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.

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).

Citation

Hilton, E., Satia, I., Holt, K., Woodcock, A. A., Belcher, J., & Smith, J. A. (2020). The Effect of Pain Conditioning on Experimentally Evoked Cough: Evidence of Impaired Endogenous Inhibitory Control Mechanisms in Refractory Chronic Cough. European Respiratory Journal, 56(6), 2001387 - 2001387. https://doi.org/10.1183/13993003.01387-2020

• Journal Article Type: Article
• Acceptance Date: Jun 28, 2020
• Publication Date: Jul 23, 2020
• 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