{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T21:03:26Z","timestamp":1768251806251,"version":"3.49.0"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","medical-hypotheses.com","clinicalkey.com","clinicalkey.es","clinicalkey.fr","clinicalkey.com.au","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Medical Hypotheses"],"published-print":{"date-parts":[[2018,1]]},"DOI":"10.1016\/j.mehy.2017.11.002","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T15:46:09Z","timestamp":1509983169000},"page":"86-89","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":36,"special_numbering":"C","title":["The pruritus of cholestasis: From bile acids to opiate agonists: Relevant after all these years"],"prefix":"10.1016","volume":"110","author":[{"given":"Nora V.","family":"Bergasa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.mehy.2017.11.002_b0005","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/hep.1840110526","article-title":"The pruritus of cholestasis: from bile acids to opiate agonists","volume":"11","author":"Jones","year":"1990","journal-title":"Hepatology"},{"issue":"6662","key":"10.1016\/j.mehy.2017.11.002_b0010","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1136\/bmj.297.6662.1501","article-title":"Opioid peptides and primary biliary cirrhosis","volume":"297","author":"Thornton","year":"1988","journal-title":"Br Med J"},{"issue":"2","key":"10.1016\/j.mehy.2017.11.002_b0015","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/0016-5085(92)90102-5","article-title":"A controlled trial of naloxone infusions for the pruritus of chronic cholestasis","volume":"102","author":"Bergasa","year":"1992","journal-title":"Gastroenterology"},{"issue":"4","key":"10.1016\/j.mehy.2017.11.002_b0020","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S1085-5629(05)80052-5","article-title":"The pruritus of cholestasis","volume":"14","author":"Bergasa","year":"1995","journal-title":"Semin Dermatol"},{"key":"10.1016\/j.mehy.2017.11.002_b0025","first-page":"1022","article-title":"Pilot study of the use of naltrexone to treat the severe pruritus of cholestatic liver disease","volume":"91","author":"Carson","year":"1996","journal-title":"Am J Gastroenterol"},{"issue":"4","key":"10.1016\/j.mehy.2017.11.002_b0030","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/gast.1997.v113.pm9322521","article-title":"Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study","volume":"113","author":"Wolfhagen","year":"1997","journal-title":"Gastroenterology"},{"issue":"3","key":"10.1016\/j.mehy.2017.11.002_b0035","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/hep.510270307","article-title":"Open-label trial of oral nalmefene therapy for the pruritus of cholestasis","volume":"27","author":"Bergasa","year":"1998","journal-title":"Hepatology"},{"issue":"3 Pt 1","key":"10.1016\/j.mehy.2017.11.002_b0040","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0190-9622(99)70117-9","article-title":"Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis: a controlled study","volume":"41","author":"Bergasa","year":"1999","journal-title":"J Am Acad Dermatol"},{"issue":"6","key":"10.1016\/j.mehy.2017.11.002_b0045","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0168-8278(02)00318-5","article-title":"Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study","volume":"37","author":"Terg","year":"2002","journal-title":"J Hepatol"},{"issue":"7","key":"10.1016\/j.mehy.2017.11.002_b0050","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3748\/wjg.v12.i7.1125","article-title":"Effect of oral naltrexone on pruritus in cholestatic patients","volume":"12","author":"Mansour-Ghanaei","year":"2006","journal-title":"World J Gastroenterol"},{"issue":"6","key":"10.1016\/j.mehy.2017.11.002_b0055","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1097\/MPG.0b013e3181eb5ac0","article-title":"Use of oral naltrexone for severe pruritus due to cholestatic liver disease in children","volume":"51","author":"Zellos","year":"2010","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"5","key":"10.1016\/j.mehy.2017.11.002_b0060","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1016\/j.clinre.2015.08.001","article-title":"Changing nomenclature for PBC: From 'cirrhosis' to 'cholangitis'","volume":"39","author":"Beuers","year":"2015","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"2","key":"10.1016\/j.mehy.2017.11.002_b0065","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0304-3959(88)90085-1","article-title":"Itching after epidural and spinal opiates","volume":"33","author":"Ballantyne","year":"1988","journal-title":"Pain"},{"issue":"10","key":"10.1016\/j.mehy.2017.11.002_b0070","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/j.1365-2044.1989.tb09116.x","article-title":"The incidence of pruritus after epidural morphine","volume":"44","author":"Ballantyne","year":"1989","journal-title":"Anaesthesia"},{"issue":"2","key":"10.1016\/j.mehy.2017.11.002_b0075","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0006-8993(95)00871-M","article-title":"Microinjection of morphine into the rat medullary dorsal horn produces a dose-dependent increase in facial scratching","volume":"695","author":"Thomas","year":"1995","journal-title":"Brain Res"},{"issue":"1","key":"10.1016\/j.mehy.2017.11.002_b0080","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1124\/jpet.102.044909","article-title":"Activation of kappa-opioid receptors inhibits pruritus evoked by subcutaneous or intrathecal administration of morphine in monkeys","volume":"305","author":"Ko","year":"2003","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"10.1016\/j.mehy.2017.11.002_b0085","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1124\/jpet.103.061101","article-title":"The role of central mu opioid receptors in opioid-induced itch in primates","volume":"310","author":"Ko","year":"2004","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"10.1016\/j.mehy.2017.11.002_b0090","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0168-8278(05)80471-4","article-title":"Cholestasis in the male rat is associated with naloxone-reversible antinociception","volume":"20","author":"Bergasa","year":"1994","journal-title":"J Hepatol"},{"issue":"1\u20132","key":"10.1016\/j.mehy.2017.11.002_b0095","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/0168-8278(92)90040-V","article-title":"Central mu-opioid receptors are down-regulated in a rat model of cholestasis","volume":"15","author":"Bergasa","year":"1992","journal-title":"J Hepatol"},{"issue":"2 Pt 1","key":"10.1016\/j.mehy.2017.11.002_b0100","first-page":"G346","article-title":"Cholestasis is associated with preproenkephalin mRNA expression in the adult rat liver","volume":"268","author":"Bergasa","year":"1995","journal-title":"Am J Physiol"},{"issue":"5","key":"10.1016\/j.mehy.2017.11.002_b0105","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1600-0676.1996.tb00749.x","article-title":"Hepatic concentrations of proenkephalin-derived opioids are increased in a rat model of cholestasis","volume":"16","author":"Bergasa","year":"1996","journal-title":"Liver"},{"issue":"2","key":"10.1016\/j.mehy.2017.11.002_b0110","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/0016-5085(92)90857-U","article-title":"Endogenous opioids accumulate in plasma in a rat model of acute cholestasis","volume":"103","author":"Swain","year":"1992","journal-title":"Gastroenterology"},{"issue":"11","key":"10.1016\/j.mehy.2017.11.002_b0115","first-page":"2018","article-title":"Methionine-enkephalin concentrations correlate with stage of disease but not pruritus in patients with primary biliary cirrhosis","volume":"89","author":"Spivey","year":"1994","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"10.1016\/j.mehy.2017.11.002_b0120","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1034\/j.1600-0676.2002.01458.x","article-title":"Hepatic Met-enkephalin immunoreactivity is enhanced in primary biliary cirrhosis","volume":"22","author":"Bergasa","year":"2002","journal-title":"Liver"},{"issue":"3","key":"10.1016\/j.mehy.2017.11.002_b0125","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S1665-2681(19)31851-4","article-title":"Human hepatic met-enkephalin and delta opioid receptor-1 immunoreactivities in viral and autoimmune hepatitis","volume":"7","author":"Boyella","year":"2008","journal-title":"Ann Hepatol"},{"issue":"1","key":"10.1016\/j.mehy.2017.11.002_b0130","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0168-8278(89)90161-X","article-title":"Methionine enkephalin is increased in plasma in acute liver disease and is present in bile and urine","volume":"8","author":"Thornton","year":"1989","journal-title":"J Hepatol"},{"issue":"3","key":"10.1016\/j.mehy.2017.11.002_b0135","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0304-3940(01)01640-8","article-title":"Uptake and efflux of the peptidic delta-opioid receptor agonist","volume":"301","author":"Dagenais","year":"2001","journal-title":"Neurosci Lett"},{"issue":"1 Pt 1","key":"10.1016\/j.mehy.2017.11.002_b0140","first-page":"E1","article-title":"Peptide transport systems for opiates across the blood-brain barrier","volume":"259","author":"Banks","year":"1990","journal-title":"Am J Physiol"},{"issue":"3","key":"10.1016\/j.mehy.2017.11.002_b0145","doi-asserted-by":"crossref","first-page":"161","DOI":"10.7326\/0003-4819-123-3-199508010-00001","article-title":"Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial","volume":"123","author":"Bergasa","year":"1995","journal-title":"Ann Intern Med"},{"issue":"3","key":"10.1016\/j.mehy.2017.11.002_b0150","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1053\/j.gastro.2010.05.009","article-title":"Lysophosphatidic acid is a potential mediator of cholestatic pruritus","volume":"139","author":"Kremer","year":"2012","journal-title":"Gastroenterology"},{"issue":"4","key":"10.1016\/j.mehy.2017.11.002_b0155","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/hep.25748","article-title":"Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions","volume":"56","author":"Kremer","year":"2012","journal-title":"Hepatology"},{"issue":"5","key":"10.1016\/j.mehy.2017.11.002_b0160","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1016\/j.ajpath.2014.01.029","article-title":"Potentials of the circulating pruritogenic mediator lysophosphatidic acid in development of allergic skin inflammation in mice: role of blood cell-associated lysophospholipase D activity of autotaxin","volume":"184","author":"Shimizu","year":"2014","journal-title":"Am J Pathol"},{"issue":"4797","key":"10.1016\/j.mehy.2017.11.002_b0165","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1136\/bmj.2.4797.1289","article-title":"Testosterone therapy for the pruritus of obstructive jaundice","volume":"2","author":"Lloyd-Thomas","year":"1952","journal-title":"Br Med J"},{"issue":"2","key":"10.1016\/j.mehy.2017.11.002_b0170","first-page":"121","article-title":"Bile acids and bile acid sulfates in the skin of patients with cholestasis and pruritus","volume":"12","author":"Stiehl","year":"1974","journal-title":"Z Gastroenterol"},{"issue":"5","key":"10.1016\/j.mehy.2017.11.002_b0175","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1001\/archderm.1974.01630050024005","article-title":"Pruritus induced by crude bile and purified bile acids. Experimental production of pruritus in human skin","volume":"109","author":"Varadi","year":"1974","journal-title":"Arch Dermatol"},{"issue":"6","key":"10.1016\/j.mehy.2017.11.002_b0180","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1023\/A:1018868126743","article-title":"Adjuvant cholylsarcosine during ursodeoxycholic acid treatment of primary biliary cirrhosis","volume":"43","author":"Ricci","year":"1998","journal-title":"Dig Dis Sci"},{"issue":"4","key":"10.1016\/j.mehy.2017.11.002_b0185","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1172\/JCI64551","article-title":"The TGR5 receptor mediates bile acid-induced itch and analgesia","volume":"123","author":"Alemi","year":"2013","journal-title":"J Clin Invest"},{"issue":"7","key":"10.1016\/j.mehy.2017.11.002_b0190","doi-asserted-by":"crossref","first-page":"e0129866","DOI":"10.1371\/journal.pone.0129866","article-title":"Impaired itching perception in murine models of cholestasis is supported by dysregulation of GPBAR1 signaling","volume":"10","author":"Cipriani","year":"2015","journal-title":"PLoS ONE"},{"issue":"6","key":"10.1016\/j.mehy.2017.11.002_b0195","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1053\/j.gastro.2014.08.042","article-title":"The bile acid receptor TGR5 activates the TRPA1 channel to induce itch in mice","volume":"147","author":"Lieu","year":"2014","journal-title":"Gastroenterology"},{"issue":"1\u20132","key":"10.1016\/j.mehy.2017.11.002_b0200","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1582-4934.2009.00997.x","article-title":"FXR an emerging therapeutic target for the treatment of atherosclerosis","volume":"14","author":"Mencarelli","year":"2010","journal-title":"J Cell Mol Med"},{"issue":"2","key":"10.1016\/j.mehy.2017.11.002_b0205","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1124\/jpet.104.079665","article-title":"Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis","volume":"313","author":"Fiorucci","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"10.1016\/j.mehy.2017.11.002_b0210","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1021\/jm401873d","article-title":"Design, synthesis, and biological evaluation of potent dual agonists of nuclear and membrane bile acid receptors","volume":"57","author":"D'Amore","year":"2014","journal-title":"J Med Chem"},{"issue":"7","key":"10.1016\/j.mehy.2017.11.002_b0215","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A placebo-controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","author":"Nevens","year":"2016","journal-title":"N Engl J Med"},{"issue":"9972","key":"10.1016\/j.mehy.2017.11.002_b0220","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S0140-6736(14)61933-4","article-title":"Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial","volume":"385","author":"Neuschwander-Tetri","year":"2015","journal-title":"Lancet"},{"issue":"20","key":"10.1016\/j.mehy.2017.11.002_b0225","doi-asserted-by":"crossref","first-page":"8477","DOI":"10.1021\/jm501273r","article-title":"Exploitation of cholane scaffold for the discovery of potent and selective farnesoid X receptor (FXR) and G-protein coupled bile acid receptor 1 (GP-BAR1) ligands","volume":"57","author":"Festa","year":"2014","journal-title":"J Med Chem"},{"issue":"3","key":"10.1016\/j.mehy.2017.11.002_b0230","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1097\/00000542-200003000-00023","article-title":"An experimental itch model in monkeys: characterization of intrathecal morphine-induced scratching and antinociception","volume":"92","author":"Ko","year":"2000","journal-title":"Anesthesiology"},{"issue":"1","key":"10.1016\/j.mehy.2017.11.002_b0235","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.pbb.2006.07.004","article-title":"Nalfurafine, a kappa opioid receptor agonist, inhibits scratching behavior secondary to cholestasis induced by chronic ethynylestradiol injections in rats","volume":"85","author":"Inan","year":"2006","journal-title":"Pharmacol Biochem Behav"},{"issue":"6","key":"10.1016\/j.mehy.2017.11.002_b0240","doi-asserted-by":"crossref","first-page":"e0178991","DOI":"10.1371\/journal.pone.0178991","article-title":"Long-term efficacy and safety of nalfurafine hydrochloride on pruritus in chronic liver disease patients: Patient-reported outcome based analyses","volume":"12","author":"Kamimura","year":"2017","journal-title":"PLoS ONE"},{"issue":"10","key":"10.1016\/j.mehy.2017.11.002_b0245","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1111\/hepr.12830","article-title":"Efficacy of nalfurafine hydrochloride in patients with chronic liver disease with refractory pruritus: a randomized, double-blind trial","volume":"47","author":"Kumada","year":"2017","journal-title":"Hepatol Res"},{"key":"10.1016\/j.mehy.2017.11.002_b0250","doi-asserted-by":"crossref","DOI":"10.1097\/j.pain.0000000000001043","article-title":"The discovery of endogenous opioid systems: what it has meant for the clinician's understanding of pain and its treatment","author":"Ballantyne","year":"2017","journal-title":"Pain"}],"container-title":["Medical Hypotheses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030698771731112X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030698771731112X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,10,5]],"date-time":"2019-10-05T14:14:41Z","timestamp":1570284881000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S030698771731112X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":50,"alternative-id":["S030698771731112X"],"URL":"https:\/\/doi.org\/10.1016\/j.mehy.2017.11.002","relation":{},"ISSN":["0306-9877"],"issn-type":[{"value":"0306-9877","type":"print"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The pruritus of cholestasis: From bile acids to opiate agonists: Relevant after all these years","name":"articletitle","label":"Article Title"},{"value":"Medical Hypotheses","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mehy.2017.11.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}