A18 DIETARY ANTIGEN RE-CHALLENGE INCREASES NOCICEPTIVE NEURON EXCITABILITY IN A POST-INFECTIOUS IBS MODEL.
Bibliographic record
Abstract
Infectious gastroenteritis is a risk factor for development of Irritable Bowel Syndrome (IBS). Exposure to the dietary antigen ovalbumin (OVA) during infection with Citrobacter rodentium resulted in an increased visceromotor response to colonic distension and increased mucosal permeability following re-challenge with OVA. It is unknown whether colonic immune mediators released following re-challenge of OVA could subsequently increase the excitability of nociceptive neurons. Determine whether colonic mediators released in response to dietary antigen re-challenge increase excitability of nociceptive neurons and whether the histamine receptor H1 is involved in a model of post infectious IBS. Mice were infected with C. rodentium in the presence (infected OVA/OVA) or absence of OVA (infected saline/OVA) and were subsequently re-challenged with OVA 5 weeks post-infection. A third group of mice were not infected but exposed to OVA and re-challenged with OVA at 5 weeks (non-infected OVA/OVA). Following OVA re-challenge, mice were euthanized and the colons were incubated in media, supernatants were collected after 4 hrs. Supernatants were incubated overnight with nociceptive DRG neurons from control mice. Perforated patch clamp recordings were employed to assess neuronal excitability by measuring rheobase (minimum current to evoke an action potential) and action potential discharge (AP) at twice rheobase. Some DRG neurons were also pre-incubated with the H1 receptor antagonist pyrilamine (1µM) 1 hour prior to incubation with supernatants. Two-way ANOVA with Bonferroni post hoc test were used to analyze the data. Infected OVA/OVA supernatants decreased the rheobase compared to the other two groups (Infected OVA/OVA= 68 ± 4.2 pA* vs Non-infected OVA/OVA= 81.2 ± 4 pA vs Infected saline/OVA = 85.6 ± 4.5 pA; *p<0.05, n= 17–19). Similarly, infected OVA/OVA supernatant also increased action potential discharge at twice rheobase (1.7 ± 0.2* vs 1.2 ± 0.1 vs 1.2 ± 0.1; *p<0.05, n= 17–19). Pyrilamine reversed the effect of infected OVA/OVA supernatant on DRG neurons (rheobase= 88.8 ± 5.5 pA, p < 0.01; AP= 1.3 ± 0.1, p= NS, n= 16) but had no effect on supernatants from the other two groups. Colonic supernatants following re-challenge with OVA increased excitability of DRG nociceptive neurons only in mice first exposed to OVA at the time of a gastrointestinal infection and this effect was inhibited by an H1 antagonist. This suggests that exposure to a dietary antigen at the time of gastrointestinal infection may prime the immune system such that re-exposure to the antigen induces release of immune mediators (e.g. histamine) resulting in increased pain signalling. CIHR
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".