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The Effect of Pain Conditioning on Experimentally Evoked Cough: Evidence of Impaired Endogenous Inhibitory Control Mechanisms in Refractory Chronic Cough

Hilton, Emma; Satia, Imran; Holt, Kimberley; Woodcock, Ashley A.; Belcher, John; Smith, Jaclyn A.

Authors

Emma Hilton

Imran Satia

Kimberley Holt

Ashley A. Woodcock

Jaclyn A. Smith



Abstract

Background: The pathophysiology of refractory chronic cough (RCC) is unclear. We hypothesised that endogenous inhibitory control mechanisms, such as those activated by painful stimuli (conditioned pain modulation (CPM)), may be capable of inhibiting coughing and urge to cough evoked by inhaled capsaicin. Furthermore, these mechanisms may be impaired in patients with RCC.
Objective: To investigate the effects of CPM on cough and urge to cough (UTC) in healthy volunteers (HV) and RCC.
Methods: HV and RCC patients underwent a randomised, controlled, 4-way cross-over study comparing the effect of 4 interventions on capsaicin evoked coughing and UTC. The interventions comprised immersing a hand in i) painful cold-water, ii) warm water, iii) warm water but instructed to voluntarily supress coughing and iv) no intervention. The co-primary outcomes were numbers of evoked coughs and UTC scores.
Results: Twenty HV (mean age 50.1(±SD14.2), M:F 10:10) and 20 RCC (age 60.1(±7.9), M:F 9:11) participated. Overall, painful cold water reduced capsaicin evoked UTC scores and cough numbers compared with warm water (1.6 (95% C.I. 1.3-2.0) vs 2.2 (1.8-2.6) p<0.001; 4.8 coughs (3.7-6.2) vs 7.9 coughs (6.7-9.5) p<0.001, respectively). HV and RCC demonstrated similar reductions in the UTC during painful cold-water immersion, but painful cold water and voluntary suppression interventions were less effective in RCC than HV in reducing capsaicin evoked cough (p=0.041).

Journal Article Type Article
Acceptance Date Jun 28, 2020
Publication Date Jul 23, 2020
Publicly Available Date Mar 29, 2024
Journal European Respiratory Journal
Print ISSN 0903-1936
Electronic ISSN 1399-3003
Publisher European Respiratory Society
Peer Reviewed Peer Reviewed
Volume 56
Issue 6
Pages 2001387 - 2001387
DOI https://doi.org/10.1183/13993003.01387-2020
Keywords chronic cough, chronic pain, conditioned pain modulation, descending inhibitory control
Publisher URL https://erj.ersjournals.com/content/early/2020/07/02/13993003.01387-2020