{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:16:27Z","timestamp":1784574987441,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Opioids are indicated for pain that occurs with cancer and other disorders that become more prevalent with aging. The most prevalent and persistent adverse effect of opioid therapy is opioid\u2010induced constipation (OIC). OIC impairs patient quality of life (QoL) and leads to suboptimal pain management due to medication non\u2010adherence. Unlike other adverse effects, OIC persists and is not associated with pharmacological tolerance, necessitating long\u2010term management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The objective of this study is to evaluate current clinical strategies for OIC by comparing recommendations from American, European, and Japanese clinical guidelines. We reviewed the clinical evidence for the peripherally acting \u03bc\u2010opioid receptor antagonist (PAMORA) naldemedine (the only PAMORA approved in Japan) and the rationale for early intervention in OIC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The clinical guidelines and recent clinical trial data, including the COMPOSE program (phase III clinical trials of naldemedine for OIC in patients with chronic non\u2010cancer pain), were reviewed to establish an evidence\u2010based framework for the management of chronic cancer and non\u2010cancer pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Conventional laxatives frequently provide inadequate relief as they address secondary symptoms rather than the underlying receptor\u2010mediated cause. PAMORAs (including naldemedine, methyl naltrexone, and naloxegol) antagonize gastrointestinal opioid receptors without compromising central analgesia. Early initiation of PAMORAs stabilizes bowel function and reduces the incidence of treatment\u2010related diarrhea that occurs when using conventional laxatives to treat OIC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The 2023 Japanese guidelines advocate the proactive use of the PAMORA naldemedine as a primary treatment option. This mechanism\u2010based early intervention model offers a promising framework for optimizing QoL and implementing effective analgesia in an aging global population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70343","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:56:29Z","timestamp":1778136989000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Current Strategies and Future Perspectives in the Management of Opioid\u2010Induced Constipation: A Review of International and Japanese Guidelines"],"prefix":"10.1111","volume":"38","author":[{"given":"Noriaki","family":"Manabe","sequence":"first","affiliation":[{"name":"Division of Endoscopy and Ultrasonography, Department of Clinical Laboratory Medicine Kawasaki Medical School  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eikichi","family":"Ihara","sequence":"additional","affiliation":[{"name":"Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinomi","family":"Yomiya","sequence":"additional","affiliation":[{"name":"Department of Palliative Care Hiroshima City Hiroshima Citizens Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Iseki","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine Juntendo University Faculty of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Torii","sequence":"additional","affiliation":[{"name":"Torii Medical Clinic  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Miwa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Kawanishi City Medical Hospital  Kawanishi City Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-7514","authenticated-orcid":false,"given":"Michael","family":"Camilleri","sequence":"additional","affiliation":[{"name":"C.E.N.T.E.R. Program, Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/papr.12445"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13762"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.07.016"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S282738"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(18)30008-6"},{"key":"e_1_2_16_7_1","first-page":"1858","article-title":"Opioid\u2010Induced Constipation: An International Survey in Patients With Chronic Noncancer Pain","volume":"112","author":"Mueller\u2010Lissner S.","year":"2017","journal-title":"American Journal of Gastroenterology"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12443"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.186320"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176333"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0897190017732263"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2020-101403"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-020-00902-w"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.693"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(17)30105-X"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001174"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15791"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.01.021"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/papr.12535"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00540-025-03559-x"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310246"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13762"},{"key":"e_1_2_16_23_1","first-page":"62","article-title":"Evidence\u2010Based Clinical Guidelines for Chronic Constipation 2023","volume":"106","author":"Ihara E.","year":"2025","journal-title":"Digestion"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.0853"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.106"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-316001"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.0044"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy148"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70040-2"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/jpm.2021.0438"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-020-1173-z"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0278823"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-019-05016-4"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00540-025-03559-x"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707377"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12437"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003448.pub4"},{"key":"e_1_2_16_38_1","unstructured":"Ministry of Health Labour and Welfare Summary report of the comprehensive survey of living conditions 2022accessed at https:\/\/www.mhlw.go.jp\/toukei\/saikin\/hw\/k\u2010tyosa\/k\u2010tyosa22\/dl\/04.pdf."},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050640618786145"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics15040476"}],"container-title":["Neurogastroenterology &amp; 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