Reply to: Noxious cold stimulation: pro–con perspectives on the hypothermic effect on experimentally evoked cough

We thank S. Zhong and co-workers for their interest and thoughtful letter in response to our manuscript, “The effect of pain conditioning on experimentally evoked cough: evidence of impaired endogenous inhibitory control mechanisms in refractory chronic cough” [1]. In this study we demonstrated that a painful cold stimulus, applied to the hand, inhibited cough responses to capsaicin in humans, and that this phenomenon (known as conditioned pain modulation, CPM) was impaired in patients with refractory chronic cough. Interestingly, the recent study performed by Dong et al. [2] also investigated the effects of cold on the cough reflex. They found placing guinea pigs in a cold environment had the opposite effect, heightening cough responses to cinnamaldehyde in animals repeatedly exposed to citric acid; the citric acid exposure being an attempt to emulate the hyperexcitability of the cough reflex observed in patients with chronic cough. Cold-induced pain inhibits cough responses to capsaicin, and this contrasts with the effect of whole-body exposure to cold environments in animal models, which heightens the cough responses to some inhaled irritants. https://bit.ly/2MiZdN2