# Single Inhalation of Peppermint Essential Oil Alleviates Acute Restraint Stress‐Exacerbated Itch in Oxazolone‐Induced Mild Dermatitis: Correlations With Brain Neuronal Activity in Female BALB/c Mouse

## TL;DR

Inhaling peppermint essential oil reduces stress-related itching in mice with mild skin inflammation, possibly by affecting brain activity.

## Contribution

Shows that PEO inhalation alleviates stress-exacerbated pruritus in a mouse model of dermatitis.

## Key findings

- PEO inhalation reduced scratching behavior in mice with OXA-induced dermatitis and stress.
- c-Fos-positive cells in itch-related brain regions correlated with pruritic responses.
- Stress alone increased scratching behavior regardless of dermatitis presence.

## Abstract

Introduction: Peppermint essential oil (PEO) and its main component, menthol, are used in Western and Eastern traditional medicine for their anti‐spasmodic, anti‐septic, or anti‐pruritic properties. Although topical application of PEO exhibits anti‐pruritic efficacy, the effects of PEO inhalation on itch sensation and pruritic behavior remain unclear. We aimed to determine whether PEO inhalation alleviates pruritus and itch‐responsive neural activity in the brains of mice with hapten‐induced dermatitis under acute stress conditions.

Methods: Forty‐one female BALB/c mice were randomly assigned to six experimental groups. Twenty‐nine mice were subjected to oxazolone (OXA)‐induced dermatitis through an initial sensitization followed by three rounds of topical application of OXA every other day. During the final OXA application, twenty‐two mice were exposed to restraint stress for 2 h. Sixteen mice were subjected to the inhalation of 2.5% PEO. The total duration of scratching bouts and the number of c‐Fos‐positive cells in the parabrachial nucleus, central amygdala, periaqueductal gray, and ventral tegmental area were quantified.

Results: PEO inhalation reduced the duration of scratching behavior induced by the combination of repeated OXA application and acute restraint stress. The c‐Fos‐positive cell number in the tested brain regions, except the ventral tegmental area, was positively correlated with the pruritic response. PEO inhalation alleviates OXA‐ or stress‐induced pruritus by modulating neuronal activity in itch‐related brain regions.

Conclusion: Acute restraint stress exacerbates itch, and PEO inhalation alleviates the stress‐associated aggravation of pruritus caused by OXA‐induced dermatitis, which is associated with the modulation of neuronal activity in itch‐related brain regions.

Acute restraint stress increased the total duration of scratching behavior in mice regardless of whether dermatitis is present. The number of c‐Fos‐positive cells correlated with pruritic responses. Inhalation of peppermint essential oil alleviated OXA‐induced pruritus under stress conditions and increased the number of c‐Fos‐positive cells in the itch‐responsive brain region.