{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T19:22:44Z","timestamp":1769282564261,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,16]],"date-time":"2013-01-16T00:00:00Z","timestamp":1358294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,2]]},"abstract":"Background and Purpose<\/jats:title>The C<\/jats:styled-content>a2+<\/jats:sup>\u2010permeable cation channel TRPV4<\/jats:styled-content> is activated by mechanical disturbance of the cell membrane and is implicated in mechanical hyperalgesia. Nerve growth factor (NGF<\/jats:styled-content>) is increased during inflammation and causes mechanical hyperalgesia. 4\u03b1\u2010phorbol 12,13\u2010didecanoate (4\u03b1PDD<\/jats:styled-content>) has been described as a selective TRPV4<\/jats:styled-content> agonist. We investigated NGF<\/jats:styled-content>\u2010induced hyperalgesia in TRPV4<\/jats:styled-content> wild\u2010type (+\/+) and knockout (\u2013\/\u2013) mice, and the increases in [C<\/jats:styled-content>a2+<\/jats:sup>]i<\/jats:sub> produced by 4\u03b1PDD<\/jats:styled-content> in cultured mouse dorsal root ganglia neurons following exposure to NGF<\/jats:styled-content>.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Withdrawal thresholds to heat, von F<\/jats:styled-content>rey hairs and pressure were measured in mice before and after systemic administration of NGF<\/jats:styled-content>. Changes in intracellular C<\/jats:styled-content>a2+<\/jats:sup> concentration were measured by ratiometric imaging with F<\/jats:styled-content>ura\u20102 in cultured DRG<\/jats:styled-content> and trigeminal ganglia (TG<\/jats:styled-content>) neurons during perfusion of TRPV4<\/jats:styled-content> agonists.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Administration of NGF<\/jats:styled-content> caused a significant sensitization to heat and von Frey stimuli in TRPV4<\/jats:styled-content> +\/+ and \u2013\/\u2013 mice, but only TRPV4<\/jats:styled-content> +\/+ mice showed sensitization to noxious pressure. 4\u03b1PDD<\/jats:styled-content> stimulated a dose\u2010dependent increase in [C<\/jats:styled-content>a2+<\/jats:sup>]i<\/jats:sub> in neurons from +\/+ and \u2013\/\u2013 mice, with the proportion of responding neurons and magnitude of increase unaffected by the genotype. In contrast, the selective TRPV4<\/jats:styled-content> agonist GSK1016790A<\/jats:styled-content> failed to stimulate an increase in intracellular C<\/jats:styled-content>a2+<\/jats:sup> in cultured neurons. Responses to 4\u03b1PDD<\/jats:styled-content> were unaffected by pretreatment with NGF<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>TRPV4<\/jats:styled-content> contributes to mechanosensation in vivo<\/jats:italic>, but there is little evidence for functional TRPV4<\/jats:styled-content> in cultured DRG<\/jats:styled-content> and TG<\/jats:styled-content> neurons. We conclude that 4\u03b1PDD<\/jats:styled-content> activates these neurons independently of TRPV4<\/jats:styled-content>, so it is not appropriate to refer to 4\u03b1PDD<\/jats:styled-content> as a selective TRPV4<\/jats:styled-content> agonist.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2012.02186.x","type":"journal-article","created":{"date-parts":[[2012,8,29]],"date-time":"2012-08-29T02:51:13Z","timestamp":1346208673000},"page":"761-772","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["4\u03b1\u2010phorbol 12,13\u2010didecanoate activates cultured mouse dorsal root ganglia neurons independently of TRPV4<\/scp>"],"prefix":"10.1111","volume":"168","author":[{"given":"R","family":"Alexander","sequence":"first","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Kerby","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AA","family":"Aubdool","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AR","family":"Power","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Grover","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Gentry","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AD","family":"Grant","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5385-05.2006"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4497-07.2008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007759"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.05.024"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00433.2009"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.01.022"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303251200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27624"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-005-1456-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31766"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.161257"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.121111"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00315.2009"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000827"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-37"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00908-X"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00393.2003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.01.021"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.512"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.12.028"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1735416100"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00143-4"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00708.2000"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803970105"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.143370"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.08.002"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0ib00034e"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1111\/j.1476-5381.2010.00873.x","article-title":"Guidelines for reportingexperiments involving animals: the ARRIVE guidelines","volume":"160","author":"McGrath J","journal-title":"Br J Pharmacol"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.207829"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112929"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.166"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.wnr.0000199459.16789.75"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00002.2008"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5793-11.2012"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.03.082"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036318"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302561200"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.139295"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00590.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610485200"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200062200"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208277200"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01807"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.03.008"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.2165\/0063030-200822060-00002"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.134551"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00462.2006"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705443"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00245.2005"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600893"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.12.028"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1476-5381.2012.02186.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1476-5381.2012.02186.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T01:42:41Z","timestamp":1696297361000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2012.02186.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,16]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["10.1111\/j.1476-5381.2012.02186.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1476-5381.2012.02186.x","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,16]]},"assertion":[{"value":"2012-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}