{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:31:58Z","timestamp":1784759518106,"version":"3.55.0"},"reference-count":162,"publisher":"American Physiological Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2014,6,15]]},"abstract":"<jats:p>Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)\/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS\/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS\/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered.<\/jats:p>","DOI":"10.1152\/ajpregu.00030.2014","type":"journal-article","created":{"date-parts":[[2014,4,24]],"date-time":"2014-04-24T09:51:09Z","timestamp":1398333069000},"page":"R869-R878","source":"Crossref","is-referenced-by-count":33,"title":["Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function"],"prefix":"10.1152","volume":"306","author":[{"given":"Eric J.","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana","family":"Merrill","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Vizzard","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.3"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/nau.21212"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1042\/CS20050161"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(01)01637-5"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ncpuro0021"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09650.x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22465"},{"key":"B8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3410\/B2-12","volume":"2","author":"Angelico P","year":"2010","journal-title":"F1000 Biol Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-16499-6_19"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00496-1"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-006-0073-2"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-19-07353.2000"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2012"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.125435"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12011"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231243698"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nn902"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00118.2004"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00734.2005"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1998.0719"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.01.053"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1992.tb15791.x"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-3-31"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.12.006"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5462-09.2010"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00321.2006"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)66587-1"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.275.4.R1279"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.139147"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00211.2007"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/BF01945358"},{"key":"B32","first-page":"227","volume-title":"The Autonomic Nervous System","author":"de Groat WC","year":"1993"},{"key":"B33","first-page":"369","volume-title":"J Autonom Nerv Syst","author":"de Groat WC","year":"1986"},{"key":"B34","first-page":"219","volume-title":"Basic and Clinical Aspects of Chronic Abdominal Pain Pain Research and Clinical Management","author":"de Groat WC","year":"1993"},{"key":"B35","first-page":"347","volume-title":"Advances in Neurology","author":"de Groat WC","year":"1997"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(81)90059-X"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)61860-9"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(96)02993-4"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00575-1"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90237-V"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(83)90168-5"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/75.2.125"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)65931-9"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007043132537"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1977.tb10387.x"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1159\/000282414"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20511"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005333107"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00474-0"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.503bb.x"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706637"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.7.1213"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2401"},{"key":"B54","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0031-6997(25)06782-1","volume":"46","author":"Fredholm BB","year":"1994","journal-title":"Pharmacol Rev"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)90328-7"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31766"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-013-0033-5"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-008-9104-4"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1080\/003655902320765926"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.09.026"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00728.2007"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp018117"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01871.x"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706832"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000155170.15023.e5"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)36252-3"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-007-0197-z"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/83.3.442"},{"key":"B69","first-page":"A57","volume":"13","author":"Jennings LJ","year":"1999","journal-title":"FASEB J"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.07-03-00923.1987"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)02233-7"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200107200-00034"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1007\/BF00318197"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903190411"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-4096.2003.05059.x"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2005.01140.x"},{"key":"B77","volume-title":"Concise text of Neuroscience","author":"Kingsley RE","year":"1996"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90718.2008"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1965.45.3.425"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2004.01.001"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1515\/REVNEURO.1992.3.1.1"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2004.08.007"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67618-5"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(93)90092-Z"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00143-4"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/330658a0"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1990.tb00431.x"},{"key":"B88","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1111\/j.1464-410X.2008.07757.x","volume":"102","author":"Liu HT","year":"2008","journal-title":"BJU Int"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2008.04.037"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2007.04.038"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.01.146"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2008.01.069"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410X.1997.00097.x"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064913"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19971229)389:4<584::AID-CNE4>3.0.CO;2-X"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.09.077"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.531bb.x"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90323-9"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90250-X"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2004.04.008"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.020206"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2012.09.011"},{"key":"B103","first-page":"244","volume":"162","author":"Nilius B","year":"2007","journal-title":"Bull Mem Acad R Med Belg"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2006"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2005.06.099"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2002"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)61915-3"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1126\/science.2011743"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64631-9"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112929"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10447"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10283"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.4A6556.2005"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-003-0579-3"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.2.622"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00074-10"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00367.2009"},{"key":"B118","first-page":"37","volume":"77","author":"Smet PJ","year":"1997","journal-title":"Lab Invest"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903100309"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)41846-5"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115488"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(86)90066-7"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2006.06200.x"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00133.2008"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)65726-6"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(93)90051-4"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2280"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2004.04858.x"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.139295"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91341-B"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(94)90134-1"},{"key":"B132","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s00345-002-0287-y","volume":"20","author":"Uckert S","year":"2002","journal-title":"World J Urol"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1016\/1043-6618(92)90701-C"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142819"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703720"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-0618(00)00115-0"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.278.4.R1027"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7254"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1159\/000111212"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.279.1.R295"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(20000508)420:3<335::AID-CNE5>3.0.CO;2-#"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960624)370:2<191::AID-CNE5>3.0.CO;2-Y"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-05-04033.1995"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00137-8"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(93)90382-5"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90486-5"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)90090-6"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-15-05670.2001"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1124\/mol.109.055624"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24086"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.03.020"},{"key":"B152","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s00441-002-0673-1","volume":"311","author":"Wanigasekara Y","year":"2003","journal-title":"Cell Tissue Res"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701148"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903510302"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00774-5"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2008.951962"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3023-06.2006"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-11-04644.1999"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(01)01639-9"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-219006"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00592.2007"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6793-7-9"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00030.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T14:58:46Z","timestamp":1746197926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00030.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,15]]},"references-count":162,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2014,6,15]]}},"alternative-id":["10.1152\/ajpregu.00030.2014"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00030.2014","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,15]]}}}