Sulfur-Containing Malodorant Vapors Enhance Responsiveness to the Sensory Irritant Capsaicin

The nose is innervated with both odor responsive olfactory (cranial nerve I) and irritant responsive trigeminal (cranial nerve V) nerves. The nature and extent of any interactions between these two nerves is poorly understood. The aim of the current study was to determine if two sulfur-containing malodorants, ethyl sulfide and t-butyl sulfide, modulated responsiveness to the trigeminal C fiber stimulant capsaicin using female C57Bl/6J mice as an experimental model. Cessation or marked slowing of flow at the onset of each expiration (termed braking) was used as a biomarker for trigeminal nerve stimulation. Aerosolized capsaicin solution (100 μg/ml) increased the time of braking from baseline levels of 8 ms to an average of 69 ms. At an exposure concentration of 100 ppm the malodorants induced only a minimal time of braking response (< 35 ms); the time of braking response in animals exposed to either malodorant plus capsaicin was 2.5-fold greater than in animals exposed to capsaicin alone (p < 0.01). In a subsequent experiment the time of breaking response to capsaicin was doubled (281 vs. 146 ms) by concomitant exposure to a no effect level of ethyl sulfide (11 ppm) and the modulation of capsaicin responsiveness was nearly abolished by inclusion of the adenosine antagonist theophylline in the aerosol formulation (time of braking 184 ms, p ≥ 0.05 compared with capsaicin alone). These results suggest trigeminal nerve responsiveness is enhanced by exposure to malodorants through a theophylline-sensitive paracrine signaling pathway between olfactory and trigeminal nerves.