S144a Endogenous inhibition of experimentally induced cough in healthy subjects

Abstract

Background The pathophysiology of chronic cough may include peripheral/central sensitisation of afferent pathways and/or a failure of inhibitory pathways. Cough can be voluntarily suppressed in healthy subjects, but the role of endogenous inhibition is unknown. Endogenous inhibitory pain pathways can be activated by applying a painful conditioning stimulus to one body part, to inhibit pain elsewhere, described as “Diffuse Noxious Inhibitory Controls”. Aim To investigate if a painful conditioning stimulus applied to the hand would inhibit cough in healthy subjects. Methods This was a randomised, 4-way, cross-over study. The EC50 dose of capsaicin was pre-determined (inducing at least 50% maximal cough frequency) at screening, and subsequently administered at each of the 4 visits (>48 h apart) in 2 blocks (1 h apart) of 4 inhalations (15 s apart), simultaneous with a randomised intervention: Coughs were counted and verified using sound recordings. Urge-to-cough was rated using a Modfied Borg Scale (0–10). Analysis The between-block change in cough frequency and urge-to-cough intensity was compared by intervention using paired t-tests after adjusting for an order-effect. Primary outcome was W versus C. Secondary outcomes were B versus W, and W versus S. Results 20 non-smoking healthy subjects [10 male; mean (SD) age 55.05 (14.2) yrs] with normal lung function and median (IQR) EC50 of 15.6 (23.50) μM capsaicin completed the study. Compared to B, W had no significant effect on cough (p=0.623) or urge-to-cough (p=0.285). Compared to W, C significantly reduced cough (p=0.048) ([Abstract S144a figure 1A][1]) and showed a trend towards a reduction in urge-to-cough (p=0.104) ([Abstract S144a figure 1B][1]). Compared to W, S significantly reduced cough (p=0.016) (see [Abstract S144a figure 1C][1]) but urge-to-cough did not change (p=0.631) ([Abstract S144a figure 1D][1]). ![Abstract S144a Figure 1][2] Abstract S144a Figure 1 Change in total cough frequency (A,C) and urge-to-cough intensity (B,D) between blocks. Horizontal lines show mean, error bars ±95% CI. Conclusion Applying a painful stimulus to the hand inhibits cough in healthy subjects, and may be a useful model for measuring endogenous inhibition of coughing. Further studies to investigate whether chronic cough patients demonstrate impaired inhibition using this experimental paradigm are underway. [1]: #F1 [2]: pending:yes