{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:26:12Z","timestamp":1789647972215,"version":"4.0.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"crossref","award":["No. 7182058"],"award-info":[{"award-number":["No. 7182058"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Urol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Activation of mast cells plays an important role in the pathogenesis of bladder pain syndrome\/interstitial cystitis (BPS\/IC). Histamine, a mast cell-derived mediators, induced inflammation and hypersensitivity of the bladder. The present study investigated the expressions of histamine receptors in the bladder wall tissues of patients with BPS\/IC, and its association with the effectiveness of antihistamine therapy and disease symptoms.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Bladder tissues were collected from 69 BPS\/IC patients and 10 control female patients. The expression of H3R in BPS\/IC was further examined in an independent cohort of 10 female patients with BPS\/IC and another 10 age-matched female patients. Immunohistochemistry, Western blotting, and quantitative RT-PCR were performed to quantify the expressions of histamine receptors. Statistical analyses of the correlation of histamine receptor expression with antihistamine therapy outcome and severity of disease symptoms were also performed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The expression of four histamine receptors was significantly elevated in BPS\/IC (H1R, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; H2R, <jats:italic>P<\/jats:italic>\u2009=\u20090.031; H3R, <jats:italic>P<\/jats:italic>\u2009=\u20090.008; H4R, <jats:italic>P<\/jats:italic>\u2009=\u20090.048). Western blotting revealed that H3R were significantly reduced in the patients, whereas the mRNA levels of H3R were significantly increased. The patients were further divided into antihistamine responders (<jats:italic>n<\/jats:italic>\u2009=\u200938) and nonresponders (<jats:italic>n<\/jats:italic>\u2009=\u200922). No significant correlation was found in the expression of histamine receptors between responder and nonresponder groups. However, significant correlations between OLS and H1R (<jats:italic>P<\/jats:italic>\u2009=\u20090.003) and H3R (<jats:italic>P<\/jats:italic>\u2009=\u20090.045) were found.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The present study showed that expression of all the 4 histamine receptors were elevated in BPS\/IC. There were no statistical significant correlations between the expression levels of the four different histamine receptors and the treatment outcome of antihistamine therapy (amtitriptyline or cimetidine).<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12894-019-0548-3","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T16:03:06Z","timestamp":1573574586000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Differential expression of histamine receptors in the bladder wall tissues of patients with bladder pain syndrome\/interstitial cystitis \u2013 significance in the responsiveness to antihistamine treatment and disease symptoms"],"prefix":"10.1186","volume":"19","author":[{"given":"Hui","family":"Shan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Er-Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Dong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"issue":"1","key":"548_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.eururo.2007.09.019","volume":"53","author":"JP van de Merwe","year":"2008","unstructured":"van de Merwe JP, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome\/interstitial cystitis: an ESSIC proposal. Eur Urol. 2008;53(1):60\u20137.","journal-title":"Eur Urol"},{"issue":"6","key":"548_CR2","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1097\/01.ju.0000181203.82693.95","volume":"174","author":"MT Rosenberg","year":"2005","unstructured":"Rosenberg MT, Hazzard M. Prevalence of interstitial cystitis symptoms in women: a population based study in the primary care office. J Urol. 2005;174(6):2231\u20134.","journal-title":"J Urol"},{"issue":"2","key":"548_CR3","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s11255-007-9181-2","volume":"39","author":"IA Ibrahim","year":"2007","unstructured":"Ibrahim IA, et al. Prevalence of self-reported interstitial cystitis (IC) and interstitial-cystitis-like symptoms among adult women in the community. Int Urol Nephrol. 2007;39(2):489\u201395.","journal-title":"Int Urol Nephrol"},{"issue":"4","key":"548_CR4","first-page":"3599","volume":"14","author":"JM Teichman","year":"2007","unstructured":"Teichman JM, Moldwin R. The role of the bladder surface in interstitial cystitis\/painful bladder syndrome. Can J Urol. 2007;14(4):3599\u2013607.","journal-title":"Can J Urol"},{"issue":"4 Suppl","key":"548_CR5","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.urology.2006.08.1109","volume":"69","author":"GR Sant","year":"2007","unstructured":"Sant GR, et al. The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis. Urology. 2007;69(4 Suppl):34\u201340.","journal-title":"Urology"},{"issue":"6 Suppl 1","key":"548_CR6","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0090-4295(01)01129-3","volume":"57","author":"TC Theoharides","year":"2001","unstructured":"Theoharides TC, Kempuraj D, Sant GR. Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology. 2001;57(6 Suppl 1):47\u201355.","journal-title":"Urology"},{"issue":"2","key":"548_CR7","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.iac.2006.02.006","volume":"26","author":"M Jutel","year":"2006","unstructured":"Jutel M, Blaser K, Akdis CA. Histamine receptors in immune regulation and allergen-specific immunotherapy. Immunol Allergy Clin N Am. 2006;26(2):245\u201359 vii.","journal-title":"Immunol Allergy Clin N Am"},{"issue":"1","key":"548_CR8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrd2465","volume":"7","author":"RL Thurmond","year":"2008","unstructured":"Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nature reviews. Drug Des Discov. 2008;7(1):41\u201353.","journal-title":"Drug Des Discov"},{"issue":"17","key":"548_CR9","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.1517\/14656560802519845","volume":"9","author":"TC Theoharides","year":"2008","unstructured":"Theoharides TC, et al. Interstitial cystitis: bladder pain and beyond. Expert Opin Pharmacother. 2008;9(17):2979\u201394.","journal-title":"Expert Opin Pharmacother"},{"issue":"2","key":"548_CR10","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1007\/s00345-006-0079-x","volume":"24","author":"J Neuhaus","year":"2006","unstructured":"Neuhaus J, et al. Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes. World J Urol. 2006;24(2):202\u20139.","journal-title":"World J Urol"},{"issue":"5A Suppl","key":"548_CR11","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/S0090-4295(99)80333-1","volume":"49","author":"MP O'Leary","year":"1997","unstructured":"O'Leary MP, et al. The interstitial cystitis symptom index and problem index. Urology. 1997;49(5A Suppl):58\u201363.","journal-title":"Urology"},{"issue":"4","key":"548_CR12","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1097\/01.mou.0000232048.81965.16","volume":"16","author":"BR Toft","year":"2006","unstructured":"Toft BR, Nordling J. Recent developments of intravesical therapy of painful bladder syndrome\/interstitial cystitis: a review. Curr Opin Urol. 2006;16(4):268\u201372.","journal-title":"Curr Opin Urol"},{"issue":"1","key":"548_CR13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.urology.2003.08.024","volume":"63","author":"S Keay","year":"2004","unstructured":"Keay S, et al. Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor in men with interstitial cystitis versus chronic pelvic pain syndrome. Urology. 2004;63(1):22\u20136.","journal-title":"Urology"},{"issue":"Pt 2","key":"548_CR14","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1113\/jphysiol.2007.139352","volume":"583","author":"E Breunig","year":"2007","unstructured":"Breunig E, et al. Histamine excites neurones in the human submucous plexus through activation of H1, H2, H3 and H4 receptors. J Physiol. 2007;583(Pt 2):731\u201342.","journal-title":"J Physiol"},{"key":"548_CR15","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.brainres.2008.11.018","volume":"1250","author":"MI Strakhova","year":"2009","unstructured":"Strakhova MI, et al. Localization of histamine H4 receptors in the central nervous system of human and rat. Brain Res. 2009;1250:41\u20138.","journal-title":"Brain Res"},{"issue":"1","key":"548_CR16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1067\/mai.2003.1585","volume":"112","author":"CA Akdis","year":"2003","unstructured":"Akdis CA, Blaser K. Histamine in the immune regulation of allergic inflammation. J Allergy Clin Immunol. 2003;112(1):15\u201322.","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"548_CR17","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1111\/j.1365-2222.2007.02666.x","volume":"37","author":"M Jutel","year":"2007","unstructured":"Jutel M, Akdis CA. Histamine as an immune modulator in chronic inflammatory responses. Clin Exp Allergy. 2007;37(3):308\u201310.","journal-title":"Clin Exp Allergy"},{"issue":"1","key":"548_CR18","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.pbb.2007.07.014","volume":"88","author":"KE Cannon","year":"2007","unstructured":"Cannon KE, Leurs R, Hough LB. Activation of peripheral and spinal histamine H3 receptors inhibits formalin-induced inflammation and nociception, respectively. Pharmacol Biochem Behav. 2007;88(1):122\u20139.","journal-title":"Pharmacol Biochem Behav"},{"issue":"1\u20133","key":"548_CR19","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.ejphar.2007.02.026","volume":"563","author":"G Coruzzi","year":"2007","unstructured":"Coruzzi G, et al. Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation. Eur J Pharmacol. 2007;563(1\u20133):240\u20134.","journal-title":"Eur J Pharmacol"}],"container-title":["BMC Urology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12894-019-0548-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12894-019-0548-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12894-019-0548-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:10:08Z","timestamp":1605053408000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcurol.biomedcentral.com\/articles\/10.1186\/s12894-019-0548-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,12]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["548"],"URL":"https:\/\/doi.org\/10.1186\/s12894-019-0548-3","relation":{},"ISSN":["1471-2490"],"issn-type":[{"value":"1471-2490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,12]]},"assertion":[{"value":"9 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This research was approved by the Ethics Committee of Beijing Chaoyang Hospital. All methods were carried out in accordance with relevant guidelines and regulations. The study design was approved by the ethnic committee of our hospital, with informed consents obtained from all the participants.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"115"}}