Electronic Cigarette Liquid Constituents Induce Nasal and Tracheal Sensory Irritation in Mice in Regionally Dependent Fashion.

Introduction:
This text provides an in-depth analysis of the effects of e-cigarette liquids on the respiratory system, specifically focusing on the sensory irritation caused by e-cigarette constituents. The study uses ERP (event-related potential) recordings from nasal and tracheal mucosa to assess the sensory irritation caused by e-cigarette constituents and uses an antibody against phospho-S6 ribosomal protein (pS6) to immunolabel activated neurons in trigeminal ganglion (TG) and brainstem nuclei receiving airway nociceptive sensory input.

Key Points:

* The study found that individual constituents and mixtures of e-liquids, capsaicin, and citric and acetic acids evoked significantly larger ERP in the nose than in the trachea, with the exception of menthol.
* ERP responses to freebase nicotine were significantly larger than protonated nicotine, while four nicotine salts (benzoate, lactate, levulinate, and salicylate) induced similar responses.
* Compared with air-exposed mice, e-liquid aerosol-exposed mice showed a significant increase in numbers of activated trigeminal nociceptive neurons and brainstem neurons in the spinal trigeminal nucleus, paratrigeminal nucleus, and nucleus tractus solitaries.
* The study found no significant sex differences in responses to each of the stimuli tested, and pooled the data from males and females for all experiments.
* The ERP responses differed between protonated versus freebase nicotine at different ph levels, with the ERP response amplitude elicited by nicotine increasing significantly at higher phs tested.
* Nicotine benzoate elicited concentration-dependent nasal ERP responses, while Na benzoate and benzoic acid at 100 to 500 µM evoked only small responses.
* E-liquid aerosol exposure significantly increased the number of TG neurons expressing both substance P and pS6, indicating that e-liquid constituents activated some trigeminal nociceptive neurons.
* aerosol exposure significantly increased the numbers of pS6-labeled neurons in many regions of the nuclei of the Sp5C, Pa5, and NTS, providing evidence for the e-liquid aerosol-exposure induced sensory irritation or nociception in both the upper and the lower airways.

Main Message:
The study highlights the sensory irritation caused by e-cigarette constituents, specifically the effects of nicotine and flavorings on the respiratory system. The study's findings suggest that the higher sensitivity of the nasal nociceptive chemosensory system to nicotine and flavorings may indicate a health risk for e-liquid aerosol-induced upper airway illnesses via neurogenic alteration. The study's results underscore the need for further investigation into the potential health risks associated with e-cigarette use.

Ni F, Ogura T, Lin W. Electronic Cigarette Liquid Constituents Induce Nasal and Tracheal Sensory Irritation in Mice in Regionally Dependent Fashion. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco. 2020;22:S35-S44. doi:10.1093/ntr/ntaa174