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.

Abstract

<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.