{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:12:20Z","timestamp":1791209540437,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T00:00:00Z","timestamp":1415836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003837","name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care","doi-asserted-by":"crossref","award":["H20-23"],"award-info":[{"award-number":["H20-23"]}],"id":[{"id":"10.13039\/501100003837","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004051","name":"Kato Memorial Bioscience Foundation","doi-asserted-by":"crossref","award":["H21-20"],"award-info":[{"award-number":["H21-20"]}],"id":[{"id":"10.13039\/501100004051","id-type":"DOI","asserted-by":"crossref"}]},{"name":"KEIRYOKAI research foundation","award":["H22-109"],"award-info":[{"award-number":["H22-109"]}]},{"name":"MEXT-Supported Program for the Strategic Research Foundation at Private Universities","award":["2010-2014"],"award-info":[{"award-number":["2010-2014"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["24700383"],"award-info":[{"award-number":["24700383"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"crossref","award":["H21-29"],"award-info":[{"award-number":["H21-29"]}],"id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:p>Levo\u2010tetrahydropalmatine (<jats:italic>l<\/jats:italic>\u2010THP), a main bioactive Chinese herbal constituent from the genera <jats:italic>Stephania<\/jats:italic> and <jats:italic>Corydalis<\/jats:italic>, has been in use in clinical practice for years in China as a traditional analgesic agent. However, the mechanism underlying the analgesic action of <jats:italic>l<\/jats:italic>\u2010THP is poorly understood. This study shows that <jats:italic>l<\/jats:italic>\u2010THP can exert an inhibitory effect on the functional activity of native acid\u2010sensing ion channels (ASICs), which are believed to mediate pain caused by extracellular acidification. <jats:italic>l<\/jats:italic>\u2010THP dose dependently decreased the amplitude of proton\u2010gated currents mediated by ASICs in rat dorsal root ganglion (DRG) neurons. <jats:italic>l<\/jats:italic>\u2010THP shifted the proton concentration\u2013response curve downward, with a decrease of 40.93%\u2009\u00b1\u20098.45% in the maximum current response to protons, with no significant change in the pH<jats:sub>0.5<\/jats:sub> value. Moreover, <jats:italic>l<\/jats:italic>\u2010THP can alter the membrane excitability of rat DRG neurons to acid stimuli. It significantly decreased the number of action potentials and the amplitude of the depolarization induced by an extracellular pH drop. Finally, peripherally administered <jats:italic>l<\/jats:italic>\u2010THP inhibited the nociceptive response to intraplantar injection of acetic acid in rats. These results indicate that <jats:italic>l<\/jats:italic>\u2010THP can inhibit the functional activity of ASICs in dissociated primary sensory neurons and relieve acidosis\u2010evoked pain in vivo, which for the first time provides a novel peripheral mechanism underlying the analgesic action of <jats:italic>l<\/jats:italic>\u2010THP. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23484","type":"journal-article","created":{"date-parts":[[2014,11,14]],"date-time":"2014-11-14T05:09:37Z","timestamp":1415941777000},"page":"333-339","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of acid\u2010sensing ion channels by levo\u2010tetrahydropalmatine in rat dorsal root ganglion neurons"],"prefix":"10.1002","volume":"93","author":[{"given":"Ting\u2010Ting","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Ion Channels, Department of Pharmacology Hubei University of Science and Technology Hubei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu\u2010Wei","family":"Qu","sequence":"additional","affiliation":[{"name":"Institute of Ion Channels, Department of Pharmacology Hubei University of Science and Technology Hubei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Yu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Institute of Ion Channels, Department of Pharmacology Hubei University of Science and Technology Hubei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Institute of Ion Channels, Department of Pharmacology Hubei University of Science and Technology Hubei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuixia","family":"Ren","sequence":"additional","affiliation":[{"name":"Institute of Ion Channels, Department of Pharmacology Hubei University of Science and Technology Hubei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Gan","sequence":"additional","affiliation":[{"name":"Institute of Ion Channels, Department of Pharmacology Hubei University of Science and Technology Hubei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Ion Channels, Department of Pharmacology Hubei University of Science and Technology Hubei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang\u2010Ping","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Ion Channels, Department of Pharmacology Hubei University of Science and Technology Hubei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042688199"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032678399"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(94)90149-X"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.08.016"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00322-5"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-007-9179-4"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.213"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.08.006"},{"key":"e_1_2_6_10_1","first-page":"225","article-title":"Characteristics of tetrahydroprotoberberines on dopamine D1 and D2 receptors in calf striatum","volume":"18","author":"Guo X","year":"1997","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"e_1_2_6_11_1","first-page":"193","article-title":"Effect of tetrahydropalmatine analogs on Fos expression induced by formalin pain","volume":"20","author":"Hu JY","year":"1999","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"e_1_2_6_12_1","first-page":"715","article-title":"Supraspinal D2 receptor involved in antinociception induced by l\u2010tetrahydropalmatine","volume":"20","author":"Hu JY","year":"1999","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"e_1_2_6_13_1","first-page":"439","article-title":"Arcuate nucleus of hypothalamus involved in analgesic action of l\u2010THP","volume":"21","author":"Hu JY","year":"2000","journal-title":"Acta Pharmacol Sin"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.01.020"},{"key":"e_1_2_6_15_1","first-page":"47","article-title":"Studies on the pharmacological actions of corydalis. Xii. The effects of optical isomers of tetrahydropalmatine (THP) on the central nervous system","volume":"27","author":"Kin KC","year":"1964","journal-title":"Sheng Li Xue Bao"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-9-27"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2010.03.005"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3191-03.2004"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb01769.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)02323-0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-24-10662.2002"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-0754-7"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.03.040"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.113035"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00547-5"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-108"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.04.034"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.12.017"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1986.104"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-01-00086.1992"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)03318-3"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215709"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-009-3409-1"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3376-12.2013"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3529"},{"key":"e_1_2_6_36_1","first-page":"217","article-title":"Relevance of brain prostaglandins to central effects of l\u2010tetrahydropalmatine","volume":"3","author":"Xu J","year":"1982","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-6-1"},{"key":"e_1_2_6_38_1","first-page":"522","article-title":"Effects of l\u2010stepholidine on the central nervous and cardiovascular systems","volume":"7","author":"Zhang ZD","year":"1986","journal-title":"Zhongguo Yao Li Xue Bao"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.23484","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.23484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T17:09:37Z","timestamp":1696352977000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.23484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,13]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1002\/jnr.23484"],"URL":"https:\/\/doi.org\/10.1002\/jnr.23484","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,13]]}}}