RATIONALE: 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. CONCLUSION: 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.
RCT Entities:
RATIONALE: 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. CONCLUSION: 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.
Authors: Eric C Donny; Rachel L Denlinger; Jennifer W Tidey; Joseph S Koopmeiners; Neal L Benowitz; Ryan G Vandrey; Mustafa al'Absi; Steven G Carmella; Paul M Cinciripini; Sarah S Dermody; David J Drobes; Stephen S Hecht; Joni Jensen; Tonya Lane; Chap T Le; F Joseph McClernon; Ivan D Montoya; Sharon E Murphy; Jason D Robinson; Maxine L Stitzer; Andrew A Strasser; Hilary Tindle; Dorothy K Hatsukami Journal: N Engl J Med Date: 2015-10 Impact factor: 91.245
Authors: Karen Ahijevych; Beverly J Tepper; Margaret C Graham; Christopher Holloman; William A Matcham Journal: Nicotine Tob Res Date: 2014-12-26 Impact factor: 4.244
Authors: Thomas E Taylor-Clark; Filmawit Kiros; Michael J Carr; M Allen McAlexander Journal: Am J Respir Cell Mol Biol Date: 2008-12-04 Impact factor: 6.914