Menthol inhalation relieves dyspnoea through the brain.

Background: Menthol inhalation (MI) relieves dyspnoea in healthy individuals and people with respiratory disorders, independent of changes in breathing patterns and respiratory muscle electromyography activity. Thus, the underlying working mechanism of MI is unknown. We tested whether MI reduces dyspnoea by attenuating the neural processing of afferent respiratory sensations, without altering respiratory patterns and the efferent neural drive to breathe. Methods: Thirty healthy adults completed four 5-min trials of strong inspiratory resistive loaded breathing: two with MI and two with strawberry scent inhalation (SI; placebo control), in counterbalanced order. Paired inspiratory occlusions (150 ms) were randomly administered every 2-6 breaths to evoke respiratory-related evoked potentials (RREPs) in the electroencephalogram, reflecting neural processing of respiratory signals. Respiratory parameters were measured continuously, and neural drive to breathe was assessed Results: Dyspnoea intensity (Δ=-0.67 modified Borg units, p=0.003, d=-0.56), air hunger (p<0.001), and mental breathing effort (p=0.004) were lower with MI compared with SI. The RREP P2 mean amplitude was lower with MI (Δ=-1.51 µV, p=0.04, d=0.38), and exploratory analysis revealed an additional reduced "P3frontal" RREP component (p=0.04). Respiratory parameters and P0.1 showed only minor differences between conditions. Conclusions: MI relieved dyspnoea with concurrent changes in the neural processing of respiratory sensations, in the absence of meaningful changes in respiratory patterns or neural drive to breathe. This suggests that MI relieves dyspnoea