A290 BILE SIGNALING TO SPINAL AFFERENT NERVES INNERVATING THE MOUSE DISTAL COLON
Bibliographic record
Abstract
In a subpopulation of IBS patients, bile acids are increased in the colon and may trigger abdominal discomfort. However, little is known about activation of spinal afferent nerves (i.e. nociceptive nerves) innervating the colon by bile acids. The aim of this study was to examine activation of these nerves by primary and secondary bile acids. An in vitro preparation of the C57BL/6 mouse distal colon was employed to perform extracellular recordings of single serosal spinal afferent units en route to the inferior mesenteric ganglion. Human bile, mouse bile or bile acids (or their respective salt) were applied to the receptive field of a single afferent unit for 5 minutes via a small metal ring. The effect of the primary bile salt sodium cholate (300μM and 1mM) and the secondary bile acid/salt deoxycholic acid/sodium deoxcholate (100μM-1mM) was also examined. Nerve excitability was assessed by changes in spontaneous action potential frequency as well following mechanical stimulation of the single unit’s receptive field with a calibrated von Frey filament (1g) before and after application of bile acids/salts. Units were considered responders if the spontaneous firing rate increased 25% above baseline. Data are expressed as mean±SEM. Human bile evoked a response in all 4 units tested (control: 0.77 ± 0.43Hz; bile: 1.68 ± 0.23Hz). Application of diluted bile also activated single units (1:3 dilution: 3/3 units; 1:10 dilution: 3/4 units; 1:30 dilution: 2/3 units; 1:100 dilution: 2/3 units). Similarly, non-dilute mouse bile also activated 3/3 units tested (control: 0.94 ± 0.39Hz; bile: 2.16 ± 0.68Hz). Application of sodium cholate only activated 1/5 units when applied at concentrations of 300μM and 1mM. Deoxycholic acid or sodium deoxycholate activated 1/8 units with 100μM; 2/6 units with 300μM; and 2/9 with 1mM. Mechanical stimulation was unchanged following application of sodium cholate 300μM (10.5 ± 2.4Hz vs 7.1 ± 2.0; p>0.05, n=4) or 1mM (14.9 ± 2.7Hz vs 8.3 ± 1.8Hz; p>0.5, n=4). Mechanical sensitivity was also unchanged following deoxycholic acid or sodium deoxycholate (100μM-1mM) (p>0.05, n=6–9). Bile is a potent stimulus to activate nociceptive nerves in the distal colon. However, a major primary bile salt and a major secondary bile acid/salt activated few of these nerves and did not change mechanosensitivity. This suggests that either a combination of bile acids/salts or another constituent within bile activates colonic afferent nerves. None
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".