Felix J Resch, Stefan Heber, Farzin Shahi, Manuel Zauner, Cosmin I Ciotu, Andreas Gleiss, Sabine Sator, Michael J M Fischer
{"title":"Human cold pain: a randomized crossover trial.","authors":"Felix J Resch, Stefan Heber, Farzin Shahi, Manuel Zauner, Cosmin I Ciotu, Andreas Gleiss, Sabine Sator, Michael J M Fischer","doi":"10.1097/j.pain.0000000000003503","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>The mechanism causing cold pain in humans is unresolved. Animal data suggest a nonredundant contribution to cold pain for transient receptor potential channels TRPM8 and TRPA1 for detection and voltage-gated sodium channels NaV1.7 and NaV1.8 for conduction at these temperatures. We established an intradermal injection-based cold pain model, which allows pharmacologically addressing molecular targets at the site of cooling. Lidocaine, added to the injection solution as positive control, largely reduced cold-induced pain in 36 volunteers. The 4 mentioned molecular targets were blocked by antagonists in a double-blinded crossover trial. Pain induced by 3°C intradermal fluid was not reduced to a relevant extent by any of the 4 antagonists alone or by the quadruple combination. However, the temperature threshold for cold pain appeared shifted by the inhibition of TRPA1, TRPM8, and NaV1.7 and to a lesser extent by NaV1.8 inhibition, 4-fold inhibition decreased the threshold by 5.8°C. Further mechanisms contributing to human cold pain need to be considered.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9000,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PAIN®","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/j.pain.0000000000003503","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: The mechanism causing cold pain in humans is unresolved. Animal data suggest a nonredundant contribution to cold pain for transient receptor potential channels TRPM8 and TRPA1 for detection and voltage-gated sodium channels NaV1.7 and NaV1.8 for conduction at these temperatures. We established an intradermal injection-based cold pain model, which allows pharmacologically addressing molecular targets at the site of cooling. Lidocaine, added to the injection solution as positive control, largely reduced cold-induced pain in 36 volunteers. The 4 mentioned molecular targets were blocked by antagonists in a double-blinded crossover trial. Pain induced by 3°C intradermal fluid was not reduced to a relevant extent by any of the 4 antagonists alone or by the quadruple combination. However, the temperature threshold for cold pain appeared shifted by the inhibition of TRPA1, TRPM8, and NaV1.7 and to a lesser extent by NaV1.8 inhibition, 4-fold inhibition decreased the threshold by 5.8°C. Further mechanisms contributing to human cold pain need to be considered.
期刊介绍:
PAIN® is the official publication of the International Association for the Study of Pain and publishes original research on the nature,mechanisms and treatment of pain.PAIN® provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.