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The pathophysiology of refractory chronic cough (RCC) is unclear. We hypothesised that endogenous inhibitory control mechanisms, such as those activated by noxiousstimuli inducing pain (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.The objective was to investigate the effects of pain on cough and urge to cough (UTC) in healthy volunteers (HV) and RCC. 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) noxious 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.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, noxious cold water reduced capsaicin evoked UTC scores and cough numbers compared with warm water (1.6 (95% C.I. 1.3-2.0) versus 2.2 (1.8-2.6) p&lt;0.001; 4.8 coughs (3.7-6.2) versus 7.9 coughs (6.7-9.5) p&lt;0.001, respectively). HV and RCC demonstrated similar reductions in the UTC during noxious cold-water immersion, but noxious cold water and voluntary suppression interventions were less effective in RCC than HV in reducing capsaicin evoked cough (p=0.041).Endogenous inhibitory control mechanisms, specifically those activated by pain, can reduce both coughing and the UTC. Impairment of endogenous inhibitory control mechanisms may contribute to excessive coughing in RCC.

european respiratory journal/the european respiratory journal

The effect of pain conditioning on experimentally evoked cough: evidence of impaired endogenous inhibitory control mechanisms in refractory chronic cough