Intra-oral digital pain and sensory mapping for complex sensory research

Digital body mapping is widely recognised as a standardized method to quantify pain in musculoskeletal research. However, its scientific utility extends far beyond backs, knees, and large body areas. One of the earliest demonstrations of this broader potential came from a controlled experimental platform assessing intra-oral irritation and sensory modulation during nicotine and menthol exposure. This study, conducted at Aalborg University, highlights how precise digital mapping enables detailed quantification of spatiotemporal sensory responses in small, anatomically complex regions.

Why Map Sensation Inside the Mouth?

Nicotine replacement therapies, such as nicotine gum, frequently produce burning, tingling, and irritation—affecting compliance and user experience. Understanding these effects requires not just intensity ratings but spatially resolved data: where does irritation occur, how does it spread, and how do additives like menthol modulate these patterns?

Traditional questionnaires cannot capture these spatial dynamics. Thus, the research team implemented a custom intra-oral digital body mapping schema, allowing participants to continuously map irritation regions on the tongue, palate, and throat. Pixel-based feature extraction made these drawings quantifiable, supporting direct comparisons across conditions, time points, and participant subgroups.

Notably, this approach demonstrates that digital body mapping is not anatomically constrained—the method adapts to any region where spatial representation adds scientific value.

Study Design: Two Blinded, Controlled, Cross-Over Experiments

Two investigations were performed using healthy, non-smoking volunteers:

Study I – Nicotine Dose-Response (N = 20)

Participants chewed gums containing 0 mg, 2 mg, or 4 mg nicotine.

Study II – Nicotine–Menthol Interaction (N = 22)

Participants chewed gums containing 30 mg menthol, 4 mg nicotine, or a combined menthol + nicotine formulation.

Sensory testing platform integrating intra-oral digital body mapping to quantify and map the area and spatial location of pain and irritation as experienced in the mouth and throat regions alongside a typical quantitative sensory testing (QST) battery.

Both studies used:

• Double-blinding

• Placebo-controlled, randomized, cross-over designs

• Standardized chewing regime (40 chews/min, 10 min total)

  
  

• Multimodal measurement test platform consisting of:

  • Heart rate and blood pressure

  • Quantitative Sensory Testing (CDT, WDT, CPT, HPT) on the tongue

  • Intra-oral blood flow and temperature via laser Doppler

  • Minute-by-minute pain and irritation intensity

  • Digital mapping of intra-oral and throat irritation area

  • McGill Pain Questionnaire descriptors

  • Sensory–taste profiling

    
    

The test platform integrated psychophysics, vasomotor physiology, and spatial mapping to create a rich multimodal dataset.

Key Findings Supported by Intra-oral Digital Pain Mapping

Transient reduction in pain intensity when menthol is combined with nicotine (left) and nicotine masked the cooling effects of menthol rather then menthol exerting a cooling sensation when combined with nicotine (right), Data source from Arendt-Nielsen T, Wang K, Nielsen BP, Arendt-Nielsen LA, Boudreau SA (2016) Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study" J. Nicotine Tob Research, 18(5):596-603. 

1. Nicotine produced dose-related irritation intensity but similar spatial patterns (Study I).

Both 2 mg and 4 mg doses produced rapid increases in irritation intensity during the first 2–3 minutes (P < .008). However, area of irritation during chewing did not differ between doses. Only after chewing did the 4 mg dose exhibit a continuing expansion of throat irritation, visualized clearly through digital mapping.

2. Menthol modulated intensity, not area, in early phases (Study II).

In the first 4 minutes, menthol reduced nicotine-induced irritation intensity (P < .017) but did not alter the spatial extent of irritation. This distinction between intensity and distribution underscores the importance of mapping over relying on scalar ratings alone.

3. Spatial profiles revealed individual phenotypes: “menthol responders.”

Approximately half of the participants reported irritation to menthol alone and marked these areas on the intra-oral schema. These menthol responders displayed:

• larger nicotine-induced throat irritation areas post-chewing (F = 11.377, P = .002),

• regardless of whether they received nicotine alone or the nicotine–menthol combination.

This phenotype could only be identified through spatially resolved data.

The discovery of phenotypes or individuals responding to menthol as an irritant showed greater areas of irritation (pixels) in the throat, which was evident 5-min post chewing (approx. 15 min from initial exposure) - Adopted and modified from: Arendt-Nielsen T, Wang K, Nielsen BP, Arendt-Nielsen LA, Boudreau SA (2016) Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study" J. Nicotine Tob Research, 18(5):596-603. 

4. Nicotine masked menthol’s cooling, sweetness, and freshness.

Taste-profiling revealed that nicotine attenuated menthol-associated cooling and freshness (P < .002), contrary to expectations that menthol would mask nicotine irritation. These findings align with TRPM8/TRPA1 receptor interactions and highlight cross-modal modulation between chemesthetic and gustatory pathways.

5. Vasomotor responses were similar across gums.

Laser Doppler measurements showed:

• subtle but consistent increases in superficial tongue blood flow and temperature during chewing (P < .017),

• with no differential effects between nicotine, menthol, or combination gums.

This suggests that irritation patterns captured via mapping arise from perceptual and neurophysiological mechanisms, not peripheral vascular changes.

Implications for Sensory Science and Digital Body Mapping

This study demonstrates that intra-oral digital (pain) body mapping:

• quantifies sensation in small, high-resolution anatomical regions,

• captures temporal dynamics of irritation and pain,

• identifies inter-individual sensory phenotypes,

• supports multimodal integration with QST, cardiovascular, and vasomotor data,

• and detects compound interaction effects that are invisible to single-modality methods.

  
  

Importantly, the spatial insights, such as persistent throat irritation after high-dose nicotine or enhanced responses among menthol responders, could only be detected through precise digital mapping. These findings informed product design considerations for nicotine gums, but more broadly, they illustrate the value of spatial sensory data in pharmacology, oral physiology, and consumer neuroscience.

Summary

Intra-oral digital body mapping is far more than a musculoskeletal tool. Intra-oral studies like this one reveal its power to characterize complex sensory experiences, differentiate individual response profiles, and quantify subtle interactions. As research moves toward more personalised and mechanistically grounded sensory assessment, digital body mapping offers a scalable, adaptable, and analytically rich method ready for applications across physiology, psychophysics, neuroscience, rehabilitation, and product R&D.

References

Arendt-Nielsen T, Wang K, Nielsen BP, Arendt-Nielsen LA, Boudreau SA (2016) Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study" J. Nicotine Tob Research, 18(5):596-603.