{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:55:23Z","timestamp":1787864123409,"version":"build-2784847793"},"reference-count":51,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T00:00:00Z","timestamp":1557964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1072113"],"award-info":[{"award-number":["APP1072113"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>T\u2010type calcium (Ca<jats:sub>v<\/jats:sub>3) and transient receptor potential vanilloid\u20101 (TRPV1) channels play central roles in the control of excitability in the peripheral nervous system and are regarded as potential therapeutic pain targets. Modulators that either activate or inhibit TRPV1\u2010mediated currents display analgesic properties in various pain models despite opposing effects on their connate target, TRPV1. We explored the effects of TRPV1\u2010active compounds on Ca<jats:sub>v<\/jats:sub>3\u2010mediated currents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Whole\u2010cell patch clamp recordings were used to examine the effects of TRPV1\u2010active compounds on rat dorsal root ganglion low voltage\u2010activated calcium currents and recombinant Ca<jats:sub>v<\/jats:sub>3 isoforms in expression systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The classical TRPV1 agonist capsaicin as well as TRPV1 antagonists A\u2010889425, BCTC, and capsazepine directly inhibited Ca<jats:sub>v<\/jats:sub>3 channels. These compounds altered the voltage\u2010dependence of activation and inactivation of Ca<jats:sub>v<\/jats:sub>3 channels and delayed their recovery from inactivation, leading to a concomitant decrease in T\u2010type current availability. The TRPV1 antagonist capsazepine potently inhibited Ca<jats:sub>v<\/jats:sub>3.1 and 3.2 channels (<jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub>\u00a0&lt;\u00a0120\u00a0nM), as demonstrated by its slow off rate. In contrast, neither the TRPV1 agonists, Palvanil and resiniferatoxin, nor the TRPV1 antagonist AMG9810 modulated Ca<jats:sub>v<\/jats:sub>3\u2010mediated currents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Analgesic TRPV1\u2010active compounds inhibit Ca<jats:sub>v<\/jats:sub>3 currents in native and heterologous systems. Hence, their analgesic effects may not be exclusively attributed to their actions on TRPV1, which has important implications in the current understanding of nociceptive pathways. Importantly, our results highlight the need for attention in the experimental design used to address the analgesic properties of Ca<jats:sub>v<\/jats:sub>3 channel inhibitors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14676","type":"journal-article","created":{"date-parts":[[2019,3,30]],"date-time":"2019-03-30T07:58:31Z","timestamp":1553932711000},"page":"2264-2278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Analgesic transient receptor potential vanilloid\u20101\u2010active compounds inhibit native and recombinant T\u2010type calcium channels"],"prefix":"10.1111","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2546-7913","authenticated-orcid":false,"given":"Jeffrey R.","family":"McArthur","sequence":"first","affiliation":[{"name":"Illawarra Health and Medical Research Institute University of Wollongong  Wollongong NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-4532","authenticated-orcid":false,"given":"Rocio K.","family":"Finol\u2010Urdaneta","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute University of Wollongong  Wollongong NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7030-2288","authenticated-orcid":false,"given":"David J.","family":"Adams","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute University of Wollongong  Wollongong NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13884"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb12781.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600515"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph5020114"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.4.6.14106"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12823"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07456.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.74.5.1870"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.02.144"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/39807"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.4.7"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.22331"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.08.031"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.7033"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610033200"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600418113"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-011-1023-5"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.1.103"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"issue":"9","key":"e_1_2_12_21_1","first-page":"CD010111","article-title":"Topical capsaicin (low concentration) for chronic neuropathic pain in adults","author":"Derry S.","year":"2012","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701272"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.086199"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.042"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02047.x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(02)75164-3"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.09.033"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01031.2007"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4866-06.2007"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100129497"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918765808"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.01.015"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200809986"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018550108"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100869108"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13910"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90768.2008"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703918"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14044"},{"key":"e_1_2_12_42_1","first-page":"702","article-title":"NGX\u20104010, a high\u2010concentration capsaicin dermal patch for lasting relief of peripheral neuropathic pain","volume":"10","author":"Noto C.","year":"2009","journal-title":"Current Opinion in Investigational Drugs"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091467"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.079277"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2008.00072.x"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.551473"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13906"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02732"},{"key":"e_1_2_12_49_1","first-page":"551","article-title":"A randomized, double\u2010blind, placebo\u2010controlled, crossover study of the T\u2010type calcium channel blocker ABT\u2010639 in an intradermal capsaicin experimental pain model in healthy adults","volume":"17","author":"Wallace M.","year":"2016","journal-title":"Pain Medicine"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1159\/000276981"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501229200"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e318272fbf8"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14676","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.14676","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14676","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T17:57:31Z","timestamp":1694368651000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,16]]},"references-count":51,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1111\/bph.14676"],"URL":"https:\/\/doi.org\/10.1111\/bph.14676","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,16]]},"assertion":[{"value":"2018-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}