Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford A P D W, Davis J B, Dasgupta P, Fowler C J, Anand P
Peripheral Neuropathy Unit, Hammersmith Hospital, Imperial College London, United Kingdom.
J Urol. 2005 Sep;174(3):977-82; discussion 982-3. doi: 10.1097/01.ju.0000169481.42259.54.
Botulinum neurotoxin type A (BoNT/A) is effective in the treatment of intractable detrusor overactivity (DO). In addition to its known inhibitory effect on presynaptic release of acetylcholine by motor terminals, there is increasing evidence that BoNT/A may affect sensory fibers. We investigated a possible effect of BoNT/A on human bladder afferent mechanisms by studying the sensory receptors P2X3 and TRPV1 in biopsies from patients with neurogenic or idiopathic DO.
A total of 38 patients (22 with neurogenic DO, 16 with idiopathic DO) with intractable DO were treated with intradetrusor BoNT/A, and bladder biopsies were taken at 4 and 16 weeks. Urodynamics and voiding diary were also recorded. Specimens were studied immunohistochemically for P2X3, TRPV1 and the pan-neuronal marker PGP9.5, in comparison with controls.
P2X3-immunoreactive and TRPV1-immunoreactive (-IR) fibers were decreased at 4 weeks after BoNT/A, and more significantly at 16 weeks (paired t test p=0.0004 and p=0.0008, respectively), when significant improvements were observed in clinical and urodynamic parameters. P2X3-IR fiber decrease was significantly correlated with reduction of urgency episodes at 4 and 16 weeks (p=0.0013 at 4 weeks and p=0.02 at 16 weeks), but not maximum cystometric capacity or detrusor pressures. TRPV1-IR fiber decrease showed a similar trend. PGP9.5-IR suburothelial fibers remained unchanged after treatment at both followups (p=0.85 and p=0.21 at 4 and 16 weeks, respectively). Urothelial cell P2X3-IR and TRPV1-IR also appeared unchanged.
Decreased levels of sensory receptors P2X3 and/or TRPV1 may contribute to the clinical effect of BoNT/A in detrusor overactivity.
A型肉毒杆菌神经毒素（BoNT/A）在治疗顽固性逼尿肌过度活动（DO）方面有效。除了其对运动终板乙酰胆碱突触前释放的已知抑制作用外，越来越多的证据表明BoNT/A可能会影响感觉纤维。我们通过研究神经源性或特发性DO患者活检组织中的感觉受体P2X3和瞬时受体电位香草酸亚型1（TRPV1），来探究BoNT/A对人膀胱传入机制的可能影响。
总共38例患有顽固性DO的患者（22例神经源性DO，16例特发性DO）接受了膀胱逼尿肌内注射BoNT/A治疗，并在4周和16周时进行膀胱活检。同时记录尿动力学和排尿日记。与对照组相比，对标本进行P2X3、TRPV1和泛神经元标志物PGP9.5的免疫组织化学研究。
BoNT/A治疗后4周，P2X3免疫反应性和TRPV1免疫反应性（-IR）纤维减少，16周时更显著（配对t检验，p分别为0.0004和0.0008），此时临床和尿动力学参数有显著改善。P2X3-IR纤维减少与4周和16周时尿急发作次数的减少显著相关（4周时p = 0.0013，16周时p = 0.02），但与最大膀胱测压容量或逼尿肌压力无关。TRPV1-IR纤维减少呈现类似趋势。在两次随访中，治疗后PGP9.5-IR膀胱上皮下纤维均保持不变（4周和16周时p分别为0.85和0.21）。膀胱上皮细胞P2X3-IR和TRPV1-IR也未出现变化。
感觉受体P2X3和/或TRPV1水平降低可能有助于BoNT/A对逼尿肌过度活动的临床疗效。
