title: Topical application of L-menthol induces heat analgesia, mechanical allodynia, and a biphasic effect on cold sensitivity in rats.
abstract: Menthol is used in analgesic balms and also in foods and oral hygiene products for its fresh cooling sensation. Menthol enhances cooling by interacting with the cold-sensitive thermoTRP channel TRPM8, but its effect on pain is less well understood. We presently used behavioral methods to investigate effects of topical menthol on thermal (hot and cold) pain and innocuous cold and mechanical sensitivity in rats. Menthol dose-dependently increased the latency for noxious heat-evoked withdrawal of the treated hindpaw with a weak mirror-image effect, indicating antinociception. Menthol at the highest concentration (40%) reduced mechanical withdrawal thresholds, with no effect at lower concentrations. Menthol had a biphasic effect on cold avoidance. At high concentrations (10% and 40%) menthol reduced avoidance of colder temperatures (15 degrees C and 20 degrees C) compared to 30 degrees C, while at lower concentrations (0.01-1%) menthol enhanced cold avoidance. In a -5 degrees C cold plate test, 40% menthol significantly increased the nocifensive response latency (cold hypoalgesia) while lower concentrations were not different from vehicle controls. These results are generally consistent with neurophysiological and human psychophysical data and support TRPM8 as a potential peripheral target of pain modulation.
authors.affiliation: Section of Neurobiology, Physiology and Behavior, University of California, 1 Shields Ave., Davis, CA 95616, USA.
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Klein
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Sawyer
authors.forename: Mirela Iodi
authors.initials: MI
authors.lastname: Carstens
authors.forename: Merab G
authors.initials: MG
authors.lastname: Tsagareli
authors.forename: Nana
authors.initials: N
authors.lastname: Tsiklauri
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000287:Administration, Topical; D000375:Aging; D000818:Animals; D000982:Antipruritics / Q000008:administration & dosage / Q000494:pharmacology*; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000187:drug effects; D006358:Hot Temperature; D008297:Male; D008610:Menthol / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013697:Thermosensing / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000982:Antipruritics; D008610:Menthol
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