{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T11:58:36Z","timestamp":1783857516370,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004001","name":"Guizhou Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["ZK [2022]\u4e00\u822c 359"],"award-info":[{"award-number":["ZK [2022]\u4e00\u822c 359"]}],"id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Chronic prostatitis\/chronic pelvic pain syndrome (CPPS\/CP) is a prevalent urinary disorder primarily characterized by pelvic pain and discomfort, bladder dysfunction, and sexual dysfunction. Currently, there is no effective method to alleviate the pain and lower urinary tract symptoms associated with chronic prostatitis. Resiniferatoxin (RTX), a highly potent TRPV1 receptor agonist, functions as a molecular analgesic by desensitizing TRPV1-expressing nerves. While RTX has demonstrated significant efficacy in treating various conditions, research on its application for prostatitis remains lacking. Consequently, we established a prostatitis model to investigate whether RTX could alleviate the symptoms associated with this condition. Our observations indicated that both low-dose (200\u00a0\u03bcg\/kg) and high-dose (300\u00a0\u03bcg\/kg) RTX effectively relieved pain and lower urinary tract symptoms caused by prostatitis. We noted that RTX reduced the expression of central pain-inducing substance P by reducing TRPV1 expression in the dorsal root ganglia (DRG), thereby mitigating pain. RTX also desensitizes bladder nerves by reducing TRPV1 expression in the bladder, which helps alleviate lower urinary tract symptoms caused by prostatitis. Collectively, these findings suggest that RTX may serve as a viable treatment option for alleviating prostatitis-induced pain and lower urinary tract symptoms through neural desensitization, presenting a promising therapeutic avenue for patients with prostatitis.<\/jats:p>","DOI":"10.3389\/fphar.2025.1541684","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T06:54:21Z","timestamp":1740466461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting TRPV1 channels in desensitized neural afferent pathways may help mitigate pain and lower urinary tract symptoms caused by prostatitis"],"prefix":"10.3389","volume":"16","author":[{"given":"ZhiPeng","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AnGuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiKe","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DeCan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KaiHua","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZongMin","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyu","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoChuan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ShangJun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ChaoYong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1002\/med.21427","article-title":"Medicinal chemistry, pharmacology, and clinical implications of TRPV1 receptor antagonists","volume":"37","author":"Aghazadeh Tabrizi","year":"2017","journal-title":"Med. Res. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1002\/pros.24101","article-title":"Prostate\u2010to\u2010bladder cross\u2010sensitization in a model of zymosan\u2010induced chronic pelvic pain syndrome in rats","volume":"81","author":"Aydogdu","year":"2021","journal-title":"Prostate"},{"key":"B3","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/978-3-642-54215-2_9","article-title":"TRPV1","volume":"222","author":"Bevan","year":"2014","journal-title":"Handb. Exp. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/ph9030047","article-title":"Resiniferatoxin: the evolution of the \u201cmolecular scalpel\u201d for chronic pain relief","volume":"9","author":"Brown","year":"2016","journal-title":"Pharmaceuticals"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1113\/JP277452","article-title":"Bladder overactivity and afferent hyperexcitability induced by prostate\u2010to\u2010bladder cross\u2010sensitization in rats with prostatic inflammation","volume":"597","author":"Funahashi","year":"2019","journal-title":"J. Physiology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1111\/j.1464-410X.2008.07752.x","article-title":"Regional differences in sensory innervation and suburothelial interstitial cells in the bladder neck and urethra","volume":"102","author":"Grol","year":"2008","journal-title":"BJU Int."},{"key":"B7","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.regpep.2011.02.004","article-title":"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","volume":"167","author":"Heng","year":"2011","journal-title":"Regul. Pept."},{"key":"B8","doi-asserted-by":"publisher","first-page":"5905","DOI":"10.3390\/ijms25115905","article-title":"Substance P\u2019s impact on chronic pain and psychiatric conditions-A narrative review","volume":"25","author":"Humes","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"95","DOI":"10.2174\/1876386301306010095","article-title":"Resiniferatoxin for pain treatment: an interventional approach to personalized pain medicine","volume":"6","author":"Iadarola","year":"2013","journal-title":"open pain J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.2174\/156802611796904942","article-title":"The vanilloid agonist resiniferatoxin for interventional-based pain control","volume":"11","author":"Iadarola","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4049","DOI":"10.3390\/cells11244049","article-title":"Cutaneous injection of resiniferatoxin completely alleviates and prevents nerve-injury-induced neuropathic pain","volume":"11","author":"Javed","year":"2022","journal-title":"Cells"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e7021","DOI":"10.1371\/journal.pone.0007021","article-title":"Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal cord for long lasting analgesia","volume":"4","author":"Jeffry","year":"2009","journal-title":"PloS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1459683","DOI":"10.3389\/fphar.2024.1459683","article-title":"The role of TRPV1 in chronic prostatitis: a review","volume":"15","author":"Jiang","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.2174\/156802611796904924","article-title":"Therapeutic targeting of TRPV1 by resiniferatoxin, from preclinical studies to clinical trials","volume":"11","author":"Kissin","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1007\/s12031-012-9766-9","article-title":"Effect of surgical and chemical sensory denervation on non-neural expression of the transient receptor potential vanilloid 1 (TRPV1) receptors in the rat","volume":"48","author":"Kun","year":"2012","journal-title":"J. Mol. Neurosci. MN"},{"key":"B16","first-page":"636","article-title":"Evaluation of the lower urinary tract function using voiding spot assay in mice","volume":"75","author":"Luo","year":"2023","journal-title":"Sheng Li Xue Bao Acta Physiol. Sin."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1484980","DOI":"10.3389\/fnins.2024.1484980","article-title":"Enhancement sensitivity of TRPV1 in dorsal root ganglia via the SP-NK-1 pathway contributes to increased bladder organ sensitivity caused by prostatitis","volume":"18","author":"Luo","year":"2024","journal-title":"Front. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.neuroscience.2007.07.053","article-title":"Neural mechanisms of pelvic organ cross-sensitization","volume":"149","author":"Malykhina","year":"2007","journal-title":"Neuroscience"},{"key":"B19","doi-asserted-by":"publisher","first-page":"102870","DOI":"10.1016\/j.ceca.2024.102870","article-title":"TRPV1: receptor structure, activation, modulation and role in neuro-immune interactions and pain","volume":"119","author":"Maximiano","year":"2024","journal-title":"Cell. Calcium"},{"key":"B20","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1002\/pros.23794","article-title":"Long-lasting bladder overactivity and bladder afferent hyperexcitability in rats with chemically-induced prostatic inflammation","volume":"79","author":"Ni","year":"2019","journal-title":"Prostate"},{"key":"B21","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1002\/pros.23514","article-title":"Effect of tadalafil on chronic pelvic pain and prostatic inflammation in a rat model of experimental autoimmune prostatitis","volume":"78","author":"Okamoto","year":"2018","journal-title":"Prostate"},{"key":"B22","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/s0304-3959(98)00187-0","article-title":"Lack of involvement of capsaicin-sensitive primary afferents in nerve-ligation injury induced tactile allodynia in rats","volume":"79","author":"Ossipov","year":"1999","journal-title":"Pain"},{"key":"B23","doi-asserted-by":"publisher","first-page":"90","DOI":"10.5213\/inj.1836124.062","article-title":"Neurologic mechanisms underlying voiding dysfunction due to prostatitis in a rat model of nonbacterial prostatic inflammation","volume":"22","author":"Park","year":"2018","journal-title":"Int. Neurourol. J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1007\/s40266-021-00890-2","article-title":"Diagnostic and management strategies for patients with chronic prostatitis and chronic pelvic pain syndrome","volume":"38","author":"Pena","year":"2021","journal-title":"Drugs and Aging"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1053\/j.gastro.2005.09.013","article-title":"Cross-organ sensitization of lumbosacral spinal neurons receiving urinary bladder input in rats with inflamed colon","volume":"129","author":"Qin","year":"2005","journal-title":"Gastroenterology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1002\/pros.23913","article-title":"TRPV1 in experimental autoimmune prostatitis","volume":"80","author":"Roman","year":"2020","journal-title":"Prostate"},{"key":"B27","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1016\/j.juro.2016.03.077","article-title":"Chronic prostatitis induces bladder hypersensitivity and sensitizes bladder afferents in the mouse","volume":"196","author":"Schwartz","year":"2016","journal-title":"J. Urology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1111\/j.1460-9568.2008.06438.x","article-title":"Protein kinase C epsilon contributes to basal and sensitizing responses of TRPV1 to capsaicin in rat dorsal root ganglion neurons","volume":"28","author":"Srinivasan","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"15042","DOI":"10.3390\/ijms242015042","article-title":"\u2018Resiniferatoxin: nature\u2019s precision medicine to silence TRPV1-positive afferents","volume":"24","author":"Szallasi","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/s0031-6997(24)01403-0","article-title":"Vanilloid (Capsaicin) receptors and mechanisms","volume":"51","author":"Szallasi","year":"1999","journal-title":"Pharmacol. Rev."},{"key":"B31","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/s0006-8993(98)01168-8","article-title":"Effects of systemic resiniferatoxin treatment on substance P mRNA in rat dorsal root ganglia and substance P receptor mRNA in the spinal dorsal horn","volume":"815","author":"Szallasi","year":"1999","journal-title":"Brain Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1097\/00029330-200709020-00013","article-title":"Intrathecal administration of resiniferatoxin produces analgesia against prostatodynia in rats","volume":"120","author":"Tang","year":"2007","journal-title":"Chin. Med. J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e00001","DOI":"10.1097\/IMNA-D-22-00001","article-title":"Traditional Chinese medicine regulates inflammatory factors in chronic prostatitis\/chronic pelvic pain syndrome: a review","volume":"10","author":"Wang","year":"2023","journal-title":"Integr. Med. Nephrol. Androl."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1016\/j.biopha.2018.10.010","article-title":"Experimental rodent models of chronic prostatitis and evaluation criteria","volume":"108","author":"Wang","year":"2018","journal-title":"Biomed. and Pharmacother. = Biomedecine and Pharmacother."},{"key":"B35","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1742-2094-9-30","article-title":"Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat","volume":"9","author":"Xia","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"B36","doi-asserted-by":"publisher","first-page":"12067","DOI":"10.1523\/JNEUROSCI.0496-07.2007","article-title":"Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia","volume":"27","author":"Zhang","year":"2007","journal-title":"J. Neurosci. Official J. Soc. Neurosci."},{"key":"B37","first-page":"1021","article-title":"Correlation between activation of L5-S2 spinal cord astrocytes and effect of substance P in chronic prostatitis pain","volume":"15","author":"Zhang","year":"2009","journal-title":"Zhonghua Nan Ke Xue = Natl. J. Androl."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e13302","DOI":"10.1111\/and.13302","article-title":"Upregulation of TRPV1 in spinal dorsal root ganglion by activating NGF-TrkA pathway contributes to pelvic organ cross-sensitisation in rats with experimental autoimmune prostatitis","volume":"51","author":"Zhang","year":"","journal-title":"Andrologia"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1002\/pros.23866","article-title":"Effect of alcohol on chronic pelvic pain and prostatic inflammation in a mouse model of experimental autoimmune prostatitis","volume":"79","author":"Zhang","year":"","journal-title":"Prostate"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1541684\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T06:54:24Z","timestamp":1740466464000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1541684\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":39,"alternative-id":["10.3389\/fphar.2025.1541684"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1541684","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]},"article-number":"1541684"}}