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Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM 8 and TRPA 1 using topical L ‐menthol and trans ‐cinnamaldehyde in healthy volunteers
Author(s) -
Olsen R.V.,
Andersen H.H.,
Møller H.G.,
Eskelund P.W.,
ArendtNielsen L.
Publication year - 2014
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2014.494.x
Subject(s) - menthol , trpm8 , nociceptor , allodynia , vasomotor , medicine , hyperalgesia , capsaicin , transient receptor potential channel , chemistry , axon reflex , pharmacology , anesthesia , reflex , receptor , nociception , trpv1 , organic chemistry
Abstract Background Activation of TRPM 8 and TRPA 1 receptors generates cold and cold pain sensations, respectively, and is presumably important in clinical pain manifestations, such as cold hyperalgesia. This study investigated the interaction between TRPM 8 and TRPA 1 receptors through stimulation of glabrous human skin (volar forearm) by topical administration of 40% L ‐menthol and 10% trans ‐cinnamaldehyde ( CA ), individually and in combination. Methods Sensory manifestations were assessed in 10 healthy volunteers via a platform of 11 quantitative sensory (thermal and mechanical stimuli) and vasomotor tests (skin temperature, perfusion and axon‐reflex‐flare) in a double‐blinded randomized crossover design. Results Cold pain threshold was increased ( p < 0.01, cold allodynia) by L ‐menthol alone and L ‐menthol + CA in combination but unaffected by CA . Mechanical pain threshold was significantly decreased (mechanical hyperalgesia) by all three substances ( p < 0.01), with a significant intergroup difference found between CA alone and the less decreased L ‐menthol + CA ( p < 0.05). Application of CA alone and L ‐menthol + CA in combination showed an increase in skin temperature and perfusion significantly larger than that induced by L ‐menthol alone ( p < 0.05). An axon‐reflex‐flare was present after CA administration, but was significantly reduced upon addition of L ‐menthol ( p < 0.01). Conclusion This study elucidates the potential of L ‐menthol as a counter‐irritant to secondary neurogenic inflammation and provides evidence of an intricate interplay between cold receptors TRPA 1 and TRPM 8, warranting further investigation of the neural coding of cold pain perception.