{"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":1790035976069,"version":"4.0.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s00210-025-04503-2","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T08:24:02Z","timestamp":1754555042000},"page":"1287-1295","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intravesical substance P enhances bladder afferent nerve activity without the influence of the micturition reflex"],"prefix":"10.1007","volume":"399","author":[{"given":"Hiroki","family":"Natsuya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoe","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Aizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"4503_CR1","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jphs.2023.04.005","volume":"152","author":"N Aizawa","year":"2023","unstructured":"Aizawa N, Fujita T (2023) Comparison of the effects of two anesthetics, isoflurane and urethane, on bladder function in rats. J Pharmacol Sci 152:144\u2013150. https:\/\/doi.org\/10.1016\/j.jphs.2023.04.005","journal-title":"J Pharmacol Sci"},{"key":"4503_CR2","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/nau.20940","volume":"30","author":"N Aizawa","year":"2011","unstructured":"Aizawa N, Igawa Y, Andersson KE, Iijima K, Nishizawa O, Wyndaele JJ (2011) Effects of intravesical instillation of ATP on rat bladder primary afferent activity and its relationship with capsaicin-sensitivity. Neurourol Urodyn 30:163\u2013168. https:\/\/doi.org\/10.1002\/nau.20940","journal-title":"Neurourol Urodyn"},{"issue":"1","key":"4503_CR3","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/nau.21212","volume":"31","author":"N Aizawa","year":"2012","unstructured":"Aizawa N, Wyndaele JJ, Homma Y, Igawa Y (2012) Effects of TRPV4 cation channel activation on the primary bladder afferent activities of the rat. Neurourol Urodyn 31(1):148\u2013155. https:\/\/doi.org\/10.1002\/nau.21212","journal-title":"Neurourol Urodyn"},{"key":"4503_CR4","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/j.juro.2014.04.008","volume":"192","author":"N Aizawa","year":"2014","unstructured":"Aizawa N, Hedlund P, Fullhase C, Ito H, Homma Y, Igawa Y (2014) Inhibition of peripheral FAAH depresses activities of bladder mechanosensitive nerve fibers of the rat. J Urol 192:956\u2013963. https:\/\/doi.org\/10.1016\/j.juro.2014.04.008","journal-title":"J Urol"},{"key":"4503_CR5","doi-asserted-by":"publisher","DOI":"10.1111\/luts.12538","volume":"16","author":"N Aizawa","year":"2024","unstructured":"Aizawa N, Natsuya H, Fujita T (2024) Changes of the Urothelial Barrier System in the Cyclophosphamide-Induced Cystitis in Rats by Using a Newly Established \u201cInside-Out\u201d Urinary Bladder Preparation. LUTS: Lower Urinary Tract Symptoms 16:e12538. https:\/\/doi.org\/10.1111\/luts.12538","journal-title":"LUTS: Lower Urinary Tract Symptoms"},{"key":"4503_CR6","doi-asserted-by":"publisher","first-page":"F840","DOI":"10.1152\/ajprenal.00187.2002","volume":"284","author":"CT Chien","year":"2003","unstructured":"Chien CT, Yu HJ, Lin TB, Lai MK, Hsu SM (2003) Substance P via NK1 receptor facilitates hyperactive bladder afferent signaling via action of ROS. Am J Physiol Renal Physiol 284:F840-851. https:\/\/doi.org\/10.1152\/ajprenal.00187.2002","journal-title":"Am J Physiol Renal Physiol"},{"key":"4503_CR7","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/s0090-4295(02)01544-3","volume":"59","author":"CJ Fowler","year":"2002","unstructured":"Fowler CJ (2002) Bladder afferents and their role in the overactive bladder. Urology 59:37\u201342. https:\/\/doi.org\/10.1016\/s0090-4295(02)01544-3","journal-title":"Urology"},{"key":"4503_CR8","doi-asserted-by":"publisher","first-page":"2535","DOI":"10.1016\/j.juro.2006.08.018","volume":"176","author":"SA Green","year":"2006","unstructured":"Green SA, Alon A, Ianus J, McNaughton KS, Tozzi CA, Reiss TF (2006) Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence. J Urol 176:2535\u20132540. https:\/\/doi.org\/10.1016\/j.juro.2006.08.018","journal-title":"J Urol"},{"key":"4503_CR9","doi-asserted-by":"publisher","first-page":"F1174","DOI":"10.1152\/ajprenal.00106.2018","volume":"315","author":"L Grundy","year":"2018","unstructured":"Grundy L, Chess-Williams R, Brierley SM, Mills K, Moore KH, Mansfield K, Rose\u2019Meyer R, Sellers D, Grundy D (2018) NKA enhances bladder-afferent mechanosensitivity via urothelial and detrusor activation. Am J Physiol Renal Physiol 315:F1174\u2013F1185. https:\/\/doi.org\/10.1152\/ajprenal.00106.2018","journal-title":"Am J Physiol Renal Physiol"},{"key":"4503_CR10","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.regpep.2011.02.004","volume":"167","author":"YJ Heng","year":"2011","unstructured":"Heng YJ, Saunders CI, Kunde DA, Geraghty DP (2011) TRPV1, NK1 receptor and substance P immunoreactivity and gene expression in the rat lumbosacral spinal cord and urinary bladder after systemic, low dose vanilloid administration. Regul Pept 167:250\u2013258. https:\/\/doi.org\/10.1016\/j.regpep.2011.02.004","journal-title":"Regul Pept"},{"key":"4503_CR11","doi-asserted-by":"publisher","first-page":"49","DOI":"10.2220\/biomedres.27.49","volume":"27","author":"M Ikeda","year":"2006","unstructured":"Ikeda M, Kawatani M, Maruyama T, Ishihama H (2006) Prostaglandin facilitates afferent nerve activity via EP1 receptors during urinary bladder inflammation in rats. Biomed Res 27:49\u201354. https:\/\/doi.org\/10.2220\/biomedres.27.49","journal-title":"Biomed Res"},{"key":"4503_CR12","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S0022-5347(01)67290-2","volume":"154","author":"O Ishizuka","year":"1995","unstructured":"Ishizuka O, Mattiasson A, Andersson KE (1995) Tachykinin effects on bladder activity in conscious normal rats. J Urol 154:257\u2013261. https:\/\/doi.org\/10.1016\/S0022-5347(01)67290-2","journal-title":"J Urol"},{"key":"4503_CR13","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/j.1757-5672.2010.00085.x","volume":"3","author":"T Ito","year":"2011","unstructured":"Ito T, Ishikawa T, Matsumoto-Miyai K, Kawatani M (2011) Pulse diode laser irradiation (830 nm) of lumbosacral spinal roots diminished hyperreflexia-induced by acetic acid or prostaglandin E2 infusion in rat urinary bladder. Low Urin Tract Symptoms 3:69\u201375. https:\/\/doi.org\/10.1111\/j.1757-5672.2010.00085.x","journal-title":"Low Urin Tract Symptoms"},{"key":"4503_CR14","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1038\/252734a0","volume":"252","author":"S Konishi","year":"1974","unstructured":"Konishi S, Otsuka M (1974) Excitatory action of hypothalamic substance P on spinal motoneurones of newborn rats. Nature 252:734\u2013735. https:\/\/doi.org\/10.1038\/252734a0","journal-title":"Nature"},{"key":"4503_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0167-0115(01)00285-3","volume":"101","author":"A Lecci","year":"2001","unstructured":"Lecci A, Maggi CA (2001) Tachykinins as modulators of the micturition reflex in the central and peripheral nervous system. Regul Pept 101:1\u201318. https:\/\/doi.org\/10.1016\/s0167-0115(01)00285-3","journal-title":"Regul Pept"},{"key":"4503_CR16","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1007\/s10753-018-0888-2","volume":"42","author":"BK Liu","year":"2019","unstructured":"Liu BK, Jin XW, Lu HZ, Zhang X, Zhao ZH, Shao Y (2019) The effects of neurokinin-1 receptor antagonist in an experimental autoimmune cystitis model resembling bladder pain syndrome\/interstitial cystitis. Inflammation 42:246\u2013254. https:\/\/doi.org\/10.1007\/s10753-018-0888-2","journal-title":"Inflammation"},{"key":"4503_CR17","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/0306-3623(94)00292-u","volume":"26","author":"CA Maggi","year":"1995","unstructured":"Maggi CA (1995) The mammalian tachykinin receptors. Gen Pharmacol 26:911\u2013944. https:\/\/doi.org\/10.1016\/0306-3623(94)00292-u","journal-title":"Gen Pharmacol"},{"key":"4503_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0006-8993(87)90263-0","volume":"415","author":"CA Maggi","year":"1987","unstructured":"Maggi CA, Santicioli P, Geppetti P, Furio M, Frilli S, Conte B, Fanciullacci M, Giuliani S, Meli A (1987) The contribution of capsaicin-sensitive innervation to activation of the spinal vesico-vesical reflex in rats: relationship between substance P levels in the urinary bladder and the sensory-efferent function of capsaicin-sensitive sensory neurons. Brain Res 415:1\u201313. https:\/\/doi.org\/10.1016\/0006-8993(87)90263-0","journal-title":"Brain Res"},{"key":"4503_CR19","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1111\/j.1476-5381.1991.tb09823.x","volume":"103","author":"CA Maggi","year":"1991","unstructured":"Maggi CA, Patacchini R, Santicioli P, Giuliani S (1991) Tachykinin antagonists and capsaicin-induced contraction of the rat isolated urinary bladder: evidence for tachykinin-mediated cotransmission. Br J Pharmacol 103:1535\u20131541. https:\/\/doi.org\/10.1111\/j.1476-5381.1991.tb09823.x","journal-title":"Br J Pharmacol"},{"key":"4503_CR20","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1080\/003655999750042187","volume":"201","author":"J Morrison","year":"1999","unstructured":"Morrison J, Wen J, Kibble A (1999) Activation of pelvic afferent nerves from the rat bladder during filling. Scand J Urol Nephrol Suppl 201:73\u201375. https:\/\/doi.org\/10.1080\/003655999750042187","journal-title":"Scand J Urol Nephrol Suppl"},{"key":"4503_CR21","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1471-2490-10-10","volume":"10","author":"A Munoz","year":"2010","unstructured":"Munoz A, Gangitano DA, Smith CP, Boone TB, Somogyi GT (2010) Removal of urothelium affects bladder contractility and release of ATP but not release of NO in rat urinary bladder. BMC Urol 10:10. https:\/\/doi.org\/10.1186\/1471-2490-10-10","journal-title":"BMC Urol"},{"key":"4503_CR22","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/0006-8993(89)90742-7","volume":"480","author":"JI Pascual","year":"1989","unstructured":"Pascual JI, Insausti R, Gonzalo LM (1989) The pelvic innervation in the rat: different spinal origin and projections in Sprague-Dawley and Wistar rats. Brain Res 480:397\u2013402","journal-title":"Brain Res"},{"key":"4503_CR23","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1152\/physrev.00031.2013","volume":"94","author":"MS Steinhoff","year":"2014","unstructured":"Steinhoff MS, von Mentzer B, Geppetti P, Pothoulakis C, Bunnett NW (2014) Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev 94:265\u2013301. https:\/\/doi.org\/10.1152\/physrev.00031.2013","journal-title":"Physiol Rev"},{"key":"4503_CR24","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1213\/01.ane.0000099362.01312.3a","volume":"98","author":"A Sukiennik","year":"2004","unstructured":"Sukiennik A, Carr DB, Bonney I, Marchand JE, Wurm H, Sant GR (2004) The effect of short-term epidural local anesthetic blockade on urinary levels of substance P in interstitial cystitis. Anesth Analg 98:846\u2013850. https:\/\/doi.org\/10.1213\/01.ane.0000099362.01312.3a. (table of contents)","journal-title":"Anesth Analg"},{"key":"4503_CR25","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.neuropharm.2018.01.037","volume":"133","author":"M Tsubota","year":"2018","unstructured":"Tsubota M, Okawa Y, Irie Y, Maeda M, Ozaki T, Sekiguchi F, Ishikura H, Kawabata A (2018) Involvement of the cystathionine-gamma-lyase\/Ca(v)3.2 pathway in substance P-induced bladder pain in the mouse, a model for nonulcerative bladder pain syndrome. Neuropharmacology 133:254\u2013263. https:\/\/doi.org\/10.1016\/j.neuropharm.2018.01.037","journal-title":"Neuropharmacology"},{"key":"4503_CR26","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/s41585-021-00428-6","volume":"18","author":"M Vanneste","year":"2021","unstructured":"Vanneste M, Segal A, Voets T, Everaerts W (2021) Transient receptor potential channels in sensory mechanisms of the lower urinary tract. Nat Rev Urol 18:139\u2013159. https:\/\/doi.org\/10.1038\/s41585-021-00428-6","journal-title":"Nat Rev Urol"},{"key":"4503_CR27","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/s0090-4295(01)01639-9","volume":"59","author":"N Yoshimura","year":"2002","unstructured":"Yoshimura N, Seki S, Chancellor MB, de Groat WC, Ueda T (2002) Targeting afferent hyperexcitability for therapy of the painful bladder syndrome. Urology 59:61\u201367. https:\/\/doi.org\/10.1016\/s0090-4295(01)01639-9","journal-title":"Urology"},{"key":"4503_CR28","doi-asserted-by":"publisher","first-page":"12067","DOI":"10.1523\/JNEUROSCI.0496-07.2007","volume":"27","author":"H Zhang","year":"2007","unstructured":"Zhang H, Cang CL, Kawasaki Y, Liang LL, Zhang YQ, Ji RR, Zhao ZQ (2007) Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia. J Neurosci 27:12067\u201312077. https:\/\/doi.org\/10.1523\/JNEUROSCI.0496-07.2007","journal-title":"J Neurosci"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04503-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-04503-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04503-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T22:06:51Z","timestamp":1771538811000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-04503-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["4503"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-04503-2","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,7]]},"assertion":[{"value":"26 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The experimental protocol was approved by the Institutional Animal Care and Use Committee of Dokkyo Medical University (No. 1488).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}