Recent studies suggest that menthol inhalation (MI) may relieve dyspnea in people with COPD. It was proposed that menthol likely activates cold receptors in the upper airways, which modulate perception of airflow and breathing-related effort. We investigated if dyspnea relief from menthol is related to changes in the neural processing of respiratory sensations in healthy individuals. 

5 healthy adults (60% male, 25±2yrs) performed 2x5min resistive-loaded breathing trials with menthol or placebo (strawberry) deposited into the breathing circuit, in random order. The load was individually titrated to reflect a severe dyspnea intensity level (5 on the 0-10 Borg scale). Ventilatory parameters were measured continuously. Inspiration was interrupted for 150ms every 2-6 breaths to induce a respiratory related-evoked potential (RREP) in the electroencephalogram. The amplitude of the P3 RREP component was used to non-invasively assess cognitive-affective processing of respiratory sensations. Dyspnea intensity and unpleasantness ratings were recorded on the Borg scale after each trial. Trials were separated by 30min.

Ventilation, tidal volume, breathing frequency, and mouth pressure were similar between trials (all p>0.05). P3 amplitude was 38±27% lower with menthol (p=0.03). Dyspnea intensity ratings were not different between trials (3.8±1.9 vs. 4.4±2.2; p=0.25); however, unpleasantness ratings were lower with menthol (3.0±1.6 vs. 4.4±2.3; p=0.03) with a between-condition difference >MCID of 1.

In the absence of change in ventilatory parameters, alteration in the cognitive-affective processing of respiratory sensations seems to contribute to a reduction in dyspnea unpleasantness during MI.