{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:37:19Z","timestamp":1753879039058,"version":"3.41.2"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["LUTS"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of this study was to investigate the mechanism of TRPM8 in neuroproliferation and pain, as well as the relevance of the Akt\/mTOR signaling pathway in mice with IC\/BPS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The model of IC\/BPS was established in wild and TRPM8<jats:sup>\u2212\/\u2212<\/jats:sup> mice. The mechanical sensitivity was measured. The number of neurite segments, length of neurites, and density of neurites were all counted. IL\u20106 and norepinephrine levels were detected by ELISA, Western blot was used to detect protein levels of TRPM8, Akt, p\u2010Akt, mTOR, p\u2010mTOR. Immunofluorescence was used to detect TRPM8 expression and distribution in neurites, neurons, and sensory nerves in mouse bladder tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pain threshold in the IC\/BPS group was decreased, and neurite segments, length, and density were all significantly enhanced when compared to the control group. The parameters in the IC\/BPS model\u2009+\u2009Menthol group were more statistically significant. Neurite number and density were lower in TRPM8 knockout\u2010model mice than in IC\/BPS model mice. The expression of TRPM8 and the ratios of p\u2010Akt\/Akt and p\u2010mTOR\/mTOR rose in the IC\/BPS model group. In TRPM8 knockout\u2010model mice, the ratios of p\u2010Akt\/Akt and p\u2010mTOR\/mTOR were not substantially different from those in the control group. TRPM8 knockout\u2010model mice had considerably lower levels of serum IL\u20106 and urine norepinephrine than IC\/BPS model mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TRPM8 can induce pain hypersensitivity and sensory nerve proliferation by activating Akt\/mTOR pathway and raising the expression of IL\u20106 and norepinephrine in IC\/BPS models. These findings offer new perspectives on IC\/BPS treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/luts.12537","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T01:10:23Z","timestamp":1731373823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transient Receptor Potential Melastatin 8 Contributes to Cystitis\u2010Induced Neuronal Sprouting and Pain Hypersensitivity Through <scp>AKT<\/scp>\/<scp>mTOR<\/scp> Signaling Pathway in Interstitial Cystitis\/Bladder Pain Syndrome"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3404-7232","authenticated-orcid":false,"given":"Liyang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Urology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-2268","authenticated-orcid":false,"given":"Ran","family":"Chang","sequence":"additional","affiliation":[{"name":"Urologic Rehabilitation Department Beijing Boai Hospital, China Rehabilitation Research Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9004-8144","authenticated-orcid":false,"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.01.086"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.13985"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0891\u20100618(00)00115\u20100"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2016.13"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2020.09.037"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature719"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aen107"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.12.030189.001015"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072067"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.529552"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90269.2008"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102490\u20106\u20106"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5004"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00478"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010420170\u20105.00005\u20102"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2017.04.005"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2139\u201010.2011"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp\u20102019\u20100156"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.01.027"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102982.2002.00353.x"}],"container-title":["LUTS: Lower Urinary Tract Symptoms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/luts.12537","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T01:28:23Z","timestamp":1732670903000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/luts.12537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/luts.12537"],"URL":"https:\/\/doi.org\/10.1111\/luts.12537","archive":["Portico"],"relation":{},"ISSN":["1757-5664","1757-5672"],"issn-type":[{"type":"print","value":"1757-5664"},{"type":"electronic","value":"1757-5672"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12537"}}