{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:24:38Z","timestamp":1761765878328},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,1,11]],"date-time":"2015-01-11T00:00:00Z","timestamp":1420934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["LUTS"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the effect of descending serotonergic and noradrenergic pathways on nociception in the lower urinary tract (<jats:styled-content style=\"fixed-case\">LUT<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prague\u2013<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>awley rats were used. Following intraperitoneal administration of <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>ehicle or <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>ilnacipran (30\u2009mg\/kg), which is one of serotonin\u2010noradrenaline reuptake inhibitors (<jats:styled-content style=\"fixed-case\">SNRI<\/jats:styled-content>), 0.1% <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content> was infused into the bladder in normal (<jats:italic>n\u2009=<\/jats:italic>\u20094, each) and spinal cord injury (<jats:styled-content style=\"fixed-case\">SCI<\/jats:styled-content>) (<jats:italic>n\u2009=<\/jats:italic>\u20094, each) rats for 2\u2009h on consciousness, and c\u2010<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>os, 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">D\u03b2H<\/jats:styled-content> were stained using immunohistochemistry at the <jats:styled-content style=\"fixed-case\">L6<\/jats:styled-content> spinal cord as spinal areas associated with <jats:styled-content style=\"fixed-case\">LUT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In <jats:styled-content style=\"fixed-case\">SCI<\/jats:styled-content> rats, 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">D\u03b2H<\/jats:styled-content>\u2010positive fibers were not observed at the <jats:styled-content style=\"fixed-case\">L6<\/jats:styled-content> spinal cord, while there were many 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">D\u03b2H<\/jats:styled-content>\u2010positive fibers in normal rats. The total number of c\u2010<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>os\u2010positive cells was significantly increased in <jats:styled-content style=\"fixed-case\">SCI<\/jats:styled-content> rats compared to <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>ormal rats (209.4\u2009\u00b1\u20097.1 in <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>ormal, 336.4\u2009\u00b1\u200928.9 in <jats:styled-content style=\"fixed-case\">SCI<\/jats:styled-content>, <jats:italic>P &lt;<\/jats:italic> 0.05), which indicated that interruption of supraspinal modulation enhances nocieptive transmission in the <jats:styled-content style=\"fixed-case\">LUT<\/jats:styled-content>. Regarding the effect of <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>ilnacipran administration, the number of c\u2010<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>os\u2010positive cells was significantly decreased at all region of the <jats:styled-content style=\"fixed-case\">L6<\/jats:styled-content> spinal cord in normal rats (<jats:italic>P &lt;<\/jats:italic> 0.05), while this reduction was not observed in <jats:styled-content style=\"fixed-case\">SCI<\/jats:styled-content> rats. This result demonstrated that administration of <jats:styled-content style=\"fixed-case\">SNRI<\/jats:styled-content> attenuates nocieptive transmission in the <jats:styled-content style=\"fixed-case\">LUT<\/jats:styled-content>, indicating that 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content> and noradrenaline work as mediators of endogenous analgesic mechanisms through the supraspinal descending pain pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Supraspinal projections of descending serotonergic and noradrenergic pathways to the lower lumbar spinal cord modulate nocieptive transmission in the <jats:styled-content style=\"fixed-case\">LUT<\/jats:styled-content>. Administration of <jats:styled-content style=\"fixed-case\">SNRI<\/jats:styled-content> attenuates nocieptive transmission in the <jats:styled-content style=\"fixed-case\">LUT<\/jats:styled-content>, which could result from enhancement of modulating descending serotonergic and noradrenergic pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/luts.12085","type":"journal-article","created":{"date-parts":[[2015,1,12]],"date-time":"2015-01-12T04:15:58Z","timestamp":1421036158000},"page":"186-190","source":"Crossref","is-referenced-by-count":4,"title":["Supraspinal Projection of Serotonergic and Noradrenergic Pathways Modulates Nociceptive Transmission in the Lower Urinary Tract of Rats"],"prefix":"10.1111","volume":"8","author":[{"given":"Takahiko","family":"MITSUI","sequence":"first","affiliation":[{"name":"Department of Urology Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"KANNO","sequence":"additional","affiliation":[{"name":"Department of Urology Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeya","family":"KITTA","sequence":"additional","affiliation":[{"name":"Department of Urology Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimihiko","family":"MORIYA","sequence":"additional","affiliation":[{"name":"Department of Urology Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuya","family":"NONOMURA","sequence":"additional","affiliation":[{"name":"Department of Urology Hokkaido University Graduate School of Medicine  Sapporo 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