Impact of trigeminal nerve and/or olfactory nerve stimulation on activity of human brain regions involved in the perception of breathlessness

Breathlessness is a centrally processed symptom, as evidenced by activation of distinct brain regions such as the insular cortex and amygdala, during the anticipation and/or perception of breathlessness. Inhaled L-menthol or blowing cool air to the face/nose, both selective trigeminal nerve (TGN) stimulants, relieve breathlessness without concurrent improvements in physiological outcomes (e.g., breathing pattern), suggesting a possible but hitherto unexplored central mechanism of action. Four databases were searched to identify published reports supporting a link between TGN stimulation and activation of brain regions involved in the anticipation and/or perception of breathlessness. The collective results of the 29 studies demonstrated that TGN stimulation activated 12 brain regions widely implicated in the anticipation and/or perception of breathlessness, including the insular cortex and amygdala. Inhaled L-menthol or cool air to the face activated 75% and 33% of these 12 brain regions, respectively. Our findings support the hypothesis that TGN stimulation contributes to breathlessness relief by altering the activity of brain regions involved in its central neural processing.