{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:38:17Z","timestamp":1761597497055},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T00:00:00Z","timestamp":1395705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2014,10]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Activation of TRPM<\/jats:styled-content>8 and TRPA<\/jats:styled-content>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<\/jats:styled-content>8 and TRPA<\/jats:styled-content>1 receptors through stimulation of glabrous human skin (volar forearm) by topical administration of 40% L<\/jats:styled-content>\u2010menthol and 10% trans<\/jats:italic>\u2010cinnamaldehyde (CA<\/jats:styled-content>), individually and in combination.<\/jats:p><\/jats:sec>Methods<\/jats:title>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\u2010reflex\u2010flare) in a double\u2010blinded randomized crossover design.<\/jats:p><\/jats:sec>Results<\/jats:title>Cold pain threshold was increased (p<\/jats:italic>\u2009<\u20090.01, cold allodynia) by L<\/jats:styled-content>\u2010menthol alone and L<\/jats:styled-content>\u2010menthol\u2009+\u2009CA<\/jats:styled-content> in combination but unaffected by CA<\/jats:styled-content>. Mechanical pain threshold was significantly decreased (mechanical hyperalgesia) by all three substances (p<\/jats:italic>\u2009<\u20090.01), with a significant intergroup difference found between CA<\/jats:styled-content> alone and the less decreased L<\/jats:styled-content>\u2010menthol\u2009+\u2009CA<\/jats:styled-content> (p<\/jats:italic>\u2009<\u20090.05). Application of CA<\/jats:styled-content> alone and L<\/jats:styled-content>\u2010menthol\u2009+\u2009CA<\/jats:styled-content> in combination showed an increase in skin temperature and perfusion significantly larger than that induced by L<\/jats:styled-content>\u2010menthol alone (p<\/jats:italic>\u2009<\u20090.05). An axon\u2010reflex\u2010flare was present after CA<\/jats:styled-content> administration, but was significantly reduced upon addition of L<\/jats:styled-content>\u2010menthol (p<\/jats:italic>\u2009<\u20090.01).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>This study elucidates the potential of L<\/jats:styled-content>\u2010menthol as a counter\u2010irritant to secondary neurogenic inflammation and provides evidence of an intricate interplay between cold receptors TRPA<\/jats:styled-content>1 and TRPM<\/jats:styled-content>8, warranting further investigation of the neural coding of cold pain perception.<\/jats:p><\/jats:sec>","DOI":"10.1002\/j.1532-2149.2014.494.x","type":"journal-article","created":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T08:16:57Z","timestamp":1395735417000},"page":"1333-1342","source":"Crossref","is-referenced-by-count":45,"title":["Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM<\/scp>8 and TRPA<\/scp>1 using topical L<\/scp>\u2010menthol and trans<\/i>\u2010cinnamaldehyde in healthy volunteers"],"prefix":"10.1002","volume":"18","author":[{"given":"R.V.","family":"Olsen","sequence":"first","affiliation":[{"name":"Center for Sensory\u2010Motor Interaction (SMI) Department of Health Science and Technology Faculty of Medicine Aalborg University Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.H.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Center for Sensory\u2010Motor Interaction (SMI) Department of Health Science and Technology Faculty of Medicine Aalborg University Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.G.","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Center for Sensory\u2010Motor Interaction (SMI) Department of Health Science and Technology Faculty of Medicine Aalborg University Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.W.","family":"Eskelund","sequence":"additional","affiliation":[{"name":"Center for Sensory\u2010Motor Interaction (SMI) Department of Health Science and Technology Faculty of Medicine Aalborg University Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Arendt\u2010Nielsen","sequence":"additional","affiliation":[{"name":"Center for Sensory\u2010Motor Interaction (SMI) Department of Health Science and Technology Faculty of Medicine Aalborg University Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1532-2149.2013.00380.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1532-2149.2012.00239.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03695.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/00002508-200006001-00004","article-title":"Peripheral neuropathic pain: From mechanisms to symptoms","volume":"16","author":"Baron R.","year":"2000","journal-title":"Clin J Pain"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neucli.2012.06.002"},{"key":"e_1_2_9_7_1","first-page":"655","article-title":"TRP channel antagonists for pain \u2013 Opportunities beyond TRPV1","volume":"10","author":"Bevan S.","year":"2009","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2010.12.013"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.03.081"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11362-Z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.06.089"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.04.017"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8023144"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(02)00043-X"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.02.012"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1994.tb03871.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1696-08.2008"},{"key":"e_1_2_9_18_1","first-page":"42324","article-title":"External analgesic drug products for over\u2010the\u2010counter human use; 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