title: A clinical and mechanistic study of topical borneol-induced analgesia.
abstract: Bingpian is a time-honored herb in traditional Chinese medicine (TCM). It is an almost pure chemical with a chemical composition of (+)-borneol and has been historically used as a topical analgesic for millennia. However, the clinical efficacy of topical borneol lacks stringent evidence-based clinical studies and verifiable scientific mechanism. We examined the analgesic efficacy of topical borneol in a randomized, double-blind, placebo-controlled clinical study involving 122 patients with postoperative pain. Topical application of borneol led to significantly greater pain relief than placebo did. Using mouse models of pain, we identified the TRPM8 channel as a molecular target of borneol and showed that topical borneol-induced analgesia was almost exclusively mediated by TRPM8, and involved a downstream glutamatergic mechanism in the spinal cord. Investigation of the actions of topical borneol and menthol revealed mechanistic differences between borneol- and menthol-induced analgesia and indicated that borneol exhibits advantages over menthol as a topical analgesic. Our work demonstrates that borneol, which is currently approved by the US FDA to be used only as a flavoring substance or adjuvant in food, is an effective topical pain reliever in humans and reveals a key part of the molecular mechanism underlying its analgesic effect.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China wangshu@mail.kiz.ac.cn shu_wang@outlook.com jy160@columbia.edu jianyang@mail.kiz.ac.cn jianruxiao83@163.com.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
authors.forename: Shu
authors.identifier: 0000-0001-6383-3411
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Oncology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Orthopedic Oncology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Department of Orthopedic Oncology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
authors.forename: Deyuan
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Preventive Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Hualing
authors.initials: H
authors.lastname: Song
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.|Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Cui
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.|Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China wangshu@mail.kiz.ac.cn shu_wang@outlook.com jy160@columbia.edu jianyang@mail.kiz.ac.cn jianruxiao83@163.com.|Department of Biological Sciences, Columbia University, New York, NY, USA.
authors.forename: Jian
authors.identifier: 0000-0003-0290-7688
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Oncology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China wangshu@mail.kiz.ac.cn shu_wang@outlook.com jy160@columbia.edu jianyang@mail.kiz.ac.cn jianruxiao83@163.com.
authors.forename: Jianru
authors.identifier: 0000-0003-1547-851X
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000287:Administration, Topical; D000698:Analgesia / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001892:Camphanes / Q000008:administration & dosage*; D004311:Double-Blind Method; D006801:Humans; D051379:Mice; D010919:Placebos / Q000008:administration & dosage; D050053:TRPM Cation Channels / Q000378:metabolism
chemical_list: D000700:Analgesics; D001892:Camphanes; D010919:Placebos; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; C022871:isoborneol
keywords: TRPM8; borneol; pain; topical analgesic; traditional Chinese medicine