Sensory Topography of Oral Structures

Key Points

Question  What is the tactile sensory threshold topography of oral and oropharyngeal subsites?

Findings  In a cohort of 37 healthy adults (12 men, 25 women), the lower lip, anterior tongue, and buccal mucosa were more sensitive than the soft palate, posterior tongue, and posterior pharyngeal wall.

Meaning  Topography of normal oral cavity and oropharyngeal tactile sensation is organized in accordance to decreasing sensitivity along the anteroposterior trajectory.

Importance  Sensory function in the oral cavity and oropharynx is integral to effective deglutition and speech production. The main hurdle to evaluation of tactile consequences of upper aerodigestive tract diseases and treatments is access to a reliable clinical tool. We propose a rapid and reliable procedure to determine tactile thresholds using buckling monofilaments to advance care.

Objective  To develop novel sensory testing monofilaments and map tactile thresholds of oral cavity and oropharyngeal structures.

Design, Setting, and Participants  A prospective cross-sectional study of 37 healthy adults (12 men, 25 women), specifically without a medical history of head and neck surgery, radiation, or chemotherapy, was carried out in an academic tertiary medical center to capture normative data on tactile sensory function in oral structures.

Interventions  Cheung-Bearelly monofilaments were constructed by securing nylon monofilament sutures (2-0 through 9-0) in the lumen of 5-French ureteral catheters, exposing 20 mm for tapping action.

Main Outcomes and Measures  Buckling force consistency was evaluated for 3 lots of each suture size. Sensory thresholds of 4 oral cavity and 2 oropharyngeal subsites in healthy participants (n = 37) were determined by classical signal detection methodology (d-prime ≥1). In 21 participants, test-retest reliability of sensory thresholds was evaluated. Separately in 16 participants, sensory thresholds determined by a modified staircase method were cross-validated with those obtained by classical signal detection.

Results  Buckling forces of successive suture sizes were distinct (P < .001), consistent (Cronbach α, 0.99), and logarithmically related (r = 0.99, P < .001). Test-retest reliability of sensory threshold determination was high (Cronbach α, >0.7). The lower lip, anterior tongue, and buccal mucosa were more sensitive than the soft palate, posterior tongue, and posterior pharyngeal wall (P < .001). Threshold determination by classical signal detection and modified staircase methods were highly correlated (r = 0.93, P < .001). Growth of perceptual intensity was logarithmically proportional to stimulus strength (P < .01).

Conclusions and Relevance  Topography of normal oral cavity and oropharyngeal tactile sensation is organized in accordance to decreasing sensitivity along the anteroposterior trajectory and growth of perceptual intensity at all subsites is log-linear. Cheung-Bearelly monofilaments are accessible, disposable, and consistent esthesiometers. This novel clinical tool is deployable for quantitative sensory function assessment of oral cavity and oropharyngeal structures.

Sensation in the oral cavity and oropharynx is mediated by a rich assortment of receptors that respond preferentially to different aspects of sensory function—touch, pressure, vibration, position, pain, temperature, and taste.^1,2 Among them, tactile sensory feedback plays a critical role in safe and effective deglutition. Exquisite sensory function in the oral cavity is required for identification of food objects, action selection in mastication, and decision-making to trigger a swallow sequence. Beyond deglutition, tactile integrity allows for precise apposition of the lips, tongue movements, and palatal excursions to produce nuanced vocal expressions. The complex orchestration of oral cavity sensorimotor function can, however, become impaired by primary diseases or secondary treatment effects. An example is oral cavity sensory degradation following chemotherapeutic, radiotherapeutic, or surgical treatment for head and neck malignant conditions.^3-6 Oral cavity sensory dysfunction may emerge in the absence of external insults, notably in association with snoring and obstructive sleep apnea disorders.^7-10 It follows that an accessible and reliable clinical tool to quantify oral cavity and oropharyngeal tactile sensory function could be broadly useful to advance care for patients with ailments that impact the upper aerodigestive tract.

For the most part successful clinical adoption of cutaneous sensory testing has been limited to screening for diabetic foot neuropathy. Variations of testing monofilaments that deliver similar buckling forces have been marketed to identify foot plantar surfaces at risk for skin breakdown. The scientific basis for this practice originated from the use of monofilaments to deliver a gradation of reliable forces to cutaneous surfaces by von Frey in 1899, using horse hairs of varying diameters.¹¹ Semmes-Weinstein monofilaments were then developed, which replaced horse hairs with a set of calibrated nylon monofilaments. Each monofilament has a known buckling force,¹² a constant force exerted by the free tip on a contact surface over a wide range of curvilinear displacements. If an individual cannot detect a buckling monofilament applied to a particular skin area, then the “yes” or “no” detection response is recorded as a “no.” Successively larger forces are applied until the response is “yes,” marking the sensory detection threshold. The testing procedure may be performed in the opposite direction, from larger to smaller forces, where the last detectable monofilament is recorded as the threshold value. Screening for diabetic foot neuropathy is based on a cutoff threshold that delimits unacceptable risk of adverse outcomes. In this context, adoption of quantitative oral cavity tactile testing to evaluate sensory dysfunction in swallowing, voicing, and breathing disorders would sharpen diagnostic evaluation and inform treatment innovation. To our knowledge, there are only a few somatosensory studies^13,14 in the oral cavity, and none have measured tactile thresholds of subsites across the entire anteroposterior axis in participants in a rigorous manner.

The principal barriers to conducting more comprehensive sensory mapping studies of oral structures are 2-fold. The first is that Semmes-Weinstein monofilaments are mounted on bulky handles at 90 degrees, creating challenges for maneuverability in the mouth. The second is a lack of accessible, disposable monofilaments that can be easily manufactured by health care providers on demand. To overcome those hurdles, we crafted a novel sensory testing instrument that is easy to assemble using widely accessible components, performs in a consistent and reliable manner, and offers improved maneuverability. This study validates the novel monofilaments and testing methods, and documents tactile sensory thresholds and growth of perceptual intensity profiles in 4 oral cavity and 2 oropharyngeal subsites in a cohort of healthy adults.

Cheung-Bearelly monofilaments with 20 mm exposed for tapping action were constructed from commonly available materials in medical practice: 5-French open lumen catheters, off-the-shelf monofilament nylon sutures, and silicone-based adhesives. There were 3 steps to the manufacturing process. Step 1: monofilament handles were constructed by cutting 5F ureteral catheters (Cook Medical) into 12-cm segments to comfortably reach oral subsites for tapping action. Step 2: nylon monofilament sutures (2-0 through 9-0; Ethicon) were secured to the catheter tip by either of 2 methods (Figure 1, A). Method 1: affix 3 mm of the nylon suture into the proximal catheter lumen using a silicone-based adhesive (Nusil Technology). Method 2: make 180-degree opposing perforations 3 mm from the proximal catheter lumen using a 25-gauge needle and bisect the perforations by cutting a single 4-mm longitudinal slit, followed by passage of nylon suture material through those 2 perforations to partially circumnavigate the outer catheter perimeter across from the slit, and affix the nylon suture to the proximal catheter lumen by tying a knot inside the lumen (made possible by opening slit). Step 3: Cheung-Bearelly monofilaments were readied for use by trimming excess suture material to expose 20 mm in the silicone-based adhesive method and 17 mm (plus 3 mm inside catheter lumen yields 20 mm) in the surgical knot method. The latter did not require an adhesive and eliminated any theoretic possibility of monofilament dislodgement from the handle. Throughout this study, we refer to smaller sutures as those with smaller caliber diameters, such as 8-0 and 9-0. Conversely, we refer to larger sutures as those with larger caliber diameters, such as 2-0 and 3-0.

A digital laboratory analytical scale (Shimadzu Electronic Balances, accuracy rating 0.001 g) was used to determine buckling forces of Cheung-Bearelly monofilaments. Testing was limited to nylon suture sizes from 2-0 to 7-0, as 8-0 and 9-0 sizes were beyond the instrument’s range. Each monofilament was applied perpendicular to the scale plate until it buckled by approximately 30% and a stable reading was obtained. This procedure was repeated 20 times per suture size. Monofilament manufacturing consistency was evaluated by testing 3 different lots of each suture size. Because each monofilament is made from the same material and cylindrical in shape, buckling force delivered at the tip is expected to vary with cross-sectional area (buckling force = constant × diameter).² Therefore, logarithmic transformation of buckling force would linearize the relationship to suture size. The buckling forces for 8-0 and 9-0 suture sizes were estimated by a log-linear regression model.

We recruited healthy adult male and female participants. Inclusion criteria required participants to communicate in English without difficulty. Exclusion criteria precluded those with history of head and neck surgery, head and neck radiation therapy or chemotherapy, or trismus from participation. The study was approved by the Committee on Human Research at the University of California, San Francisco. All participants were informed of study objectives, acknowledged study tasks, and provided written informed consent. They were compensated with $75 per study session.

At total of 12 men (mean [SD] age, 39 [18] years) and 25 women (mean [SD] age, 42 [14] years) participated in this study. Sensory thresholds of the lower lip, anterior oral tongue, buccal mucosa, soft palate, posterior oral tongue, and posterior pharyngeal wall were determined by classical signal detection¹⁵ methodology (d-prime ≥1). Twenty-one participants underwent 2 testing sessions, at least 3 days apart, for sensory threshold reliability evaluation. Separately in 16 participants, sensory thresholds determined by a modified staircase¹⁶ method were compared with those obtained by classical signal detection for cross-validation assessment. A global tactile threshold topographic map of oral cavity and oropharyngeal structures (Figure 1B) was reconstructed using pooled data from all 37 participants. Average distances relative to the lower lip along the anteroposterior axis for the 4 oral cavity and 2 oropharyngeal subsites were computed from a review of 10 adult magnetic resonance imaging scans accessed from the film library collection. Relative distances among subsites permitted construction of a tactile threshold vs subsite position plot for each participant to extract slope values along the anteroposterior axis for the entire cohort.

Prior to a testing session, the anterior tongue was briefly screened with several of the smaller sutures to provide instruction to the participant for a 2-alternative forced choice (yes/no) response and to establish a rough estimate of the tactile threshold. The participant was informed that testing would include no stimulus conditions (catch trials). Monofilaments typically buckled by approximately 30% of length during tapping. During a particular test sequence, the participant kept eyes closed and was alerted to pay attention by a short tone pip. Tactile sensory mapping of oral structures was performed in the midline, save for buccal mucosa, which was consistently performed on the left. Testing order of the 6 subsites for each participant was randomized. At each subsite, a specific randomly generated order of 18 active and 6 catch trials was used for testing, and this stimulus sequence was repeated for all participants. The threshold suture size was defined as the smallest monofilament caliber that met the criterion of discriminability index or d-prime of 1.0 or greater. Discriminability index is a statistical measure of observer ability to discriminate between signal and nonsignal. Statistics of hit (“yes” to signal divided by “yes” and “no” to signal) and false alarm (“yes” to nonsignal divided by “yes” and “no” to nonsignal) responses were transformed into standardized z scores, where d-prime was the separation between the 2 distributions in standard deviation units. For example, if participants correctly responded to a high percentage of signals but also incorrectly respond to a high percentage of nonsignals, then discriminability between signal and nonsignal was poor (low d-prime value). Data were collected by starting with the largest caliber monofilament, followed by successively smaller caliber monofilaments until the terminal 9-0 monofilament was reached. A retest session in 21 participants to measure a second set of sensory thresholds was performed at least 3 days apart from the initial test session. The same procedures were followed.

We modified a staircase method to develop a rapid procedure that would be clinically deployable. While rigorous, the classical signal detection method was time consuming and impractical for routine clinical use. The staircase method started with the largest monofilament (2-0 suture) and successively progressed to smaller monofilaments until an initial estimate of threshold was obtained. The neighborhood of the initial estimate was then further interrogated. The estimated suture size, 1 suture size smaller, and 1 suture size larger were selected to perform additional trials. Four separate taps were presented for each suture size, starting from the largest and ending with the smallest. The smallest caliber suture size with 3 out 4 affirmative responses was selected as the tactile threshold.

Fechner’s Law¹⁷ states that the growth of sensory percept intensity is logarithmically proportional to the physical intensity of the stimulus. This assertion was evaluated for the following 4 oral subsites: anterior tongue, buccal mucosa, soft palate, and posterior tongue. Perceptual intensity was referenced to the lower lip. Growth of perceptual intensity for each participant was determined by using the lower lip threshold (Thr) monofilament plus 4 successively larger monofilaments (Thr-1, Thr-2, Thr-3, and Thr-4) to present taps for grading on ordinal scale for intensity (1 = slight, 2 = mild, 3 = medium, 4 = medium-high, 5 = high). Testing order of these 4 oral subsites was randomized.

Monofilament buckling force consistency and sensory threshold test-retest reliability were measured by Cronbach α values. Signal detection theory procedures were used to determine sensory thresholds. Tactile sensory threshold was defined as the smallest caliber testing monofilament that generated a d-prime of 1.0 or greater or satisfied the modified staircase criterion. Analysis of variance was used to assess sensory threshold inhomogeneity among subsites, followed by post hoc methodology to identify specific groups of subsites that differed. Standard log-linear least squares regression techniques with 95% CIs were applied to buckling force, perceptual intensity, and topographic threshold gradient analyses. Paired t tests with Bonferroni correction were used to compare growth of perceptual intensity at 4 subsites.

The mean buckling force for each monofilament size was distinct (Table) from all other monofilament sizes (P < .001). The mean buckling force for a specific monofilament was consistent across 3 different lots (95% CIs overlap), save lot A of the 4-0 monofilament (Table). The source of this singular nonoverlap across lots is unclear, but the buckling force of lot A 4-0 monofilament was significantly different from neighboring 3-0 and 5-0 monofilaments from all lots. There was no statistical difference in buckling forces between silicone-based adhesive and knot tying techniques to secure a particular monofilament to 5-French ureteral catheters. The relationship between raw buckling force and monofilament size was substantially nonlinear (Figure 2, dotted line). Through logarithmic transformation of buckling force, its relationship to monofilament size may be linearized by least squares regression (Figure 2, black line): log buckling force = −0.4765 × monofilament size number +1.6765 (r = 0.99, P < .001). From this model, extrapolation to 8-0 and 9-0 monofilament suture sizes permit data imputation to complete (Table). The mean (SD) change in buckling force of successive monofilaments was 4.7 (0.7) dB. The dynamic range of Cheung-Bearelly filaments used for this experiment spanned from 2-0 to 9-0 monofilament sizes or 33 dB.

The lowest tactile threshold was found for the anterior tongue and highest for the posterior oropharyngeal wall. That is, the anterior tongue was much more sensitive to tactile stimulation. Analysis of variance revealed inhomogeneity among the 6 subsites (P < .001). Frequency plots showed essentially Gaussian distributions of tactile sensory thresholds for all 6 subsites (Figure 3A, dot marks indicate mean). The mean threshold accounted for approximately 50% of occurrences. Post hoc analysis showed the lower lip, anterior tongue, and buccal mucosa were more sensitive than the soft palate, posterior tongue, and posterior pharyngeal wall (P < .001). In the subset of 21 participants (6 males, 15 females; median age, 41 years; range, 22-78 years) who underwent a second testing session, test-retest reliability was high at each subsite (Cronbach α >0.7).

The anterior tongue, buccal mucosa, soft palate, and posterior tongue demonstrated linear rise in perceptual intensity relative to logarithmically transformed buckling force (Figure 3B), but showed variations in the slope steepness or growth of perceptual intensity. Subsite perceptual intensity growth curves were computed by fitting a least squares linear regression line to perceptual intensity rating vs monofilament suture size (stimulus intensity). All 4 oral cavity subsites confirmed linear growth of perceptual intensity that were significant (P < .01). Paired t tests with Bonferroni correction for multiple comparisons revealed the anterior tongue had a more rapid growth profile in perceptual intensity compared with the palate (0.73 vs 0.43, P < .01) (Figure 3B). The remaining comparisons did not reveal significant differences.

An overall least squares linear regression model was applied to threshold vs subsite position data for all 37 participants. A minimum of 3 data points was required for individual least squares linear fits. The topographic organization of normal oral tactile sensation revealed anteriorly positioned structures were more sensitive than those posteriorly positioned in a predictable and consistent manner (relative distance range: lower lip, 0 mm; posterior pharyngeal wall, 91 mm) (Figure 4). The global monotonic gradient of oral tactile sensitivity along the anteroposterior axis was significant (mean slope, −0.028; 95% CI, −0.033 to −0.023).

In 16 participants, 3 separate subsites (anterior tongue, buccal mucosa, and posterior tongue) were selected for threshold determination using both classical signal detection and a modified staircase method for rapid assessment. By combining data across all subsites for all participants, thresholds determined by the 2 methods were strongly correlated (r = 0.93, P < .001).

Cheung-Bearelly monofilaments have been specifically designed to evaluate intraoral tactile thresholds. While Semmes-Weinstein monofilaments have been the gold standard for sensory testing of the extremities, right angled handles are too bulky for use within the oral cavity and replenishment of the set after single use (salivary contamination, risk of transmittable diseases) in a patient seems uneconomical. We propose a novel esthesiometer where the smaller handle is collinear with the testing monofilament, allowing for much greater maneuverability within the narrow confines of the oral cavity. Cheung-Bearelly monofilaments are easy to assemble, crafted for environmental sustainability, consistent across suture lots, and distinct in delivery of calibrated buckling forces from 1 suture size to the next.

Highly reliable determination of tactile sensory thresholds in 6 oral subsites using Cheung-Bearelly monofilaments shows a systematic variation in sensitivity along the anteroposterior axis. The anterior tongue and lower lip are the most sensitive and the posterior oropharyngeal wall is the least sensitive. The biological basis of this gradient in oral sensory topography may be an activity dependent consequence imposed on the anterior tongue and lower lip, because those structures are more likely to explore the environment and trigger motoric action compared with the posterior oral tongue and oropharynx. Greater sensitivity and finer discrimination capabilities may confer advantages in food type identification, voiceless plosive production, nonverbal gesture communication, and sensorimotor coordination in deglutition. Plasticity experiments in humans^18-20 and animals^21-25 have demonstrated improvement in skin surface sensitivity and refinement in 2-point discrimination following skill acquisition through learning-based tasks. Cheung-Bearelly monofilaments enable measurement of oral structure sensory change caused by chemotherapy, radiation therapy, surgery and aging, and facilitate treatment deintensification tradeoff analyses that weight increment in disease control certitude vs increment in toxicity by providing a quantitative metric of functional outcome.²⁶

Confirmation of a logarithmic relationship between tactile perceptual intensity growth and stimulus intensity is potentially useful for monitoring systemic treatments that impact the oral cavity. Certain drugs, such as macrolides and antifungals, can have adverse effects that manifest as oral cavity dysesthesias,²⁷ suggesting potential usefulness to measure growth of perceptual intensity. Growth of perceptual intensity profile is an additional evaluative dimension to complement tactile thresholds that constitute an oral sensory map or “tactorogram” to evaluate individuals. Other metrics of sensory function include 2-point discrimination and flutter detection.

There are certain limitations to this study. Off-the-shelf use of Ethicon nylon sutures limits stimulus granularity. This is most germane in the modified staircase neighborhood interrogation procedure, where finer resolution could have increased measurement precision. It may be possible to partner with Ethicon to manufacture intermediate suture sizes. Alternatively, increasing monofilament length from 20 mm to 25 mm could have provided intermediate forces ([2/2.5]² = 0.64), because buckling force is inversely related to the square of monofilament length. The buckling forces of 8-0 and 9-0 sutures are estimated from a regression model based on measurements from 2-0 through 7-0 Ethicon nylon sutures, but a more advanced analytical scale can be acquired to make those measurements directly.

There are immediate implications from this study. Because this investigation documents reference values of oral sensory thresholds and perceptual intensity growth profiles for a healthy control cohort, Cheung-Bearelly monofilaments or equivalent tools may be deployed in clinical practice. Among the many applications, we can start to address how oral sensory function differs in aging and snoring, recovers after treatment for upper aerodigestive tract cancer, evolves in transfer of reinnervated tissue, and interacts with motoric action in swallowing, voicing, and breathing.

Cheung-Bearelly monofilaments are accessible, disposable, and consistent esthesiometers for reliable determination of sensory thresholds of oral structures. The global topography of normal oral cavity and oropharyngeal tactile sensation is organized in accordance to decreasing sensitivity along the anteroposterior trajectory. By using a modified staircase test method to determine tactile thresholds rapidly, Cheung-Bearelly monofilaments may be deployed to evaluate oral sensory function in more detail. This clinical tool may be useful to monitor sensory function recovery after chemotherapy or radiation treatment of oral cavity cancers and reconstruction of oral cavity defects, and other conditions that impact oral sensorimotor function.

Corresponding Author: Steven W. Cheung, MD, Departments of Otology, Neurotology, and Skull Base Surgery, University of California, San Francisco, 2233 Post St, Third Floor, San Francisco, CA 94115 (Steven.Cheung@ucsf.edu).

Published Online: September 29, 2016. doi:10.1001/jamaoto.2016.2772

Author Contributions: Drs Bearelly and Cheung had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: All authors.

Obtaining funding: Cheung.

Study supervision: Cheung.

Conflict of Interest Disclosures: None reported.

Funding/Support: The study was supported by the UCSF Department of Otolaryngology–Head and Neck Surgery Coleman Memorial Fund and Hearing Research, Inc.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.