Intranasal Trigeminal Function Research Articles

Assessment of Intranasal Function of the Trigeminal Nerve in Daily Clinical Practice

<b><i>Background:</i></b> The trigeminal nerve is a mixed cranial nerve responsible for the motor innervation of the masticatory muscles and the sensory innervation of the face, including the nasal cavities. Through its nasal innervation, we perceive sensations, such as cooling, tingling, and burning, while the trigeminal system mediates the perception of airflow. However, the intranasal trigeminal system has received little attention in the clinical evaluation of patients with nasal pathology. <b><i>Summary:</i></b> Testing methods that enable the clinical assessment of intranasal trigeminal function have recently been developed. This study aims to present the current clinical methods that can be utilised in everyday practice, as described in the literature. These methods include four assessment techniques: (1) the quick screening test of trigeminal sensitivity involves patients rating the intensity of ammonium vapour presented in a lipstick-like container. (2) The lateralisation test requires subjects to identify which nasal cavity is being stimulated by a trigeminal stimulus, such as eucalyptol or menthol, while the other side receives an odourless stimulus. (3) The trigeminal sticks test evaluates the trigeminal function similarly to the olfactory function using sticks filled with trigeminal stimulant liquids. (4) The automated CO<sub>2</sub> stimulation device is used for measuring trigeminal pain thresholds, utilising intranasal CO<sub>2</sub> stimuli to define the pain threshold. <b><i>Key Messages:</i></b> Assessing intranasal trigeminal function clinically may prove useful in evaluating rhinology patients, particularly those who encounter nasal obstruction without anatomical blockage and those experiencing olfactory disorders with suspected trigeminal dysfunction. Despite their limitations, the presented methods may provide useful information about nasal patency, chemosensitivity, and pain sensation in the daily clinical practice of such patients, leading to better therapeutic decisions.

Trigeminal cold receptors and airflow perception are altered in chronic rhinosinusitis.

In chronic rhinosinusitis (CRS), nasal obstruction can often be explained by anatomical deformities, polyps, or congested nasal mucosa. However, in cases with little deformity or inflammation, perceived nasal obstruction may result from reduced airflow perception caused by an alteration of the intranasal trigeminal system. The aim of this study was to assess this association. We performed a prospective case-control study of 15 CRS patients, 18 patients with a deviated nasal septum (DNS) and 16 healthy controls. We assessed olfactory function using the Sniffin' Sticks test and Visual Analog Scales (VAS). We used the Trigeminal Lateralization Task (TLT) with eucalyptol and cinnamaldehyde to examine intranasal trigeminal function. Further, we assessed nasal patency with Peak Nasal Inspiratory Flow and VAS. Finally, we measured protein levels of trigeminal receptors (TRPM8, TRPA1 and TRPV1) and inflammatory markers (IL-13, INF-y and eosinophils) in CRS and DNS patients' mucosal biopsies using Western Blots. CRS patients had significantly lower olfactory function than DNS and healthy controls. They also had significantly lower TLT scores for eucalyptol than both other groups. CRS patients had significantly lower nasal patency than controls; for DNS patients this was limited to subjective measures of nasal patency. In line with this, CRS patients exhibited significantly higher levels of sTRPM8-18 than DNS patients. Intranasal trigeminal function is decreased in CRS patients, possibly due to the overexpression of short isoforms of TRPM8 receptors.

Trigeminal function in patients with COVID-associated olfactory loss.

Olfactory dysfunction (OD) can be a long-term consequence of various viral infections, including COVID-19. Dysfunction includes hyposmia/anosmia and parosmia (odor distortions). Interactions of the virus with the olfactory nerve have been extensively researched, but little is known about the interactions of the intranasal trigeminal nerve system in modulating this sensory loss. We investigated intranasal trigeminal function across COVID-19 OD patients with and without parosmia compared to normosmic controls, to determine whether (1) post-viral hyposmia and/or (2) post-viral hyposmia with parosmia is associated with altered trigeminal function. OD patients (n = 27) were tested for olfactory function using the extended Sniffin' Sticks olfactory test and for trigeminal function through three methods-odor lateralization, subjective ratings of nasal patency, and ammonium vapor pain intensity ratings. This group was subsequently compared to controls, normosmic subjects (n = 15). Our findings revealed that post-COVID OD patients without parosmia experienced decreased sensitivity in ammonium vapor pain intensity ratings and odor lateralization scores-but similar nasal patency ratings-compared to normosmic controls. There were no significant differences in trigeminal function between OD patients with and without parosmia. Based on our results, we conclude that the trigeminal nerve dysfunction may partially explain post-viral OD, but does not seem to be a major factor in the generation of parosmia pathophysiology.

Unique Measurements of Intranasal Trigeminal Function: A Pilot Study.

To investigate novel methods of measuring intranasal trigeminal function and correlate to validated measures of trigeminal function. Prospective cohort study. Tertiary medical center. Forty-one subjects without nasal congestion were assessed. The trigeminal temperature function of the cool/warmth detection threshold and cold/heat pain threshold was measured with the Thermal Sensory Analyzer (TSA) device, as previously validated at buccal mucosa and infraorbital skin. Identical temperature sensory function was assessed at the anterior septum and inferior turbinate. Lateralization of trigeminal odorants eucalyptol, isothiocyanate, and acetic acid was conducted. Visual analog scales (VAS) of trigeminal function were collected. Extraoral cheek site and oral site thermal measures were moderately correlated, suggesting consistent assessment of trigeminal function. Nearly all intranasal thermal measures correlated between the septum and turbinate (significant correlations [ρ] ranged from .3 to .8). Oral and extraoral cheek sites had modest correlations to intranasal cold and heat pain (ρ = .4-.5). The oral site had modest correlations of cold and heat detection to intranasal sites, with turbinate appearing to have the most correlations. Isothiocyanate lateralization was the most closely correlated to intranasal thermal scores for cold and heat pain. Turbinate thermal measures had weak correlations with trigeminal VAS scores (ρ = .3-.4). Intranasal trigeminal measures of thermal function correlate to validated extraoral and intraoral thermal measures. The turbinate appears to have stronger correlations to the septum than found in the mouth and face. TSA testing might provide a rapid, novel method of intranasal trigeminal function assessment.

Intranasal trigeminal sensitivity may be impaired after functional nasal surgery

Functional nasal surgery is frequently performed for sinonasal diseases not responding to medical treatment. Although surgery mostly turns out to be successful in such cases, a potential side effect of manipulating the nasal mucous membrane is impairment of intranasal trigeminal function. Not well known by specialists and clinically scarcely explored, this function provides sensory information from the nasal mucosa. It is responsible for the afferent part of protective nasal reflexes such as sneezing and coughing, but also provides the feeling of nasal airflow (1). Recent work suggests that patients with low intranasal trigeminal function are more prone to suffer from nasal obstruction and may be less satisfied with functional surgery (2-6). It has been suggested that intranasal trigeminal function decreases with mucosal changes, such as chronic inflammation and improves again once the inflammation has been treated (3). However, the influence of functional nasal surgery (i.e. surgery aimed at the improvement of nasal function) with consecutive mucosal micro-injuries on intranasal trigeminal function is not yet fully clear (2-4).

Rhinology in review: from COVID-19 to biologicals

We look back at the end of what soon will be seen as an historic year, from COVID-19 to real-world introduction of biologicals influencing the life of our patients. This review describes the important findings in Rhinology over the past year. A large body of evidence now demonstrates loss of sense of smell to be one of the most common symptoms of COVID-19 infection; a meta-analysis of 3563 patients found the mean prevalence of self-reported loss to be 47%. A number of studies have now shown long-term reduced loss of smell and parosmia. Given the high numbers of people affected by COVID-19, even with the best reported recovery rates, a significant number worldwide will be left with severe olfactory dysfunction. The most prevalent causes for olfactory dysfunction, besides COVID-19 and upper respiratory tract infections in general, are trauma and CRSwNP. For these CRSwNP patients a bright future seems to be starting with the development of treatment with biologics. This year the Nobel prize in Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch which has greatly enhanced our understanding of nasal hyperreactivity and understanding of intranasal trigeminal function. Finally, a new definition of chronic rhinitis has been proposed in the last year and we have seen many papers emphasizing the importance of endotyping patients in chronic rhinitis and rhinosinusitis in order to optimise treatment effect.

Trigeminal impairment in treatment-refractory chronic nasal obstruction.

Patients with anatomically unexplained, chronic nasal obstruction (CNO) that is refractory to medical treatment pose a challenge for clinicians. A surgical solution, addressing mechanical obstacles, is unsuited for these patients. CNO may result from disrupted airflow perception due to activation of the intranasal trigeminal system; therefore, aim of this study is to evaluate if intranasal trigeminal function of these CNO patients is decreased. In this retrospective cross-sectional study, we compared 143 CNO patients and 58 healthy volunteers, between 18 to 80 years old. We assessed nasal patency by means of rhinomanometry (RM) and measured susceptibility of intranasal trigeminal system by the trigeminal lateralization task (TLT). TLT scores were significantly lower in CNO patients compared to controls (p less than 0.001), but RM scores were not different between groups. Accordingly, TLT allowed to identify CNO patients with an accuracy of the area under the curve (AUC) of 0.78, while the value for RM was at chance (AUC=0.47). CNO patients showed normal reaction to vasoconstrictive agents with significantly lower RM values after Xylomethazoline application. Results suggest that reported nasal obstruction in CNO patients without any obvious anatomical obstacle and resistant to medical treatment may be linked to decreased perception of nasal airflow rather than physical obstruction. In this sub-set of CNO patients, trigeminal testing more adequately reflects the reported obstruction than nasal resistance assessment does. In future studies, the relation of the trigeminal status and the subjective sensation of nasal obstruction needs to be addressed with validated patient rated outcome measures (PROMs).

Multisensory environmental sensitivity in patients with chronic tinnitus

ObjectiveThe study aimed at investigating the sensitivity to noise and chemosensory environmental stressors as well as the relation to perceived stress, depression and anxiety in subjects with chronic tinnitus as compared to subjects without tinnitus. MethodsWe included 75 subjects with chronic tinnitus and 75 age and sex-matched subjects without tinnitus. Standardized questionnaires assessing the level of distress and impairment of quality of life caused by tinnitus, perceived level of stress, anxiety and depression, environmental noise and chemosensory sensitivity were used. A subgroup of 27 subjects with chronic tinnitus and 20 age-matched subjects without tinnitus underwent testing of olfactory function with the Sniffin’ Sticks test and testing of intranasal trigeminal function using CO2 thresholds. ResultsOur data confirmed the increased environmental noise sensitivity (NSS) in patients with tinnitus. Furthermore, we observed an increased environmental chemosensory sensitivity (CSS), but no difference in measured chemosensory function. Subjects with tinnitus showed also significant higher levels of perceived stress, anxiety and depression and those symptoms partially correlated to CSS and NSS. Predictors of both NSS and CSS results were the presence / absence of tinnitus and high anxiety levels while neither stress nor depression were found as predicting variables. ConclusionsThe results suggest that chronic tinnitus is related to a multisensory environmental hypersensitivity. Anxiety seems to be a predictor of this environmental vulnerability.

Determinants and Evaluation of Nasal Airflow Perception.

AbstractThe sensation of nasal airflow, or nasal airway patency, is an important consideration in the treatment outcome of nasal airway obstruction. Clinicians striving to optimize the nasal passageway have relied on techniques aimed at decreasing peak airway resistance across nasal valves. Nonetheless, the evaluation of the nasal airway is multifaceted, and the objective determinants of subjective nasal patency remain incompletely elucidated. While rhinomanometry, peak nasal inspiratory airflow, and acoustic rhinometry have traditionally been used in research to focus on resistance as a measure of patency, an emerging body of evidence suggests that subjective nasal patency is more significantly correlated to the dynamic change of nasal mucosal temperature. The objective of this review is to provide the technical background on nasal airflow perception and intranasal trigeminal function as crucial to those performing functional and aesthetic rhinosurgery.

Intranasal trigeminal function in patients with empty nose syndrome.

Trigeminal nerve mediates the perception of nasal airflow. This study examines whether impaired intranasal trigeminal function is a part of the paradoxical nasal obstruction sensation in patients with empty nose syndrome (ENS). Prospective case-control study in a tertiary hospital. Three groups were examined: 1) ENS patients with previous bilateral near total inferior turbinectomy, 2) patients who underwent near total inferior turbinate removal (ITR) without ENS symptoms, and 3) control participants. All participants examined with active anterior rhinomanometry, olfactory testing (extended Sniffin' Sticks test), and trigeminal testing (lateralization task using menthol and odorless solvent). Seventy-one participants were included (21 ENS patients, 18 ITR patients, and 31 controls). Analyses revealed that ENS patients had significantly lower scores on trigeminal lateralization testing than the ITR group and controls. The ENS group had also significantly lower scores in olfactory testing than controls. No statistical differences were found in rhinomanometry between groups. The gender factor was not associated with the chemosensory testing; however, this was not the case with the age factor, as trigeminal test results were negatively correlated. This study demonstrates significantly impaired intranasal trigeminal function in ENS patients when compared with ITR patients and controls. Further prospective studies are needed to clarify the role of preoperative trigeminal function of these patients and the contribution of surgery to this impairment. 3b. Laryngoscope, 127:1263-1267, 2017.

Automated assessment of intranasal trigeminal function

The intranasal trigeminal system is a key player in the perception of intranasal airflow. Why it has not been studied very well may be due to the lack of techniques that allow for fast, reliable and inexpensive routine investigation of the system. The basis of the current study is the notion that--within limits--the intranasal trigeminal system detects the overall mass of a stimulus and not just its concentration. Thus, changing the duration of the stimulus at a given concentration has a similar effect as changing its concentration. Ninety-nine normosmic subjects participated [48 women and 51 men; mean (range) age = 45 years (20-88 years)]. In addition, 50 patients with olfactory loss were investigated once (28 women, 22 men; mean age 58 years, SD = 14 years; age range 24-88 years; causes of olfactory loss: viral infections n = 22, head trauma n = 8, chronic sinunasal disease n = 3, idiopathic n = 17). CO2-stimuli with various durations (multiples of 50 ms) were presented through a standard bilateral nasal cannula at an interval of 10 s; stimulus duration was increased by 50 ms from one stimulus presentation to the next, until the subject pushed a button indicating a painful sensation. This was the basis for automated assessment of CO2-pain responsiveness. This current study had four main findings: (1) Using the new, automated device CO2 pain responsiveness can be measured reliably, (2) CO2 pain responsiveness correlates with olfactory function, (3) as with olfaction, women are more sensitive to CO2 , and CO2-pain responsiveness also correlates with aging, (4) CO2-pain responsiveness is lower in patients with olfactory loss compared to normosmic, healthy controls, even when controlling for age. We have demonstrated that the current approach is a reliable and valid measure of intranasal trigeminal function.

A Novel Device for the Clinical Assessment of Intranasal Trigeminal Sensitivity

Despite the significance of trigeminal pathology, practical clinical tests that accurately evaluate intranasal trigeminal function are scarce. The aim of the present study is to introduce a practical procedure for the assessment of intranasal trigeminal sensitivity. We developed a device to stimulate the nasal mucosa using carbon dioxide, which is self-administered intranasally by holding down a timed button until the required sensory response has been triggered. The trigeminal sensitivity is derived from the measured administration time in conjunction with the concentration of carbon dioxide administered. Sixty-three healthy participants were used to validate the device, after which the new device was compared with a standard lateralization task in an additional 16 participants. In 20 participants, the experiment was repeated to verify test-retest reliability. Statistical analysis showed significant consistency in administration-duration in healthy individuals, including those in the test-retest group. Those participants with higher scores in the lateralization task were found to show higher intranasal sensitivity measured by the new device. Herein, we present the design and validation of a novel device for the practical assessment of intranasal trigeminal sensitivity. In this study, we demonstrate the efficacy and reliability of this device.

Chemosensory function in Wegener’s granulomatosis: a preliminary report

Despite the fact that Wegener's granulomatosis affects the nasal and paranasal cavities and the cranial nerves regularly, chemosensory impairments have not been reported. The objective of this study is to test the three chemosensory systems, olfaction, taste, and intranasal trigeminal function in Wegener disease patients. We tested olfactory, gustatory, and intranasal trigeminal function in nine patients (5 women, 4 men, mean age 57 years) with confirmed Wegener's granulomatosis. Olfaction was tested with the Sniffin'Sticks, gustatory function with the "Taste strips" and intranasal trigeminal function with a lateralization task. One patient had anosmia (11%), four patients had hyposmia (44%) and four patients were normosmic (45%). Gustatory testing function showed pathological taste strip results in five patients (55%) and normal results in three patients (33%). One patient did not undergo taste testing. Intranasal trigeminal function was lowered in five patients (56%) and normal in four patients (44%). Neither previous nasal surgery status nor endoscopic status was associated to a higher frequency in pathological scores for any of the three chemical senses. In conclusion, these preliminary results suggest a consistent affection in chemosensory functions in Wegener's granulomatosis patients.

New Whiffs About Chemesthesis. Focus on “TRPM5-Expressing Solitary Chemosensory Cells Respond to Odorous Irritants”

EDITORIAL FOCUSNew Whiffs About Chemesthesis. Focus on “TRPM5-Expressing Solitary Chemosensory Cells Respond to Odorous Irritants”Anna Menini, and Simone PifferiAnna Menini, and Simone PifferiPublished Online:01 Mar 2008https://doi.org/10.1152/jn.00043.2008This is the final version - click for previous versionMoreSectionsPDF (37 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat In the recent article by Lin and collaborators (2008), they show that solitary chemosensory cells dispersed in the respiratory epithelium of the mouse nasal cavity could comprise a new transduction system for some noxious stimuli. Chemical sensitivity in the nasal cavity is not limited to smelling odorants but extends to reacting to irritating stimuli eliciting sensations such as irritation, tickling, burning, stinging, warming, and cooling. These latter sensations are not mediated by the olfactory nerve but by the trigeminal nerve that also innervates the nasal cavity. It has been assumed for a long time that chemical irritants directly act on free nerve endings (for review, see Bryant and Silver 2000; Doty et al. 1978). Sensations arising from chemical irritants are components of the “common chemical sense” (Parker 1912), later named chemesthesis (Green et al. 1990). While the most effective chemesthetic stimuli, lipophilic molecules, diffuse through cell membranes to reach sensory nerve fibers directly, it is less clear how hydrophilic compounds stimulate free nerve endings buried within the epithelial layer. This puzzle has now been solved by the finding that solitary chemosensory cells within the nasal epithelium directly respond to high concentrations of odorant molecules, including hydrophilic ones (Lin et al. 2008).Solitary chemosensory cells, located in the anterior respiratory epithelium of the nasal cavity of rodents, express T2R “bitter-taste” receptors and α-gustducin, a G protein α subunit expressed in taste receptor cells (Finger et al. 2003). Moreover, Kaske et al. (2007) have shown that in the mouse nasal epithelia, there are solitary chemosensory cells expressing TRPM5, a calcium-activated nonselective cation channel belonging to the large family of transient receptor potential channels that plays a fundamental role in taste transduction (Perez et al. 2002; Zhang et al. 2003). Lin et al. (2008) confirmed the presence of solitary chemosensory cells expressing TRPM5 using transgenic mice in which the expression of green fluorescent protein is under the control of TRPM5 promoter. They found a population of ∼11,200 solitary chemosensory cells expressing TRPM5 in the respiratory epithelium especially concentrated near the entry of the nasal cavity. These cells are elongated with an apical process that reaches the luminal surface. They lack any detectable axonal process and have morphological features similar to those of α-gustducin-positive solitary chemosensory cells. However, Lin et at. (2008) showed that some, but not all, TRPM5-expressing cells also express α-gustducin, indicating that the nasal respiratory epithelium contains solitary cells with different sensory properties. Further the authors found that several TRPM5-expressing cells express components of the PLC pathway, such as PLCβ2 and γ13, that in taste receptor cells are involved in the activation of TRPM5 (Liman 2007). However, some cells did not express PLCβ2 and γ13, further evidence for multiple mechanisms of transduction.But do these solitary cells connect to the nervous system? The authors confirmed and extended previous ultrastructural studies by Finger et al. (2003) showing that peptidergic nerve fibers, stained with PGP9.5 or with substance P, closely appose solitary chemosensory cells, running along the length of the cells or wrapping their basal region. This organization would allow sensory signal transmission to trigeminal fibers, perhaps through synaptic transmission. Indeed Lin et al. (2008) found immunoreactivity for synaptobrevin-2 in the same cells indicating that they may transmit sensory information onto nerve fibers through synaptic transmission.What about the functional role of the TRPM5-expressing solitary chemosensory cells? Two types of approaches were used by Lin et al. (2008): electrophysiological recordings from areas containing these cells and Ca2+ imaging recordings from dissociated cells. In the first set of functional experiments, the authors measured local field potentials (event-related potentials) (Hummel 2000; Rombaux et al. 2006) on stimulation of various odorants such as citral, lilial, butanone, or menthone and obtained significant responses only with high concentrations (1–5 mM), in agreement with the well-known low sensitivity to odorants of the trigeminal system (Bryant and Silver 2000; Doty et al. 1978). Control experiments indicated that the responses were due to the activation of the trigeminal system, but both free nerve endings and the cells under study could contribute to the measured local field potentials. Do TRPM5-expressing solitary chemosensory cells respond to irritants? To answer this question, the authors performed Ca2+ imaging experiments on dissociated cells and measured an increase in intracellular Ca2+ concentration in response to chemical stimuli at high concentrations, thus providing the first direct demonstration that solitary chemosensory cells respond to odorous irritants. It is also of interest to note that most cells responded to multiple, but not all, stimuli tested, suggesting that they may be selectively tuned, albeit broadly so.These new findings indicate the existence of heterogenous populations of specialized solitary chemosensory cells in the nasal respiratory epithelium that may bind potentially irritant or harmful chemicals and, through activation of transduction cascades, activate the trigeminal system. Future studies will have to establish the physiological role that solitary chemosensory cells play in nasal chemesthesis and identify the subpopulation profile of these cells, their signal transduction cascades, adaptation properties, and their interplay with direct activation of free nerve endings by lipophilic compounds.REFERENCESBryant and Silver 2000 Bryant B, Silver WL. Chemesthesis. The common chemical sense. In: The Neurobiology of Taste and Smell (2nd ed.), edited by Finger TE, Silver WL, Resprepo D. New York:Wiley-Liss, 2000 p. 73–100.Google ScholarDoty et al. 1978 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 20: 175–185, 1978.Crossref | PubMed | ISI | Google ScholarFinger et al. 2003 Finger TE, Bottger B, Hansen A, Anderson KT, Alimohammadi H, Silver WL. Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc Natl Acad Sci USA 100: 8981–8986, 2003.Crossref | PubMed | ISI | Google ScholarGreen et al. 1990 Green BG, Mason JR, Kare MR. Chemical Senses. Irritation. New York: Marcel Dekker, 1990, vol. 2.Google ScholarHummel 2000 Hummel T. Assessment of intranasal trigeminal function. Int J Psychophysiol 36: 147–155, 2000.Crossref | PubMed | ISI | Google ScholarKaske et al. 2007 Kaske S, Krasteva G, Konig P, Kummer W, Hofmann T, Gudermann T, Chubanov V. TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells. BMC Neurosci 8: 49, 2007.Crossref | PubMed | ISI | Google ScholarLiman 2007 Liman ER. TRPM5 and taste transduction. Handb Exp Pharmacol 287–298, 2007.PubMed | Google ScholarLin et al. 2008 Lin W, Ogura T, Margolskee RF, Finger TE and Restrepo D. TRPM5-expressing solitary chemosensory cells respond to odorous irritants. J Neurophysiol doi:10.1152/jn.01195.2007.Link | ISI | Google ScholarParker 1912 Parker GH. The relations of smell, taste, and the common chemical sense in vertebrates. J Acad Natl Sci Philadelphia 18: 221–234, 1912.Google ScholarPerez et al. 2002 Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF. A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5: 1169–1176, 2002.Crossref | PubMed | ISI | Google ScholarRombaux et al. 2006 Rombaux P, Mouraux A, Bertrand B, Guerit JM, Hummel T. Assessment of olfactory and trigeminal function using chemosensory event-related potentials. Neurophysiol Clin 36: 53–62, 2006.Crossref | PubMed | ISI | Google ScholarSbarbati and Osculati 2003 Sbarbati A, Osculati F. Solitary chemoreceptor cells in mammals? Cell Tissues Organs 175: 51–55, 2003.Crossref | PubMed | ISI | Google ScholarZhang et al. 2003 Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112: 293–301, 2003.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: A. Menini, International School for Advanced Studies, Basovizza, S.S. 14 km 163.5, 34012, Trieste, Italy (E-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByCholinergic microvillous cells in the mouse main olfactory epithelium and effect of acetylcholine on olfactory sensory neurons and supporting cellsTatsuya Ogura, Steven A. Szebenyi, Kurt Krosnowski, Aaron Sathyanesan, Jacqueline Jackson, and Weihong Lin1 September 2011 | Journal of Neurophysiology, Vol. 106, No. 3 More from this issue > Volume 99Issue 3March 2008Pages 1055-1056 Copyright & PermissionsCopyright © 2008 by the American Physiological Societyhttps://doi.org/10.1152/jn.00043.2008PubMed18199823History Published online 1 March 2008 Published in print 1 March 2008 Metrics Downloaded 162 times

Intranasal trigeminal function in children

The aim of the study was to investigate trigeminal function in children compared with that of adults. Trigeminal sensitivity was assessed using a lateralization task where participants were requested to identify the side of the nose to which an odorous stimulus was presented. The ability to localize the sensation is largely based on trigeminal function. A total of 344 people participated (191 females, 153 males; mean age 12 y [SD 7 y 9 mo], range 5-54 y). Eucalyptol (EUC) was administered as a mixed olfactory-trigeminal stimulant; phenylethyl alcohol (PEA) was used as a control stimulant with minimal trigeminal impact. In addition, sensitivity to vibration was assessed as a somatosensory control. With regard to all age groups, PEA could not be localized whereas this was easily possible for EUC. However, the ability to localize EUC increased with age, which was not the case for PEA. No sex-related difference was found for odour localization. These results provide data for normal intranasal trigeminal function in children. They also indicate that trigeminal sensitivity is already well-developed in children.

Intranasal trigeminal function in subjects with and without an intact sense of smell

The intranasal trigeminal system is involved in the perception of odors. To investigate the cerebral processing of sensory information from the trigeminal nerve in detail we studied subjects with and without olfactory function using functional magnetic resonance imaging. A normosmic group ( n = 12) was compared with a group of anosmic subjects ( n = 11). For trigeminal stimulation gaseous CO 2 was used. Following right-sided stimulation with CO 2 controls exhibited a stronger right-sided cerebral activation than anosmic subjects. Stronger activation was found in controls compared to anosmic subjects for the right prefrontal cortex, the right somatosensory cortex (SI), and the left parietal insula. In contrast, relatively higher activation was found in anosmic subjects for the left supplementary motor area in the frontal lobe, the right superior and middle temporal lobe, the left parahippocampal gyrus in the limbic lobe, and the sub-lobar region of the left putamen and right insula which was mostly due to a decreased BOLD signal of controls in these areas. Additional conjunction analysis revealed that activated areas common to the two groups were the cerebellum and the right premotor frontal cortex. These data suggest that the processing of the trigeminally mediated information is different in the presence or absence of an intact sense of smell, pointing towards the intimate connection between the two chemosensory systems.

Chemosensory event-related potentials in relation to side of stimulation, age, sex, and stimulus concentration

Objective For chemosensory event-related potentials (ERP) significant effects of age and sex have been demonstrated. The aim of the present study was to assess the effects of stimulus concentration, side of stimulation, and sex on the topographical distribution of chemosensory ERP in a large group of subjects stratified for different age groups. In addition, psychophysical measures of both olfactory and trigeminal function should be assessed in greater detail compared to previous work. Methods A total of 95 healthy subjects participated in the study. Olfactory functions were tested using the ‘Sniffin' Sticks’ comprising tests of odor identification, odor discrimination, and odor threshold. Trigeminal sensitivity was assessed on a psychophysical level using a lateralization paradigm. ERP to the olfactory stimulant H 2S and the trigeminal irritant CO 2 were recorded; stimuli were presented in different concentrations to the left and right nostril. Results Olfactory thresholds exhibited an age-related increase while the outcome of psychophysical trigeminal tests was not significantly affected by age. In contrast, there was no significant main effect of the factor ‘sex’ for olfactory tests, while women scored higher than men in the trigeminal task. ERP to olfactory and trigeminal stimuli exhibited a relationship to stimulus concentration, age, and sex with youngest women showing largest amplitudes and shortest latencies. There was no significant main effect of left- or right-sided stimulation on ERP. Measures of olfactory function were found to correlate with parameters of olfactory ERP even when controlling for the subject's age. In addition, correlations between scores in the lateralization task and parameters of the trigeminal ERP were found. Conclusions Based on electrophysiological data obtained in a large sample size the present results established an age-related loss of olfactory and trigeminal function, which appears to be almost linear. Further, the present results emphasize that responses to chemosensory stimuli are related to sex, while the side of stimulation does not play a major role in the presently used paradigm. Finally, these data establish the lateralization paradigm as a psychophysical tool to investigate intranasal trigeminal function. Significance The present results obtained in a representative group of healthy subjects establishes a comprehensive set of data, which will serve as reference for future work in this area of research.

Decreased Trigeminal Sensitivity in Anosmia

The present study aimed to investigate intranasal trigeminal sensitivity in a large sample of patients with anosmia due to different etiologies. We investigated the trigeminal detection threshold for formic acid in healthy controls (n = 96) and patients with anosmia due to head trauma (n = 18) or sinonasal disease (n = 54). Anosmics exhibited higher thresholds compared with normosmics (p < 0.001). In addition, thresholds were found to be higher in patients with posttraumatic anosmia compared to anosmics with sinonasal disease (p < 0.001). The data indicate that (1) loss of olfactory sensitivity in humans may be associated with a decreased sensitivity towards trigeminal stimuli and (2) alteration of intranasal trigeminal function is stronger in patients with posttraumatic anosmia compared to patients with sinonasal disease. This may have implications for the medicolegal investigation of anosmic patients where trigeminal stimuli are frequently used to assess the patient’s response bias.

Assessment of intranasal trigeminal function

Intranasal trigeminal function is more and more understood as an integral part of human chemosensory perception. Sensations like burning, stinging, warmth, coolness, or itching are produced by almost all odorants so that they can be perceived by anosmics. Electrophysiological responses to trigeminal stimuli allow the specific assessment of trigeminally mediated information at different levels of processing including the periphery or the cortex. Information regarding the localization of these processes can be derived from magnetoencephalographic recordings or functional imaging data. When using these techniques in combination with psychophysical measures, it seems to be possible to specifically describe how and where the processing of irritation takes place, how it may interact with olfactory mediated sensations, and how it is modulated, e.g. by environmental influences or analgesic drugs.