Development of a topical menthol stimulus to evaluate cold hyperalgesia

Abstract

PurposeCold hyperalgesia is an indicator of widespread pain sensitivity and is associated with poor clinical outcomes. Menthol activates TRPM8, a cold-sensing receptor channel. This research evaluated topical menthol as a potential stimulus to be used in the clinical evaluation of cold hyperalgesia. MethodsParticipants were 59 pain free volunteers (17 male: 42 female). A blinded, repeated measures design was used. Participants received applications of menthol at different concentrations in a liquid (study 1) or gel (study 2) formulation with a 24-h interval between each application. Each menthol concentration was applied for 15 min and participants were asked to rate the sensation produced using a series of visual analogue scales and by selecting words from a descriptor list derived from the McGill pain questionnaire (MPQ). The menthol was applied to a site on the volar forearm. Participants also had their cold pain thresholds (CPT) evaluated at the same site using a contact thermode. ResultsThere were significant concentration-dependent effects for intensity of cold, unpleasantness and pain VAS: cold F(2,62) = 8.67, p < 0.001; unpleasantness χ2(2) = 14.14, p < 0.001; χ2(2) = 11.74, p = 0.003, with moderate effect sizes for unpleasantness and pain. There were also significant concentration dependent effects for descriptor indices, pain rating index (PRI) F(2,62) = 26.33, p < 0.001; number of words chosen (NWC) F(2,62) = 19.62, p < 0.001, with large effect sizes for 10–20% and 10–30% comparisons. Significant correlations were seen between measures of unpleasantness, pain, PRI, NWC and CPT dependent on menthol concentration. ConclusionTopical menthol has potential as a stimulus to evaluate cold hyperalgesia.