Dose-dependent stereoselective activation of the trigeminal sensory system by nicotine in man.
BACKGROUND
Nicotine applied to the nasal cavity can evoke 'odorous' sensations in the concentration range near the detection threshold by the activation of the olfactory sensory system and at higher concentrations 'burning' and 'stinging' sensations by the dose-dependent recruitment of C- and Adelta-fibers of the trigeminal sensory system. Neuronal nicotinic acetylcholine receptor (nAchR) subunits are expressed in trigeminal primary afferents and could constitute the receptors involved in nicotine perception.


OBJECTIVE
In the present study, we dose-dependently investigated the stereoselective effects of R(+)- and S(-)-nicotine on the trigeminal and olfactory sensory system in man.


METHODS
Trigeminal detection thresholds for the 'burning' and 'stinging' sensations and the olfactory detection threshold for the 'odorous' sensation were determined. In order to quantify trigeminal activation, we recorded summated electrical responses from the respiratory nasal mucosa during stimulation with R(+)-and S(-)-nicotine vapor (40, 80, 120, 160 ng/ml; stimulus duration: 250 ms). In addition, subjects rated the intensity of 'odorous', 'burning' and 'stinging' sensations. For chemical stimulation with nicotine enantiomers, a vapor-dilution olfactometer (constant flow rate: 140 ml/s, humidity: 80%, temperature: 37 degrees C, stimulus duration 250 ms) was employed.


RESULTS
We found significant stereoselective differences for the trigeminal but not for the olfactory system, i.e. higher summated responses, higher trigeminal intensity estimates, and lower trigeminal detection thresholds for S(-)- compared to R(+)-nicotine.


CONCLUSIONS
Our results clearly demonstrate the different stereoselective activation of the trigeminal sensory system by R(+)-and S(-)-nicotine, indicating the presence of specific stereoselective receptors on trigeminal nociceptive Adelta- and C-fibers.
Thuerauf
N
N
Psychiatrische Klinik der Universität Erlangen-Nürnberg, Erlangen, Germany.
Kaegler
M
M
Dietz
R
R
Barocka
A
A
Kobal
G
G
D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D012684:Sensory Thresholds / Q000187:drug effects*; D013237:Stereoisomerism; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000502:physiology
D018722:Nicotinic Agonists; D009538:Nicotine