Responses to the activation of different intranasal trigeminal receptors: Evidence from behavioral, peripheral and central levels

Behav Brain Res. 2025 Mar 5:480:115371. doi: 10.1016/j.bbr.2024.115371. Epub 2024 Dec 3.

Abstract

Aim: There are various receptors that mediate intranasal trigeminal sensations. However, few studies compare the response patterns across different receptor activations.

Methods: We recorded negative mucosal potentials (NMPs) in 24 healthy participants and event-related potentials (ERPs) in 17 participants during exposure to five odors that trigger trigeminal sensations and one olfactory stimulus. Additionally, 10 participants completed a continuous odor intensity rating task.

Results: We observed a significant effect of odor type on NMP amplitudes (F=13.51-21.88, p's < 0.01), with cyclohexanone (TRPV1) and CO2 (TRPV1 +A1) inducing greater N1 and/or P1N1 amplitudes than other stimuli (t = 3.28-7.54, p's < 0.05). Similar differences were seen in ERP amplitudes (F=3.69-12.25, p's < 0.05), with cyclohexanone showing greater P2 and/or N1P2 amplitudes than PEA (odorant), carvacrol (TRPV3 +A1), and perillaldehyde (TRPA1) (t = 3.13-4.10, p's < 0.05). CO2 also produced greater amplitudes than carvacrol (t = 3.53-4.42, p's < 0.05). In the odor intensity rating task, cyclohexanone, CO2, and isopulegol (TRPM8 +TRPA1) had higher peak ratings, steeper slopes, and/or shorter latencies (F=6.15-13.86, p's < 0.01; t = 3.14-7.76, p's < 0.05).

Conclusions: Activation of different intranasal trigeminal receptors yields varied responses. Notably, stimuli involving TRPV1 activation, linked to irritation or pain, elicited stronger behavioral and neural activity compared to stimuli involving other receptors, even when controlling for rated stimulus intensity. This emphasizes TRPV1's significance in survival adaptation. Future studies should test different sets of stimulants to verify the robustness of these findings.

Keywords: Event-related potential (ERP); Intranasal trigeminal perception; Negative mucosal potential (NMP); Odor intensity; Somatic sensation; Transient receptor potential (TRP).

MeSH terms

  • Adult
  • Electroencephalography
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology
  • Female
  • Humans
  • Male
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / physiology
  • Odorants*
  • Olfactory Perception / physiology
  • Smell / physiology
  • TRPV Cation Channels / metabolism
  • Trigeminal Nerve / drug effects
  • Trigeminal Nerve / physiology
  • Young Adult

Substances

  • TRPV Cation Channels