Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury.
Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.
Furuta
Akira
A
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213-3221, USA.
Kita
Masafumi
M
Suzuki
Yasuyuki
Y
Egawa
Shin
S
Chancellor
Michael B
MB
de Groat
William C
WC
Yoshimura
Naoki
N
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D066298:In Vitro Techniques; D008026:Ligation; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism; D059348:Peripheral Nerve Injuries; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000503:physiopathology*; D014550:Urinary Incontinence, Stress / Q000209:etiology / Q000503:physiopathology*
D000316:Adrenergic alpha-Agonists; D018721:Muscarinic Agonists; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D002217:Carbachol; D002211:Capsaicin