Topical high-concentration (40%) menthol-somatosensory profile of a human surrogate pain model

Cold hyperalgesia is 1 of the characteristic signs in neuropathic pain. Topical application of menthol has been proposed as model to study cold hyperalgesia. The aim of this psychophysical study was to characterize the human surrogate of neuropathic pain of topical menthol application by using a standardized and validated protocol of quantitative sensory testing (QST). Additionally, we assessed the course of the signs elicited by menthol application over time. High-concentration 40% L-menthol was applied topically on hairy skin in 12 healthy subjects. Standardized psychophysical tests (QST) assessing 13 parameters including thermal and mechanical detection and pain thresholds were obtained before and every 45 minutes after menthol removal up to 4 hours after menthol application. Menthol decreased the cold pain threshold, mechanical pain threshold, and increased the mechanical pain sensitivity in all subjects displaying cold and mechanical pinprick hyperalgesia. In all subjects, an area of secondary pinprick hyperalgesia could be determined. Within the observation time, the decreased cold pain threshold increased continuously, whereas the signs of primary and secondary pinprick hyperalgesia remained stable. The data suggest that topical 40% menthol application is a useful model for studies of cold hyperalgesia and pinprick hyperalgesia in humans.

This study establishes the topical application of high-concentration 40% menthol as a useful stable model for studies of cold hyperalgesia and pinprick hyperalgesia in humans. The provided long-term data are important for psychophysical and pharmacological research in humans and provide us with insights on experimental cold and mechanical hyperalgesia.