentioning

confidence: 99%

Risk and Protective Factors for Gastrointestinal Symptoms associated with Antibiotic Treatment in Children: A Population Study

Baù

Moretti

Bertoni

et al. 2020

Pediatr Gastroenterol Hepatol Nutr

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“…Of the internal organs, the more highly innervated are the hollow organs, such as the intestines, bladder and uterus, which are more likely to be exposed to external hazardous agents. The solid organs, such as the liver and spleen, have fewer nociceptors, and therefore, the deterioration of these organs can go unnoticed by patients (reviewed in Cervero, 2009;Reed & Vanner, 2017).…”

Section: Nociceptorsmentioning

confidence: 99%

Investigating the antinociceptive effects of N-docosahexaenoyl ethanolamine and novel kappa opioid receptor agonists

Paton¹

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<p>Chronic pain causes patients to endure prolonged suffering and discomfort, often having profound effects on quality of life. In New Zealand, one in five people currently suffer from chronic pain. To treat chronic pain, patients are typically prescribed drugs that activate the mu opioid receptor (MOPr), such as morphine, codeine and oxycodone. In recent years in the United States of America, there has been a rapid increase in the use of prescription and non-prescription opioid drugs, with opioid overdoses now the leading cause of accidental death. In New Zealand, daily doses of prescription opioids quadrupled in the ten year period from 2001-2011. Clearly, there is a need for the development of more effective and safe medications. This thesis evaluated two classes of non-addictive compounds: bioactive lipids and kappa opioid receptor (KOPr) agonists. N-docosahexaenoyl ethanolamine (DHEA) is an N-acyl ethanolamine class lipid that is structurally similar to the endocannabinoid anandamide. DHEA has previously been shown to have immune-modulatory effects in vitro, however, the in vivo effects have not previously been tested. Using the intraplantar 2% formaldehyde model in mice, DHEA reduced inflammatory and nociceptive pain via both intraperitoneal (i.p.) and local intraplantar (i.pl.) administration. DHEA significantly reduced formaldehyde-induced footpad oedema and reduced the infiltration of neutrophils into the inflamed tissue. The antinociceptive and anti-oedematous effects were not modulated by pre-treatment with either cannabinoid 1- or 2-type receptor antagonists. DHEA did not have any effect in a thermal nociceptive pain model and did not show any motor coordination impairment or changes in thermoregulation. In the search for non-addictive analgesics, KOPr agonists are a promising alternative. In contrast to MOPr agonists, KOPr agonists play a critical role in regulating the reward system. Salvinorin A (SalA) is a selective KOPr agonist that has antinociceptive and anti-inflammatory effects in vivo, with limited abuse potential. However, the short duration of action and aversive side effects limit the clinical usefulness. The present study aimed to investigate the antinociceptive effects of acute administration of novel analogues of SalA. In the dose-response tail withdrawal assay, SalA and the novel analogues 16-Ethynyl SalA and 16-Bromo SalA were more potent than the traditional KOPr agonist U50,488, and 16-Ethynyl SalA was more efficacious. 16-Ethynyl SalA and 16-Bromo SalA both had a longer duration of action in the warm water tail withdrawal assay and the hot plate test compared to SalA. In the intraplantar 2% formaldehyde test, SalA, 16-Ethynyl SalA and 16-Bromo SalA significantly reduced nociceptive pain and inflammatory pain, effects which were reversed by the KOPr antagonist nor-binaltorphimine. SalA, 16-Ethynyl SalA and 16-Bromo SalA reduced paw oedema and reduced the infiltration of neutrophils into the inflamed tissue. However, SalA, 16-Ethynyl SalA and 16-Bromo SalA produced motor incoordination effects. However, 16-Ethynyl SalA did not alter thermoregulation. The KOPr agonists were further assessed in a model of paclitaxel-induced neuropathic pain. In the acute dose-response experiment, 16-Ethynyl SalA was significantly more potent at reducing mechanical allodynia compared to morphine in both male and female mice. SalA and 16-Ethynyl SalA were more potent at reducing cold allodynia than morphine. In a chronic administration model over 22 days, for the treatment of cold and mechanical allodynia, all of the opioid treatments reduced pain, however, the traditional KOPr agonist U50,488, was the most potent, by reducing the male mechanical allodynia and cold allodynia in both sexes back to baseline levels. The ultrastructure of the sciatic nerves were studied, however, it was found that U50,488 did not reverse the effects of paclitaxel on myelin degeneration and mitochondrial damage. Overall, this study has identified DHEA as a modest treatment for inflammatory pain, with reduced side effects and a mechanism of action in contrast to other compounds with a similar structure. The novel KOPr agonists had significant effects in acute pain models with longer duration of action than the parent compound SalA. This is the first known study to investigate the effects of KOPr agonists in a paclitaxel-induced neuropathic pain model, showing that KOPr agonists are a potential therapeutic avenue for this debilitating condition.</p>

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Protease-Induced Excitation of Dorsal Root Ganglion Neurons in Response to Acute Perturbation of the Gut Microbiota Is Associated With Visceral and Somatic Hypersensitivity

Baker,

Sessenwein,

Wood

et al. 2024

Cellular and Molecular Gastroenterology and Hepatology

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Emerging studies of human visceral nociceptors

Cited by 3 publications

References 47 publications

Risk and Protective Factors for Gastrointestinal Symptoms associated with Antibiotic Treatment in Children: A Population Study

Risk and Protective Factors for Gastrointestinal Symptoms associated with Antibiotic Treatment in Children: A Population Study

Investigating the antinociceptive effects of N-docosahexaenoyl ethanolamine and novel kappa opioid receptor agonists

Protease-Induced Excitation of Dorsal Root Ganglion Neurons in Response to Acute Perturbation of the Gut Microbiota Is Associated With Visceral and Somatic Hypersensitivity

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