The effect of pain conditioning on experimentally evoked cough: evidence of impaired endogenous inhibitory control mechanisms in refractory chronic cough
Bibliographic record
Abstract
The pathophysiology of refractory chronic cough (RCC) is unclear. We hypothesised that endogenous inhibitory control mechanisms, such as those activated by noxious stimuli inducing pain (conditioned pain modulation) may be capable of inhibiting coughing and urge to cough evoked by inhaled capsaicin. Furthermore, these mechanisms may be impaired in patients with RCC. The objective was to investigate the effects of pain on cough and urge to cough in healthy volunteers and RCC patients. Healthy volunteers and RCC patients underwent a randomised, controlled, four-way crossover study comparing the effect of four interventions on capsaicin-evoked coughing and urge to cough. The interventions comprised immersing a hand in 1) noxious cold water; 2) warm water; 3) warm water, but subjects were instructed to voluntarily supress coughing; and 4) no intervention. The co-primary outcomes were numbers of evoked coughs and urge to cough scores. 20 healthy volunteers (mean± sd age 50.1±14.2 years, male:female 10:10) and 20 RCC patients (age 60.1±7.9 years, male:female 9:11) participated. Overall, noxious cold water reduced capsaicin-evoked urge-to-cough scores and cough numbers compared with warm water (1.6 (95% CI 1.3–2.0) versus 2.2 (1.8–2.6), p<0.001 and 4.8 (3.7–6.2) coughs versus 7.9 (6.7–9.5) coughs, p<0.001, respectively). Healthy volunteers and RCC patients demonstrated similar reductions in the urge to cough during noxious cold-water immersion, but noxious cold water and voluntary suppression interventions were less effective at reducing capsaicin-evoked cough in RCC patients than in healthy volunteers (p=0.041). Endogenous inhibitory control mechanisms, specifically those activated by pain, can reduce both coughing and the urge to cough. Impairment of endogenous inhibitory control mechanisms may contribute to excessive coughing in RCC.
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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 | 0.009 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.002 |
| 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".