A52 ANTIBIOTICS WORSEN VISCERAL BUT NOT SOMATIC HYPERALGESIA IN A MOUSE MODEL OF POST-INFLAMMATORY EXPERIMENTAL COLITIS.
Bibliographic record
Abstract
Over 20% of inflammatory bowel disease (IBD) patients in endoscopic remission experience chronic abdominal pain. Studies also show widespread somatic pain in the absence of inflammation, suggesting altered central pain neurotransmission. The microbiome is known to regulate key aspects of the brain-gut axis. Microbial manipulation alters the expression of key targets in sensory neurotransmission, suggesting that the gut microbiome plays an active role in the pathogenesis of chronic pain. Our objective was to determine whether microbial manipulation alters the development of chronic visceral and somatic pain in the post-inflammatory mouse model of colitis. C57BL/6 mice were treated with the dextran sulfate sodium (DSS) (2.5 % in drinking water) for 5 days and allowed to recover for 5 weeks. The microbiome was manipulated through the administration of an antibiotic (ABX) cocktail in drinking water during the last 2 weeks of the recovery period. Visceral pain was assessed using the visceromotor reflex to colorectal distention and somatic pain was evaluated using the automated von Frey and the hot plate tests. The expression of genes known to modulate pain neurotransmission was evaluated in the brain and spinal cord. Short chain fatty acid (SCFA) levels were measured in the feces using mass spectrometry. The effects of nociceptive mediators present in the colon were evaluated by incubation of naïve DRG neurons with colonic supernatants obtained from ABX-treated and post-inflammatory DSS mice. Nociceptive sensitization was determined by evaluating capsaicin-induced TRPV1 responses in DRGs using calcium imaging. Post-inflammatory DSS-treated mice showed visceral (p<0.01), mechanical (p<0.01) and thermal (p<0.05) hyperalgesia. ABX treatment induced visceral allodynia independent of DSS treatment (p<0.05) but had no effect on the development of post-inflammatory mechanical and thermal hyperalgesia. Fecal acetate (Fold increase CT vs DSS: 2.03±0.52, p<0.05) and butyrate concentrations (Fold increase CT vs DSS: 2.27±0.44, p<0.05) were increased in post-inflammatory DSS mice. ABX but not inflammation, induced a significant increase in TRPV1 and NK1 mRNA in the spinal cord, and BDNF mRNA in the amygdala. TRPV1 responses to 100nM capsaicin stimulation were significantly increased in naïve colonic DRGs incubated with colonic supernatants from both post-inflammatory DSS (1.55±0.18, p<0.05) and ABX mice (1.86±0.29, p<0.01) compared to controls. Our work demonstrated that post-inflammatory colitis is associated with visceral and somatic hyperalgesia, similar to that seen in IBD patients in remission. Our results suggest that microbial-derived soluble factors may promote sensitization of spinal and supra spinal pain pathways. CCC
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".