Topographical differences in distribution and responsiveness of trigeminal sensitivity within the human nasal mucosa.
The study was designed to provide a topographical map of the sensitivity of the human nasal respiratory epithelium towards trigeminal chemosensory stimuli. As an electrophysiological measure of intranasal trigeminal activation at the level of the epithelium, we used the so-called negative mucosa potential (NMP), a measure that represents the sum of generator potentials of trigeminal receptor neurons after chemical stimulation. Sixty subjects participated (30 men and 30 women; mean age 23.5 years). Measurements were made in response to stimulation with menthol, CO(2), ethanol, and cinnamaldehyde, which are known to activate trigeminal receptors to various degrees. Recordings of the NMP were made from five intranasal sites: the anterior septum, the posterior septum, the tip of the middle turbinate, the tip of the lower turbinate, and the lateral side wall of the posterior nasal cavity. The recording electrode was positioned under endoscopic control. The largest NMP amplitudes were recorded at the anterior septum in response to stimulation with CO(2). Comparing all recording sites, significant differences were observed between responses at the posterior septum and the lateral side wall of the posterior nasal cavity in response to stimulation by ethanol, menthol, and CO(2). These findings suggest that the presence of topographical and chemosensory differences in the responsiveness of the nasal mucosa to irritants.
Meusel
Thomas
T
Smell & Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School "Technische Universität Dresden", Dresden, Germany.
Negoias
Simona
S
Scheibe
Mandy
M
Hummel
Thomas
T
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D002245:Carbon Dioxide / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D000432:Methanol / Q000494:pharmacology; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D013223:Statistics as Topic; D013268:Stimulation, Chemical; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
D002245:Carbon Dioxide; D000431:Ethanol; D000432:Methanol
Angell James JE, Daly Mde B. Nasal reflexes. Proc R Soc Med. 1969;62:1287-1293.
Anton F, Peppel P. Central projections of trigeminal primary afferents innervating the nasal mucosa: a horseradish peroxidase study in the rat. Neuroscience. 1991;41:617-628.
Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004;41:849-857.
Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Hogestatt ED, Julius D, Jordt SE, Zygmunt PM. Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci USA. 2005;102:12248-12252.
Berg J, Hummel T, Huang G, Doty RL. Trigeminal impact of odorants assessed with lateralized stimulation. Chem Senses. 1998;23:587.
Cain WS, Murphy CL. Interaction between chemoreceptive modalities of odour and irritation. Nature. 1980;284:255-257.
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389:816-824.
Cometto-Muniz JE, Cain WS. Relative sensitivity of the ocular trigeminal, nasal trigeminal and olfactory systems to airborne chemicals. Chem. Senses. 1995;20:191-198.
Cometto-Muniz JE, Cain WS. Trigeminal and olfactory sensitivity: comparison of modalities and methods of measurement. Int Arch Occup Environ Health. 1998;71:105-110.
Doty RL. Intranasal trigeminal detection of chemical vapors by humans. Physiol Behav. 1975;14:855-859.
Doty RL, Brugger WE, Jurs PC, Orndorff MA, Snyder PJ, Lowry LD. Intranasal trigeminal stimulation from odorous volatiles: psychometric responses from anosmic and normal humans. Physiol Behav. 1978;20:175-185.
Eccles R, Griffiths DH, Newton CG, Tolley NS. The effects of menthol isomers on nasal sensation of airflow. Clin Otolaryngol Allied Sci. 1988;13:25-29.
Eccles R, Lancashire B, Tolley NS. Experimental studies on nasal sensation of airflow. Acta Otolaryngol. 1987;103:303-306.
Frasnelli J, Heilmann S, Hummel T. Responsiveness of human nasal mucosa to trigeminal stimuli depends on the site of stimulation. Neurosci Lett. 2004;362:65-69.
Gerhold KA, Bautista DM. Molecular and cellular mechanisms of trigeminal chemosensation. Ann N Y Acad Sci. 2009;1170:184-189.
Handwerker H, Kobal G. Psychophysiology of experimentally induced pain. Physiol Rev. 1993;73:639-671.
Harkema JR, Carey SA, Wagner JG. The nose revisited: a brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium. Toxicol Pathol. 2006;34:252-269.
Hummel T, Delwiche JF, Schmidt C, Huttenbrink KB. Effects of the form of glasses on the perception of wine flavors: a study in untrained subjects. Appetite. 2003;41:197-202.
Hummel T, Gruber M, Pauli E, Kobal G. Chemo-somatosensory event-related potentials in response to repetitive painful chemical stimulation of the nasal mucosa. Electroen Clin Neurophysiol. 1994;92:426-432.
Hummel T, Livermore A. Intranasal chemosensory function of the trigeminal nerve and aspects of its relation to olfaction. Int Arch Occup Environ Health. 2002;75:305-313.
Hummel T, Mohammadian P, Marchl R, Kobal G, Lotsch J. Pain in the trigeminal system: irritation of the nasal mucosa using short- and long-lasting stimuli. Int J Psychophysiol. 2003;47:147-158.
Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 2004;427:260-265.
Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001;413:203-210.
Kobal G. Pain-related electrical potentials of the human nasal mucosa elicited by chemical stimulation. Pain. 1985;22:151-163.
Kobal G, Hummel C, Nuernberg B, Brune K. Effects of pentazocine and acetylsalicylic acid on pain-rating, pain-related evoked potentials and vigilance in relationship to pharmacokinetic parameters. Agents Actions. 1990;29:342-359.
Kobal G, Van Toller S, Hummel T. Is there directional smelling? Experientia. 1989;45:130-132.
Konstantinidis I. The taste peripheral system. B-ENT. 2009;5:115-121.
Laska M, Distel H, Hudson R. Trigeminal perception of odorant quality in congenitally anosmic subjects. Chem Senses. 1997;22:447-456.
Lee SH, Iwanaga T, Hoshi O, Adachi I, Fujita T. Regional differences of CGRP-immunoreactive nerve fibers in nasal epithelium of the rat. Arch Histol Cytol. 1995;58:117-126.
Lotsch J, Lange C, Hummel T. A simple and reliable method for clinical assessment of odor thresholds. Chem Senses. 2004;29:311-317.
Lundberg JO, Weitzberg E. Nasal nitric oxide in man. Thorax. 1999;54:947-952.
Mackenzie RA, Burke D, Skuse NF, Lethlean AK. Fiber function and perception during cutaneous nerve block. J Neurol Neurosurg Psychiatry. 1975;38:865-873.
Mason JR, Silver WL. Trigeminally mediated odor aversions in starlings. Brain Res. 1983;269:196-199.
McKemy DD, Neuhausser WM, Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. 2002;416:52-58.
Namer B, Seifert F, Handwerker HO, Maihöfner C. TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. NeuroReport. 2005;16:955-959.
Nicoletti P, Trevisani M, Manconi M, Gatti R, De Siena G, Zagli G, Benemei S, Capone JA, Geppetti P, Pini LA. Ethanol causes neurogenic vasodilation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig. Cephalalgia. 2008;28:9-17.
Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A. A TRP channel that senses cold stimuli and menthol. Cell. 2002;108:705-715.
Roos A, Boron WF. Intracellular pH. Physiol Rev. 1981;61:296-434.
Roscher S, Glaser C, Hummel T, Kobal G. An esy method for separating olfactory from trigeminal stimulation. Chem Senses. 1996;21:492.
Scheibe M, van Thriel C, Hummel T. Responses to trigeminal irritants at different locations of the human nasal mucosa. Laryngoscope. 2008;118:152-155.
Scheibe M, Zahnert T, Hummel T. Topographical differences in the trigeminal sensitivity of the human nasal mucosa. NeuroReport. 2006;17:1417-1420.
Sekizawa S, Tsubone H, Kuwahara M, Sugano S. Nasal receptors responding to cold and l-menthol airflow in the guinea pig. Respir Physiol. 1996;103:211-219.
Silver WL, Moulton DG. Chemosensitivity of rat nasal trigeminal receptors. Physiol Behav. 1982;28:927-931.
Sinclair DC, Hinshaw JR. A comparison of the sensory dissociation produced by procaine and by limb compression. Brain. 1950;73:480-498.
Stevens JC, Cain WS. Aging and the perception of nasal irritation. Physiol Behav. 1986;37:323-328.
Szallasi A. The vanilloid (capsaicin) receptor: receptor types and species differences. Gen Pharmacol. 1994;25:223-243.
Thuerauf N, Kaegler M, Dietz R, Barocka A, Kobal G. Dose-dependent stereoselective activation of the trigeminal sensory system by nicotine in man. Psychopharmacology (Berl). 1999;142:236-243.
Thurauf N, Friedel I, Hummel C, Kobal G. The mucosal potential elicited by noxious chemical stimuli with CO2 in rats: is it a peripheral nociceptive event? Neurosci Lett. 1991;128:297-300.
Thurauf N, Hummel T, Kettenmann B, Kobal G. Nociceptive and reflexive responses recorded from the human nasal mucosa. Brain Res. 1993;629:293-299.
Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998;21:531-543.
Torebjork HE, Hallin RG. Perceptual changes accompanying controlled preferential blocking of A and C fibre responses in intact human skin nerves. Exp Brain Res. 1973;16:321-332.
Trevisani M, Smart D, Gunthorpe MJ, Tognetto M, Barbieri M, Campi B, Amadesi S, Gray J, Jerman JC, Brough SJ, Owen D, Smith GD, Randall AD, Harrison S, Bianchi A, Davis JB, Gepetti P. Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1. Nat Neurosci. 2002;5:546-551.
Welge-Lussen A, Wolfensberger M, Kobal G, Hummel T. Basics, methods and indications for objective olfactometry. Laryngorhinootologie. 2002;81:661-667.
Yang BH, Piao ZG, Kim YB, Lee CH, Lee JK, Park K, Kim JS, Oh SB. Activation of vanilloid receptor 1 (VR1) by eugenol. J Dent Res. 2003;82:781-785.