Yoshimura Naoki
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Neurourol Urodyn. 2007 Oct;26(6 Suppl):908-13. doi: 10.1002/nau.20487.
Dysregulation of bladder afferent activity and detrusor smooth muscle behavior leads to a constellation of lower urinary tract symptoms (LUTS), which includes overactive bladder (OAB). Current treatments for LUTS are poorly tolerated and may be associated with substantial adverse effects.
Major advances in the understanding of bladder neuroanatomy and the role of bladder afferent pathways in symptom generation suggest a range of targets for new therapeutic agents.
A sensory role for urothelial and suburothelial structures has been established, as well as a cascade of afferent bladder signaling involving the bladder epithelium and detrusor muscle. Numerous inhibitory and stimulatory neurotransmitters and chemical mediators interact with a variety of specialized receptors and participate in signal transduction leading to wider neuroactivation. The blockade of muscarinic receptors, possibly mediated by muscarinic 2 (M(2)) receptors residing in the urothelium, has been shown to affect bladder afferent fibers, challenging the traditional concept that antimuscarinic therapy involves M(3) receptor-mediated effects on detrusor smooth muscle. The propagation of impulses to spinal and higher centers utilizes axonal fiber tracts remarkable for their morphologic and functional plasticity as bladder function becomes increasingly disordered.
These findings suggest that the etiology of LUTS includes enhanced, dysregulated, and perhaps maladaptive sensory signaling arising from numerous pelvic locales, including the most superficial epithelium of the bladder.
膀胱传入活动和逼尿肌平滑肌行为失调会导致一系列下尿路症状（LUTS），其中包括膀胱过度活动症（OAB）。目前针对LUTS的治疗耐受性差，且可能伴有严重的不良反应。
在膀胱神经解剖学理解以及膀胱传入通路在症状产生中的作用方面取得的重大进展提示了一系列新型治疗药物的靶点。
已确定尿路上皮和尿路上皮下结构具有感觉功能，以及涉及膀胱上皮和逼尿肌的一系列膀胱传入信号传导。多种抑制性和刺激性神经递质及化学介质与各种特殊受体相互作用，并参与导致更广泛神经激活的信号转导。已表明，可能由存在于尿路上皮中的毒蕈碱2（M(2)）受体介导的毒蕈碱受体阻断会影响膀胱传入纤维，这对传统观念即抗毒蕈碱疗法涉及M(3)受体介导的对逼尿肌平滑肌的作用提出了挑战。随着膀胱功能变得越来越紊乱，向脊髓和更高中枢的冲动传播利用了以其形态和功能可塑性而著称的轴突纤维束。
这些发现表明，LUTS的病因包括来自包括膀胱最表层上皮在内的多个盆腔部位的增强、失调以及可能适应不良的感觉信号传导。
