title: Wu-tou decoction inhibits chronic inflammatory pain in mice: participation of TRPV1 and TRPA1 ion channels.
abstract: Wu-tou decoction (WTD) is a classic traditional Chinese medicine formula and has been used effectively to treat joint diseases clinically. Previous reports indicated that WTD possesses anti-inflammatory activity; however, its actions on pain have not been clarified. Here, we investigated the antinociceptive activity of WTD in CFA-induced mice, and its possible mechanism of the action associated with transient receptor potential (TRP) ion channels was also explored. Our results showed that 1.58, 3.15, and 6.30 g/kg WTD significantly attenuated mechanical, cold, and heat hypersensitivities. Moreover, WTD effectively inhibited spontaneous nociceptive responses to intraplantar injections of capsaicin and cinnamaldehyde, respectively. WTD also effectively suppressed jumping and wet-dog-shake behaviors to intraperitoneal injection of icilin. Additionally, WTD significantly reduced protein expression of TRPV1 and TRPA1 in dorsal root ganglia and skins of injured paw. Collectively, our data demonstrate firstly that WTD exerts antinociceptive activity in inflammatory conditions by attenuating mechanical, cold, and heat hypersensitivities. This antinociceptive effect may result in part from inhibiting the activities of TRPV1, TRPA1, and TRPM8, and the suppression of TRPV1 and TRPA1 protein by WTD was also highly effective. These findings suggest that WTD might be an attractive and suitable therapeutic agent for the management of chronic inflammatory pain.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Hongye
authors.initials: H
authors.lastname: Wan
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Danhua
authors.identifier: 0000-0002-9202-5939
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Danni
authors.initials: D
authors.lastname: Sun
authors.affiliation: National Center for Mass Spectrometry in Changchun & Jilin Province Key Laboratory for Traditional Chinese Medicine Chemistry and Mass Spectrometry & Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China ; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Xu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute Acupuncture & Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Jing
authors.affiliation: Institute Acupuncture & Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute Acupuncture & Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Chen
authors.affiliation: National Center for Mass Spectrometry in Changchun & Jilin Province Key Laboratory for Traditional Chinese Medicine Chemistry and Mass Spectrometry & Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Na
authors.identifier: 0000-0001-9630-1497
authors.initials: N
authors.lastname: Lin
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008516:Medicine, Chinese Traditional / Q000379:methods; D051379:Mice; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D000700:Analgesics; D004365:Drugs, Chinese Herbal; D007473:Ion Channels; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse
references.citation: Br J Pharmacol. 2014 May;171(10):2508-27
references.pmid: 24283624
references.citation: Pain Pract. 2010 May-Jun;10(3):185-200
references.pmid: 20230457
references.citation: J Ethnopharmacol. 2014 Apr 11;153(1):160-8
references.pmid: 24530855
references.citation: J Pharmacol Exp Ther. 2003 Jan;304(1):56-62
references.pmid: 12490575
references.citation: Zhongguo Zhong Yao Za Zhi. 2010 Apr;35(8):1025-9
references.pmid: 20617686
references.citation: J Pain. 2010 Nov;11(11):1222-9
references.pmid: 20452289
references.citation: J Neurosci Methods. 1994 Jul;53(1):55-63
references.pmid: 7990513
references.citation: Eur J Pain. 2012 Apr;16(4):485-95
references.pmid: 22396078
references.citation: Nature. 2000 May 11;405(6783):183-7
references.pmid: 10821274
references.citation: Eur J Pharmacol. 2013 Sep 15;716(1-3):61-76
references.pmid: 23500195
references.citation: J Dent Res. 2007 Jun;86(6):550-5
references.pmid: 17525356
references.citation: Pain. 2010 Mar;148(3):431-7
references.pmid: 20056530
references.citation: Nat Neurosci. 2002 Nov;5 Suppl:1062-7
references.pmid: 12403987
references.citation: Neurosci Lett. 2011 May 20;495(3):173-7
references.pmid: 21315136
references.citation: Neuron. 2002 Sep 26;36(1):57-68
references.pmid: 12367506
references.citation: J Pharmacol Exp Ther. 1999 Apr;289(1):417-26
references.pmid: 10087033
references.citation: Arthritis Rheum. 2011 Mar;63(3):819-29
references.pmid: 21360511
references.citation: Biochim Biophys Acta. 2007 Aug;1772(8):989-1003
references.pmid: 17321113
references.citation: Cell. 2009 Jun 12;137(6):987-8
references.pmid: 19524498
references.citation: J Clin Invest. 2005 Sep;115(9):2393-401
references.pmid: 16110328
references.citation: Toxicology. 2000 Apr 3;144(1-3):205-10
references.pmid: 10781889
references.citation: Pain. 2005 Dec 15;119(1-3):1-4
references.pmid: 16298492
references.citation: Science. 2000 Apr 14;288(5464):306-13
references.pmid: 10764638
references.citation: Pain Med. 2009 May-Jun;10(4):654-62
references.pmid: 19302436
references.citation: Eur J Pharmacol. 2006 Oct 10;547(1-3):101-5
references.pmid: 16945367
references.citation: Neuron. 2007 May 3;54(3):379-86
references.pmid: 17481392
references.citation: Talanta. 2014 Jan;118:21-9
references.pmid: 24274266
references.citation: J Pharmacol Exp Ther. 2005 Feb;312(2):726-32
references.pmid: 15494550
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Mar 15;953-954:11-9
references.pmid: 24561351
references.citation: Pharmacology. 2010;85(3):188-93
references.pmid: 20185968
references.citation: Pain. 1988 Jan;32(1):77-88
references.pmid: 3340425
references.citation: PLoS One. 2013;8(7):e67730
references.pmid: 23861794
references.citation: Eur J Pain. 1998 Mar;2(1):63-68
references.pmid: 10700302
references.citation: PLoS One. 2011;6(9):e25894
references.pmid: 21984952
references.citation: Cell. 2003 Mar 21;112(6):819-29
references.pmid: 12654248
references.citation: Pain. 2012 Jun;153(6):1167-79
references.pmid: 22414871
references.citation: Nat Neurosci. 2012 Aug;15(8):1063-7
references.pmid: 22837035
references.citation: Br J Pharmacol. 1997 Jun;121(3):417-24
references.pmid: 9179382