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Pathophysiology and management of cough
S144a Endogenous inhibition of experimentally induced cough in healthy subjects
  1. E C Young1,
  2. L A Houghton2,
  3. K J Holt1,
  4. A A Woodcock1,
  5. J A Smith1
  1. 1University of Manchester, Manchester, UK
  2. 2Mayo Clinic, Jacksonville, Florida, USA

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:

  • B: Basal-no intervention (both blocks)

  • W: Warm-hand placed in non-painful 32°C water (both blocks)

  • C: Cold-hand placed in painful 10°C or non-painful 32°C water (randomised order)

  • S: Suppression-instructed to “try not to cough” or “cough freely” (randomised order) while placing hand in 32°C warm water.

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) and showed a trend towards a reduction in urge-to-cough (p=0.104) (Abstract S144a figure 1B). Compared to W, S significantly reduced cough (p=0.016) (see Abstract S144a figure 1C) but urge-to-cough did not change (p=0.631) (Abstract S144a figure 1D).

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.

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