Oral thermosensing by murine trigeminal neurons:modulation by capsaicin, menthol, and mustard oil

Abstract

When consumed with foods, mint, mustard and chili peppers generate pronounced oral thermosensations. Here we recorded responses in mouse trigeminal ganglion neurons to investigate interactions between thermal sensing and the active ingredients of these plants -- menthol, allyl isothiocyanate (AITC), and capsaicin, respectively -- at concentrations found in foods and commercial hygiene products. We carried out in vivo confocal calcium imaging of trigeminal ganglia in which neurons express GCaMP3 or GCAMP6s and recorded their responses to oral stimulation with thermal and the above chemesthetic stimuli. In the V3 (oral sensory) region of the ganglion, thermoreceptive neurons accounted for [~]10% of imaged neurons. We categorized them into 3 distinct classes: cool-responsive and warm-responsive thermosensors, and nociceptors (responsive only to temperatures [≥]43-45{degrees}). Menthol, AITC, and capsaicin also elicited robust calcium responses that differed markedly in their latencies and durations. Most of the neurons that responded to these chemesthetic stimuli were also thermosensitive. Capsaicin and AITC increased the numbers of warm-responding neurons and shifted the nociceptor threshold to lower temperatures. Menthol attenuated the responses in all classes of thermoreceptors. Our data show that while individual neurons may respond to a narrow temperature range (or even bimodally), taken collectively, the population is able to report on graded changes of temperature. Our findings also substantiate an explanation for the thermal sensations experienced when one consumes pungent spices or mint.\n\nKey points summaryO_LIOrosensory thermal trigeminal afferent neurons respond to cool, warm, and nociceptive hot temperatures with the majority activated in the cool range.\nC_LIO_LIMany of these thermosensitive trigeminal orosensory afferent neurons also respond to capsaicin, menthol and/or mustard oil (allyl isothiocyanate, AITC) at concentrations found in foods and spices.\nC_LIO_LIThere is significant but incomplete overlap between afferent trigeminal neurons that respond to heat and to the above chemesthetic compounds.\nC_LIO_LICapsaicin sensitizes warm trigeminal thermoreceptors and orosensory nociceptors; menthol attenuates cool thermoresponses.\nC_LI