A52 ANTIBIOTICS WORSEN VISCERAL BUT NOT SOMATIC HYPERALGESIA IN A MOUSE MODEL OF POST-INFLAMMATORY EXPERIMENTAL COLITIS.
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Notice bibliographique
Résumé
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
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle