Increased Cannabinoid Receptor 1-Immunoreactive Nerve Fibers in Overactive and Painful Bladder Disorders and Their Correlation With Symptoms

OBJECTIVE To study the expression of cannabinoid receptor 1 (CB(1)) in human urinary bladder hypersensitivity and overactivity disorders, and correlate changes with symptoms. Cannabinoid receptor agonists have been shown to modulate urinary bladder contractility and reduce pain after bladder inflammation; their clinical efficacy on lower urinary tract symptoms was demonstrated in the Cannabinoids in Multiple Sclerosis study. METHODS Bladder tissue specimens were obtained from patients with painful bladder syndrome (PBS, n = 13), idiopathic detrusor overactivity (IDO, n = 14), and from controls with asymptomatic microscopic hematuria (n = 16). The severity of symptoms was assessed using the Pelvic Pain and Urgency/Frequency Questionnaire. Pain score was also recorded on a visual analogue scale. Specimens were immunostained using specific antibodies to CB(1) and to neurofilaments as a structural maker. Detrusor and suburothelial nerve fiber density was quantified with a visual grading scale. The immunohistochemistry results were correlated with Pain, Frequency, and Urgency scores. RESULTS CB(1)-immunoreative nerve fibers were significantly increased in the suburothelium of PBS (P = .0123) and IDO (P = .0013) specimens, and in detrusor layer in IDO (P = .0003), as compared with controls. CB(1)-immunoreactive suburothelial nerve fiber density correlated significantly with pain scores (Visual Analogue Scale) in PBS (r = .6878, P = .0347) and urgency scores in IDO (r = .6623, P = .0027). Neurofilaments-immunoreactive suburothelial nerve fibers were significantly increased in PBS (P = .019) and IDO (P = .05). CONCLUSIONS The results of this study suggest that increased nerve fibers, which express CB(1), may be related to bladder pain in PBS and urgency in IDO. Our findings support clinical trials of CB(1) agonists in bladder disorders. UROLOGY 75: 1514.e15-1514.e20, 2010. (c) 2010 Elsevier Inc.