{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:12:56Z","timestamp":1790035976280,"version":"4.0.1"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:00:00Z","timestamp":1608336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K15792"],"award-info":[{"award-number":["17K15792"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although interstitial cystitis\/bladder pain syndrome (IC\/BPS) is a chronic condition causing bladder pain and urinary symptoms, effective treatments have not been established. The aim of this study was to adapt a chronic cystitis model in rats using lipopolysaccharide (LPS), which reflects IC\/BPS pathology, and characterize the model's histological and behavioral effects. Furthermore, we investigated the effect of an \u03b1<jats:sub>2<\/jats:sub>\u03b4 subunit ligand, gabapentin (GBP), on bladder hypersensitivity of rats with chronic cystitis. Cystitis models were created by repeated intravesical injections of LPS. In the histological examination, the LPS\u2010injected group had greater inflammatory response, fibrosis, and abnormally thick re\u2010epithelialization. In the LPS\u2010injected group, LPS prompted hyperalgesia in both the lower abdomen and hind paw regions after day 1 of the first injection compared with the saline\u2010injected controls, without any recovery for 21\u00a0days at least. During cystometry, the LPS\u2010injected group showed bladder hyperactivity at all times. Systemic administration of GBP reduced cystitis\u2010related pain due to chronic inflammation and reduced the increased frequency of voiding in the LPS\u2010injected group. These results suggest that repeated intravesical injections of LPS induce long\u2010lasting bladder inflammation, pain, and overactivity in rats, while GBP is effective in the management of those symptoms in this chronic cystitis model. The current study identifies a relatively simple method to develop an animal model for chronic cystitis and provides evidence that GBP may be an effective treatment option for patients with IC\/BPS.<\/jats:p>","DOI":"10.1002\/prp2.697","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T12:04:35Z","timestamp":1608379475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Gabapentin reduces painful bladder hypersensitivity in rats with lipopolysaccharide\u2010induced chronic cystitis"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-2602","authenticated-orcid":false,"given":"Masaru","family":"Yoshizumi","sequence":"first","affiliation":[{"name":"Department of Physiology and Anatomy Faculty of Pharmaceutical Sciences Tohoku Medical and Pharmaceutical University Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chizuko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Physiology and Anatomy Faculty of Pharmaceutical Sciences Tohoku Medical and Pharmaceutical University Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Anatomy Faculty of Pharmaceutical Sciences Tohoku Medical and Pharmaceutical University Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2003.10.034"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.01.086"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2006.11.084"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.03.132"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1973.tb12230.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(79)90222-3"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)66406-1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/eujp.1998.0105"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67495-2"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.2001.02138.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.09.026"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135414"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61159-5"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000456077"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24833-x"},{"key":"e_1_2_10_17_1","first-page":"1026","article-title":"Gabapentin suppresses ectopic nerve discharges and reverses allodynia in neuropathic rats","volume":"288","author":"Pan HL","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.041574"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706109"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.04.022"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200703000-00021"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.10.5768"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05212.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318254e6fd"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2011.10.022"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00540-009-0774-z"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.5213\/inj.2013.17.2.78"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-018-2021-8"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2490-9-16"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00553.2009"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14749"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960624)370:2<191::AID-CNE5>3.0.CO;2-Y"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00139.2013"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003898"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01305"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00043.2014"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.5213\/inj.1734898.449"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2007.12.091"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44631-3"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3023-06.2006"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2012.03217.x"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22721"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-013-0057-y"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.05.012"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-06-01868.2001"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.205"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.10.027"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31818dac9c"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.12.015"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.01.040"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1925.sp000345"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(78)90092-7"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63247-0.00015-8"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-03-00585.1991"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.073"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24215"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0204-3"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903630306"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00482-9"},{"key":"e_1_2_10_62_1","first-page":"163","article-title":"Activation of the locus coeruleus noradrenergic system by intracoerulear microinfusion of corticotropin\u2010releasing factor: effects on discharge rate, cortical norepinephrine levels and cortical electroencephalographic activity","volume":"281","author":"Curtis AL","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.91013.2008"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2017.09.020"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08250.x"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.07.009"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.10.015"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.697","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.697","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.697","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T00:28:32Z","timestamp":1693700912000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,19]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1002\/prp2.697"],"URL":"https:\/\/doi.org\/10.1002\/prp2.697","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,19]]},"assertion":[{"value":"2020-10-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00697"}}