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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.
To review systematically the clinical evidence on strategies to prevent and manage autonomic dysreflexia (AD). A key word search of several databases (Medline, CINAHL, EMBASE, and PsycINFO), in addition to manual searches of retrieved articles, was undertaken to identify all English-language literature evaluating the efficacy of interventions for AD. Studies selected for review included randomized controlled trials (RCTs), prospective cohort studies, and cross-sectional studies. Treatments reviewed included pharmacologic and nonpharmacologic interventions for the management of AD in subjects with spinal cord injury. Studies that failed to assess AD outcomes (eg, blood pressure) or symptoms (eg, headaches, sweating) were excluded. Studies were critically reviewed and assessed for their methodologic quality by 2 independent reviewers. Thirty-one studies were assessed, including 6 RCTs. Preventative strategies to reduce the episodes of AD caused by common triggers (eg, urogenital system, surgery) primarily were supported by level 4 (pre-post studies) and level 5 (observational studies) evidence. The initial acute nonpharmacologic management of an episode of AD (ie, positioning the patient upright, loosening tight clothing, eliminating any precipitating stimulus) is supported by clinical consensus and physiologic data (level 5 evidence). The use of antihypertensive drugs in the presence of sustained elevated blood pressure is supported by level 1 (prazosin) and level 2 evidence (nifedipine and prostaglandin E(2)). A variety of options are available to prevent AD (eg, surgical, pharmacologic) and manage the acute episode (elimination of triggers, pharmacologic); however, these options are predominantly supported by evidence from noncontrolled trials, and more rigorous trials are required.
