Topical high‐concentration menthol: Reproducibility of a human surrogate pain model

Abstract

For an observation period of 1 week, the signs of cold and mechanical hyperalgesia were reproducible with a highly significant correlation of about r = 0.8 and good agreement except for the area size of mechanical pin-prick hyperalgesia. These results demonstrate that the topical menthol pain model is suitable for pharmacological interventions repeated within an observation period of 1 week.

High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde

“…In the present study we sought to evaluate the analgesic, anti-hyperalgesic and antiinflammatory effect of L-menthol to CA-induced sensory and vasomotor symptomatology, and as such did not include a condition with L-menthol alone, which is well known to induce prolonged cold hyperalgesia, spontaneous pain and primary and secondary hyperalgesia. 3,8,34,43,50,62,63 Topical application of 10% CA provoked mild pain, primary and secondary mechanical hyperalgesia, heat and cold hyperalgesia and substantial primary and secondary neurogenic inflammation. Notably, 3 subjects were considerably below the averagely reported pain peak values and scored ≤ 1 (0.80 ± 0.05) on the VAS versus 3.87 ± 0.46, for the remaining 11 subjects.…”

Cold and L-menthol-induced sensitization in healthy volunteers—a cold hypersensitivity analogue to the heat/capsaicin model

“…22,48 TRPA1 is suspected to be involved in noxious cold transmission (,15˚C) and is expressed on C-and Ad-fibers. 44 It is generally agreed 8,23,31,47 that application of L-menthol increases the average temperature of the cold pain threshold (CPT), reduces mechanical pain threshold, and increases mechanical pain sensitivity. However, there is still a lower consensus on the development of secondary mechanical hyperalgesia, its stability and the duration of its existence.…”

Evaluation of the antihyperalgesic effect of tapentadol in two human evoked pain models – the TapCapMentho pilot trial

“…Additionally, from the statistical review of effects it can be concluded from the distributions of values at premodel baseline and pre-tapentadol baseline that, in this study, a high variability in QST values could have influenced the outcome measures. For example, this might be explained by the fact that subjects were tested in the ratio 4 subjects: 2 investigators in one room and not in the ratio 1:1 previously described in evoked pain model studies [14,15] . This leads to the question of sample size and assay sensitivity that might have been too low in this complex study although common methods and sample sizes were used.…”

“…The topical menthol model demonstrated robust induction of cold and mechanical hyperalgesia with a high grade of reproducibility [14,15] . Similar data were shown for the capsaicin injection and heat-capsaicin model only, not for the topical application model used in this study.…”

“…Previous trials in healthy human subjects demonstrated that the topical application of menthol at a high concentration [40%] is suitable as an experimental model of cold and mechanical (pinprick) hyperalgesia [14,15] . Furthermore, trials in volunteers showed that the topical application of capsaicin is suitable as an experimental model of heat and mechanical (pinprick) hyperalgesia (for review see [4] ).…”