{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:36:53Z","timestamp":1792517813437,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004765","name":"Honeywell Hometown Solutions","doi-asserted-by":"publisher","award":["U54 DK112079"],"award-info":[{"award-number":["U54 DK112079"]}],"id":[{"id":"10.13039\/100004765","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 DK112079"],"award-info":[{"award-number":["U54 DK112079"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U54 DK112079"],"award-info":[{"award-number":["U54 DK112079"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>There is clinical evidence showing that prostatic inflammation contributes to overactive bladder symptoms in male patients; however, little is known about the underlying mechanisms<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In this study, we investigated the mechanism that prostatic inflammation causes detrusor overactivity by using a rat model of chemically induced prostatic inflammation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We observed a significant number of dorsal root ganglion neurons with dichotomized afferents innervating both prostate and bladder.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We also found that prostatic inflammation induces bladder overactivity and urothelial NGF overexpression in the bladder, both dependent on activation of the pelvic nerve, as well as changes in ion channel expression and hyperexcitability of bladder afferent neurons.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These results indicate that the prostate\u2010to\u2010bladder cross\u2010sensitization through primary afferent pathways in the pelvic nerve, which contain dichotomized afferents, could be an important mechanism contributing to bladder overactivity and afferent hyperexcitability induced by prostatic inflammation.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Prostatic inflammation is reportedly an important factor inducing lower urinary tract symptoms (LUTS) including urinary frequency, urgency and incontinence in patients with benign prostatic hyperplasia (BPH). However, the underlying mechanisms inducing bladder dysfunction after prostatic inflammation are not well clarified. We therefore investigated the effects of prostatic inflammation on bladder activity and afferent function using a rat model of non\u2010bacterial prostatic inflammation. We demonstrated that bladder overactivity, evident as decreased voided volume and shorter intercontraction intervals in cystometry, was observed in rats with prostatic inflammation\n                      <jats:italic>versus<\/jats:italic>\n                      controls. Tissue inflammation, evident as increased myeloperoxidase activity, and IL\u20101\u03b1, IL\u20101\u03b2, and IL\u20106 levels inside the prostate, but not in the bladder, following intraprostatic formalin injection induced an increase in NGF expression in the bladder urothelium, which depended on activation of the pelvic nerve. A significant proportion (18\u201319%) of dorsal root ganglion neurons were double labelled by dye tracers injected into either bladder or prostate. In rats with prostatic inflammation, TRPV1, TRPA1 and P2X2 increased, and Kv1.4, a potassium channel \u03b1\u2010subunit that can form A\u2010type potassium (K\n                      <jats:sub>A<\/jats:sub>\n                      ) channels, decreased at mRNA levels in bladder afferent and double\u2010labelled neurons\n                      <jats:italic>vs<\/jats:italic>\n                      . non\u2010labelled neurons, and slow K\n                      <jats:sub>A<\/jats:sub>\n                      current density decreased in association with hyperexcitability of these neurons. Collectively, non\u2010bacterial inflammation localized in the prostate induces bladder overactivity and enhances bladder afferent function. Thus, prostate\u2010to\u2010bladder afferent cross\u2010sensitization through primary afferents in the pelvic nerve, which contain dichotomized afferents, could underlie storage LUTS in symptomatic BPH with prostatic inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp277452","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T12:10:44Z","timestamp":1548245444000},"page":"2063-2078","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Bladder overactivity and afferent hyperexcitability induced by prostate\u2010to\u2010bladder cross\u2010sensitization in rats with prostatic inflammation"],"prefix":"10.1113","volume":"597","author":[{"given":"Yasuhito","family":"Funahashi","sequence":"first","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"},{"name":"Department of Urology Nagoya University Graduate School of Medicine  Aichi 466\u20138550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"},{"name":"Department of Urology Kyusyu University Graduate School of Medicine  Fukuoka 812\u20138582 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichiro","family":"Takaoka","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshu","family":"Ni","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald B.","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"de Groat","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6586-4545","authenticated-orcid":false,"given":"Pradeep","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-1664","authenticated-orcid":false,"given":"Naoki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"},{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2012.11137.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.07.087"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2009.07.006"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2010.04.002"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.09.023"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.4111\/kju.2012.53.2.109"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5239-04.2005"},{"key":"e_1_2_5_9_1","first-page":"327","article-title":"Neural control of the lower urinary tract","volume":"5","author":"Groat WC","year":"2015","journal-title":"Compr Physiol"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2009.00972.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-010-0528-4"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22668"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00272.2017"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.91054.2008"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-015-0082-3"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.12.090"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.21144"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.04.049"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116827"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23170"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.12.026"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2011.04.076"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2007.07389.x"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.07.053"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23320"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2007.11.026"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21034"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2012.178"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21027"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06702.x"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2016.03.077"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.106153"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2009.07.003"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.07.058"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2017.02.590"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3023-06.2006"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.269bh.x"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-11-04644.1999"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00376-X"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00243-4"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP277452","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP277452","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP277452","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP277452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T22:00:57Z","timestamp":1694037657000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP277452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,12]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1113\/JP277452"],"URL":"https:\/\/doi.org\/10.1113\/jp277452","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734903459.793556357","asserted-by":"object"}]},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,12]]},"assertion":[{"value":"2018-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}