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ToxSci Advance Access originally published online on March 28, 2008
Toxicological Sciences 2008 104(1):198-209; doi:10.1093/toxsci/kfn061
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

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

Christopher R. DeSesa, Ryan P. Vaughan, Michael J. Lanosa, Kathryn G. Fontaine and John B. Morris1

Toxicology Program, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269

1 To whom correspondence should be addressed at Toxicology Program, Department of Pharmaceutical Sciences, 69 N. Eagleville Rd, U-3092, University of Connecticut, Storrs, CT 06269-3092. Fax: (860) 486-5792. E-mail: john.morris{at}uconn.edu.

Received February 7, 2008; accepted March 13, 2008


  Abstract

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.

Key Words: sensory irritation; inhalation toxicology; volatile organic compound.


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