{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T05:52:20Z","timestamp":1781416340224,"version":"3.54.1"},"reference-count":73,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Interstitial cystitis\/bladder pain syndrome (IC\/BPS) is a chronic condition causing bladder pressure and pain. The condition is of unknown etiology and is often accompanied by other symptoms, including chronic pelvic pain, increased urinary urgency, and frequency. There is no definitive diagnosis for IC\/BPS, and treatment options are currently limited to physical therapy and medications to help alleviate symptoms. The endogenous cannabinoid system (ECS) is an important regulator of numerous physiological systems, including the urinary system. Modulations of the ECS have been shown to be beneficial for IC\/BPS-associated pain and inflammation in rodents. As an attempt to identify potential biomarkers for IC\/BPS, we reviewed experimental studies where the components of the ECS have been quantified in experimental models of IC\/BPS. Further investigations using well-defined animal models and patients\u2019 data are required to obtain stronger evidence regarding the potential for ECS components to be definitive biomarkers for IC\/BPS.<\/jats:p>","DOI":"10.3390\/diagnostics12010019","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T10:16:18Z","timestamp":1640254578000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Components of the Endogenous Cannabinoid System as Potential Biomarkers for Interstitial Cystitis\/Bladder Pain Syndrome"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1929-0805","authenticated-orcid":false,"given":"Saki","family":"Sultana","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraint","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"},{"name":"Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-9168","authenticated-orcid":false,"given":"Christian","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"},{"name":"Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.5213\/inj.2142084.042","article-title":"Current Understanding and Future Perspectives of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"25","author":"Ueda","year":"2021","journal-title":"Int. Neurourol. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1177\/1756287218761574","article-title":"Current best practice management of interstitial cystitis\/bladder pain syndrome","volume":"10","author":"Han","year":"2018","journal-title":"Ther. Adv. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/iju.14234","article-title":"Clinical guidelines for interstitial cystitis\/bladder pain syndrome","volume":"27","author":"Homma","year":"2020","journal-title":"Int. J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/nau.20687","article-title":"Status of international consensus on interstitial cystitis\/bladder pain syndrome\/painful bladder syndrome: 2008 snapshot","volume":"28","author":"Hanno","year":"2009","journal-title":"Neurourol. Urodyn."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.juro.2006.09.032","article-title":"Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: A systematic review","volume":"177","author":"Bogart","year":"2007","journal-title":"J. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.juro.2009.12.103","article-title":"Development, validation and testing of an epidemiological case definition of interstitial cystitis\/painful bladder syndrome","volume":"183","author":"Berry","year":"2010","journal-title":"J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/iju.12311","article-title":"Potential urine and serum biomarkers for patients with bladder pain syndrome\/interstitial cystitis","volume":"21","author":"Kuo","year":"2014","journal-title":"Int. J. Urol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/00042307-200307000-00007","article-title":"Recent developments in the management of interstitial cystitis","volume":"13","author":"Bouchelouche","year":"2003","journal-title":"Curr. Opin. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/01.ju.0000146114.53828.82","article-title":"Prevalence and incidence of interstitial cystitis in a managed care population","volume":"173","author":"Clemens","year":"2005","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.juro.2011.10.040","article-title":"Comparison of an interstitial cystitis\/bladder pain syndrome clinical cohort with symptomatic community women from the RAND Interstitial Cystitis Epidemiology study","volume":"187","author":"Konkle","year":"2012","journal-title":"J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.juro.2011.03.132","article-title":"Prevalence of symptoms of bladder pain syndrome\/interstitial cystitis among adult females in the United States","volume":"186","author":"Berry","year":"2011","journal-title":"J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1207\/s15327655jchn2303_3","article-title":"Ambiguous chronic illness in women: Community health nursing concern","volume":"23","author":"Johnson","year":"2006","journal-title":"J. Community Health Nurs."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1016\/j.juro.2011.03.064","article-title":"AUA guideline for the diagnosis and treatment of interstitial cystitis\/bladder pain syndrome","volume":"185","author":"Hanno","year":"2011","journal-title":"J. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.juro.2015.01.086","article-title":"Diagnosis and treatment of interstitial cystitis\/bladder pain syndrome: AUA guideline amendment","volume":"193","author":"Hanno","year":"2015","journal-title":"J. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1016\/j.juro.2015.05.105","article-title":"Painful Bladder Filling and Painful Urgency are Distinct Characteristics in Men and Women with Urological Chronic Pelvic Pain Syndromes: A MAPP Research Network Study","volume":"194","author":"Lai","year":"2015","journal-title":"J. Urol."},{"key":"ref_16","first-page":"87","article-title":"Biomarkers for interstitial cystitis\/painful bladder syndrome","volume":"12","author":"Argade","year":"2016","journal-title":"Womens Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/14737159.2018.1412258","article-title":"Selecting analytical biomarkers for diagnostic applications: A first principles approach","volume":"18","author":"Byrnes","year":"2018","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_18","first-page":"S9","article-title":"Etiology, pathogenesis, and diagnosis of interstitial cystitis","volume":"4","author":"Sant","year":"2002","journal-title":"Rev. Urol."},{"key":"ref_19","first-page":"3599","article-title":"The role of the bladder surface in interstitial cystitis\/painful bladder syndrome","volume":"14","author":"Teichman","year":"2007","journal-title":"Can. J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.tcmj.2015.09.006","article-title":"Pathophysiology of interstitial cystitis\/bladder pain syndrome","volume":"27","author":"Ke","year":"2015","journal-title":"Tzu Chi Med. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/iju.13985","article-title":"Pathophysiology of interstitial cystitis","volume":"26","author":"Birder","year":"2019","journal-title":"Int. J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s00120-007-1480-9","article-title":"Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions","volume":"46","author":"Neuhaus","year":"2007","journal-title":"Urol. A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.urols.2015.02.002","article-title":"Biomarkers for patients with interstitial cystitis\/bladder pain syndrome","volume":"26","author":"Liu","year":"2015","journal-title":"Urol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.urology.2006.03.083","article-title":"Bladder defense molecules, urothelial differentiation, urinary biomarkers, and interstitial cystitis","volume":"69","author":"Hurst","year":"2007","journal-title":"Urology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"931","DOI":"10.3389\/fnins.2018.00931","article-title":"Mechanisms Underlying Overactive Bladder and Interstitial Cystitis\/Painful Bladder Syndrome","volume":"12","author":"Grundy","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"484.e7","DOI":"10.1016\/j.urology.2011.09.049","article-title":"Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis\/painful bladder syndrome","volume":"79","author":"Shie","year":"2012","journal-title":"Urology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/S0090-4295(03)00005-0","article-title":"Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis","volume":"61","author":"Keay","year":"2003","journal-title":"Urology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0022-5347(17)34944-3","article-title":"Decreased expression of a glycoprotein component of bladder surface mucin (GP1) in interstitial cystitis","volume":"151","author":"Moskowitz","year":"1994","journal-title":"J. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11803","DOI":"10.1073\/pnas.0404509101","article-title":"An antiproliferative factor from interstitial cystitis patients is a frizzled 8 protein-related sialoglycopeptide","volume":"101","author":"Keay","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/S0022-5347(05)68345-0","article-title":"Antiproliferative activity is present in bladder but not renal pelvic urine from interstitial cystitis patients","volume":"162","author":"Keay","year":"1999","journal-title":"J. Urol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1152\/physiolgenomics.00055.2003","article-title":"Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment","volume":"14","author":"Keay","year":"2003","journal-title":"Physiol. Genom."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1464-410X.2008.08097.x","article-title":"Heparin-binding epidermal growth factor-like growth factor functionally antagonizes interstitial cystitis antiproliferative factor via mitogen-activated protein kinase pathway activation","volume":"103","author":"Kim","year":"2009","journal-title":"BJU Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/S0022-5347(05)67638-0","article-title":"Bladder stretch alters urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis","volume":"163","author":"Chai","year":"2000","journal-title":"J. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.urology.2003.08.024","article-title":"Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor in men with interstitial cystitis versus chronic pelvic pain syndrome","volume":"63","author":"Keay","year":"2004","journal-title":"Urology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0090-4295(01)01127-X","article-title":"Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor as urine markers for interstitial cystitis","volume":"57","author":"Keay","year":"2001","journal-title":"Urology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1046\/j.1464-410X.1997.00097.x","article-title":"Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis","volume":"79","author":"Lowe","year":"1997","journal-title":"Br. J. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1757-5672.2010.00065.x","article-title":"Urinary Nerve Growth Factor Levels in Urinary Tract Diseases with or without Frequency Urgency Symptoms","volume":"2","author":"Kuo","year":"2010","journal-title":"Low Urin. Tract Symptoms"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1111\/j.1464-410X.2009.08675.x","article-title":"Urinary nerve growth factor level is increased in patients with interstitial cystitis\/bladder pain syndrome and decreased in responders to treatment","volume":"104","author":"Liu","year":"2009","journal-title":"BJU Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.juro.2014.05.047","article-title":"Correlation of Gene Expression with Bladder Capacity in Interstitial Cystitis\/Bladder Pain Syndrome","volume":"192","author":"Colaco","year":"2014","journal-title":"J. Urol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00192-009-0822-0","article-title":"Genome-based expression profiles as a single standardized microarray platform for the diagnosis of bladder pain syndrome\/interstitial cystitis: An array of 139 genes model","volume":"20","author":"Tseng","year":"2009","journal-title":"Int. Urogynecol. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1124\/pr.58.3.2","article-title":"The endocannabinoid system as an emerging target of pharmacotherapy","volume":"58","author":"Pacher","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1038\/sj.ijo.0803272","article-title":"The pharmacology of cannabinoid receptors and their ligands: An overview","volume":"30","author":"Pertwee","year":"2006","journal-title":"Int. J. Obes."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.irn.2015.10.001","article-title":"The Endocannabinoid Signaling System in the CNS: A Primer","volume":"125","author":"Hillard","year":"2015","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s41232-018-0086-5","article-title":"Endocannabinoids and related N-acylethanolamines: Biological activities and metabolism","volume":"38","author":"Tsuboi","year":"2018","journal-title":"Inflamm. Regen."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.biopsych.2015.07.028","article-title":"An Introduction to the Endogenous Cannabinoid System","volume":"79","author":"Lu","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.3389\/fphar.2021.708989","article-title":"Endoca.annabinoids in Bladder Sensory Mechanisms in Health and Diseases","volume":"12","author":"Christie","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/nau.22442","article-title":"Cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction","volume":"33","author":"Hedlund","year":"2014","journal-title":"Neurourol. Urodyn."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.eururo.2011.09.002","article-title":"Expression of fatty acid amide hydrolase (FAAH) in human, mouse, and rat urinary bladder and effects of FAAH inhibition on bladder function in awake rats","volume":"61","author":"Strittmatter","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.neulet.2008.08.076","article-title":"Cannabinoid receptor 2 is increased in acutely and chronically inflamed bladder of rats","volume":"445","author":"Merriam","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"R846","DOI":"10.1152\/ajpregu.00585.2012","article-title":"Activation of cannabinoid receptor 2 inhibits experimental cystitis","volume":"304","author":"Wang","year":"2013","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1016\/j.juro.2008.11.079","article-title":"Distribution and function of cannabinoid receptors 1 and 2 in the rat, monkey and human bladder","volume":"181","author":"Gratzke","year":"2009","journal-title":"J. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.juro.2008.11.078","article-title":"Differential expression of functional cannabinoid receptors in human bladder detrusor and urothelium","volume":"181","author":"Tyagi","year":"2009","journal-title":"J. Urol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"26","DOI":"10.4103\/0970-1591.60440","article-title":"Functional role of cannabinoid receptors in urinary bladder","volume":"26","author":"Tyagi","year":"2010","journal-title":"Indian J. Urol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.eururo.2010.02.027","article-title":"Effects of cannabinor, a novel selective cannabinoid 2 receptor agonist, on bladder function in normal rats","volume":"57","author":"Gratzke","year":"2010","journal-title":"Eur. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1744-8069-7-31","article-title":"Local activation of cannabinoid CB\u2081 receptors in the urinary bladder reduces the inflammation-induced sensitization of bladder afferents","volume":"7","author":"Walczak","year":"2011","journal-title":"Mol. Pain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1016\/j.juro.2009.12.093","article-title":"TRPA1 receptor induced relaxation of the human urethra involves TRPV1 and cannabinoid receptor mediated signals, and cyclooxygenase activation","volume":"183","author":"Weinhold","year":"2010","journal-title":"J. Urol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fnsys.2018.00017","article-title":"Potential of Endocannabinoids to Control Bladder Pain","volume":"12","author":"Bjorling","year":"2018","journal-title":"Front. Syst. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.juro.2013.10.102","article-title":"Treatment with a cannabinoid receptor 2 agonist decreases severity of established cystitis","volume":"191","author":"Wang","year":"2014","journal-title":"J. Urol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0304-3959(01)00419-5","article-title":"Attenuation of nerve growth factor-induced visceral hyperalgesia via cannabinoid CB(1) and CB(2)-like receptors","volume":"97","author":"Jaggar","year":"2002","journal-title":"Pain"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1038\/sj.bjp.0703229","article-title":"Effects of cannabinoid receptor agonists on neuronally-evoked contractions of urinary bladder tissues isolated from rat, mouse, pig, dog, monkey and human","volume":"129","author":"Martin","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0304-3959(98)00041-4","article-title":"The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain","volume":"76","author":"Jaggar","year":"1998","journal-title":"Pain"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1097\/00000542-200103000-00023","article-title":"Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder","volume":"94","author":"Rice","year":"2001","journal-title":"Anesthesiology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.juro.2014.11.083","article-title":"Protective effect of palmitoylethanolamide in a rat model of cystitis","volume":"193","author":"Pessina","year":"2015","journal-title":"J. Urol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ejphar.2014.02.013","article-title":"Evaluation of selective cannabinoid CB(1) and CB(2) receptor agonists in a mouse model of lipopolysaccharide-induced interstitial cystitis","volume":"729","author":"Tambaro","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/nau.24205","article-title":"Cannabinoid receptor 2 activation decreases severity of cyclophosphamide-induced cystitis via regulating autophagy","volume":"39","author":"Liu","year":"2020","journal-title":"Neurourol. Urodyn."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lowe, H., Toyang, N., Steele, B., Bryant, J., and Ngwa, W. (2021). The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179472"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00210-019-01729-9","article-title":"Fatty acid amide hydrolase inhibition normalises bladder function and reduces pain through normalising the anandamide\/palmitoylethanolamine ratio in the inflamed bladder of rats","volume":"393","author":"Charrua","year":"2020","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/j.1464-410X.2010.09583.x","article-title":"Inhibition of fatty acid amide hydrolase suppresses referred hyperalgesia induced by bladder inflammation","volume":"108","author":"Merriam","year":"2011","journal-title":"BJU Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1007\/s12031-014-0453-x","article-title":"Attenuation of Cystitis and Pain Sensation in Mice Lacking Fatty Acid Amide Hydrolase","volume":"55","author":"Wang","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"11253","DOI":"10.1523\/JNEUROSCI.2657-04.2004","article-title":"Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis","volume":"24","author":"Dinis","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrurol.2016.110","article-title":"The endocannabinoid system\u2014A target for the treatment of LUTS?","volume":"13","author":"Hedlund","year":"2016","journal-title":"Nat. Rev. Urol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1514.e15","DOI":"10.1016\/j.urology.2009.12.051","article-title":"Increased Cannabinoid Receptor 1-Immunoreactive Nerve Fibers in Overactive and Painful Bladder Disorders and Their Correlation with Symptoms","volume":"75","author":"Mukerji","year":"2010","journal-title":"Urology"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Vago, R., Ravelli, A., Bettiga, A., Casati, S., Lavorgna, G., Benigni, F., Salonia, A., Montorsi, F., Orioli, M., and Ciuffreda, P. (2020). Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage. Cancers, 12.","DOI":"10.3390\/cancers12040870"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/1\/19\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:45Z","timestamp":1760169105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/1\/19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["diagnostics12010019"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12010019","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,23]]}}}