{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T21:08:07Z","timestamp":1769720887991,"version":"3.49.0"},"reference-count":63,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T00:00:00Z","timestamp":1543536000000},"content-version":"am","delay-in-days":290,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T00:00:00Z","timestamp":1518480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["ARC) Discovery Early Career Research Award"],"award-info":[{"award-number":["ARC) Discovery Early Career Research Award"]}],"id":[{"id":"10.13039\/501100000923","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":[[2018,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Patients with irritable bowel syndrome suffer from chronic visceral pain (CVP) and limited analgesic therapeutic options are currently available. We have shown that \u03b1\u2010conotoxin Vc1.1 induced activation of GABA<jats:sub>B<\/jats:sub> receptors on the peripheral endings of colonic afferents and reduced nociceptive signalling from the viscera. However, the analgesic efficacy of more stable, cyclized versions of Vc1.1 on CVP remains to be determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Using <jats:italic>ex vivo<\/jats:italic> colonic afferent preparations from mice, we determined the inhibitory actions of cyclized Vc1.1 (cVc1.1) and two cVc1.1 analogues on mouse colonic nociceptors in healthy and chronic visceral hypersensitivity (CVH) states. Using whole\u2010cell patch clamp recordings, we also assessed the inhibitory actions of these peptides on the neuronal excitability of colonic innervating dorsal root ganglion neurons. <jats:italic>In vivo,<\/jats:italic> the analgesic efficacy of these analogues was assessed by determining the visceromotor response to colorectal distension in healthy and CVH mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>cVc1.1 and the cVc1.1 analogues, [C2H,C8F]cVc1.1 and [N9W]cVc1.1, all caused concentration\u2010dependent inhibition of colonic nociceptors from healthy mice. Inhibition by these peptides was greater than those evoked by linear Vc1.1 and was substantially greater in colonic nociceptors from CVH mice. cVc1.1 also reduced excitability of colonic dorsal root ganglion neurons, with greater effect in CVH neurons. CVH mice treated with cVc1.1 intra\u2010colonically displayed reduced pain responses to noxious colorectal distension compared with vehicle\u2010treated CVH mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Cyclic versions of Vc1.1 evoked significant anti\u2010nociceptive actions in CVH states, suggesting that they could be novel candidates for treatment of CVP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.12\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.12\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14115","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T14:06:36Z","timestamp":1512050796000},"page":"2384-2398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Cyclic analogues of \u03b1\u2010conotoxin Vc1.1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal pain"],"prefix":"10.1111","volume":"175","author":[{"given":"Joel","family":"Castro","sequence":"first","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke","family":"Grundy","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemie","family":"Deiteren","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea M","family":"Harrington","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Maddern","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessi","family":"Moore","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Garcia\u2010Caraballo","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grigori Y","family":"Rychkov","sequence":"additional","affiliation":[{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rilei","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience University of Queensland  Brisbane QLD 4072 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quentin","family":"Kaas","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience University of Queensland  Brisbane QLD 4072 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J","family":"Craik","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience University of Queensland  Brisbane QLD 4072 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 (IHMRI) University of Wollongong  Wollongong NSW 2522 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2527-2905","authenticated-orcid":false,"given":"Stuart M","family":"Brierley","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health Flinders University  Bedford Park South Australia 5042 Australia"},{"name":"Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI)  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.02.029"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2013.01.019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01781.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13884"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13879"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0307-07.2007"},{"key":"e_1_2_10_9_1","unstructured":"ASX(2006a).Metabolic Pharmaceuticals: metabolics neuropathic pain drug ACV1\u2010additional preclinical studies reveal greater potential.http:\/\/wwwasxcomau\/asxpdf\/20061123\/pdf\/3zqm91n1jhpffpdf."},{"key":"e_1_2_10_10_1","unstructured":"ASX(2006b).Metabolic Pharmaceuticals: metabolics neuropathic pain drug ACV1\u2010 Clinical trials update.http:\/\/wwwasxcomau\/asxpdf\/20061129\/pdf\/3zv2c96tyh1nxpdf."},{"key":"e_1_2_10_11_1","unstructured":"ASX(2007).Metabolic Pharmaceuticals: metabolic discontinues clinical trial programme for neuropathic pain drug ACV1.http:\/\/wwwasxcomau\/asxpdf\/20070814\/pdf\/313yjgpf7jl4lgpdf."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560070808"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.034"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201311104"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2009.07.019"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-27592-5_9"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2014.103"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.008"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2005.00710.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.089714"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.074"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.07.048"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.206789"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.29"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.4.1.10281"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3594-08.2008"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20681"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201600297"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.08.017"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310971"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.0954"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.392"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604550200"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201000620"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4165"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305870"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.14"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(99)00165-X"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23042"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2009.05248.x"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.170811"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301856"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-306240"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.096156"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi801998a"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.09.007"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002252200"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.05.020"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins7103916"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)91555-7"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17976"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi991282m"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.08.009"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.12.70"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.12.024"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802612802652457"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.11.7.891"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608715103"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400041h"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13264"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.14115","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14115","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.14115","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/bph.14115","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T14:52:12Z","timestamp":1694530332000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,13]]},"references-count":63,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/bph.14115"],"URL":"https:\/\/doi.org\/10.1111\/bph.14115","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,13]]},"assertion":[{"value":"2017-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}