The inflammatory molecule sphingosine-1-phosphate is not effective to evoke or sensitize cough in naïve guinea pigs.

Sphingosine-1-phosphate (S1P) is an inflammatory mediator increased in the tissue in the number of inflammatory conditions. Preliminary data indicate that the vagal afferent neurons express several S1P receptors including S1PR2-3. We therefore evaluated the hypothesis that S1P induces cough and/or enhances the cough evoked by other tussive stimuli (TRPA1 and TRPV1 activators) in naïve guinea pigs. Inhalation of S1P in the concentrations of 0.1 mM and 1 mM did not evoke cough. Preinhalation and continuing inhalation of S1P (1 mM) during citric acid (0.2 M) challenge did not enhance citric acid-induced cough. Preinhalation of S1P and continuing inhalation during AITC (3 mM) challenge also did not enhance AITC-induced cough. We conclude that S1P was not efficient to evoke cough in awake naïve guinea pigs. S1P was also not effective to sensitize the cough evoked by stimulation of TRPV1 and TRPA1 receptors. Nonetheless it cannot be excluded that S1P influences cough in the context of inflamed airways when the cough-mediating nerves undergo sensory neuroplasticity.