Effects of intravesical onabotulinumtoxinA on bladder dysfunction and autonomic dysreflexia after spinal cord injury: role of nerve growth factor

• Published in: BJU international 2012-02, Vol.109 (3), p.402-407
• Main Authors: Elkelini, Mohamed S., Bagli, Darius J., Fehlings, Michael, Hassouna, Magdy
• Format: Article
• Language: English
• Subjects: Administration, Intravesical; Animals; autonomic dysreflexia; Autonomic Dysreflexia - drug therapy; Biological and medical sciences; Bladder; Blood Pressure - drug effects; Botulinum Toxins, Type A - administration & dosage; Botulinum Toxins, Type A - pharmacology; Cerebrospinal fluid. Meninges. Spinal cord; Female; Heart Rate - drug effects; Medical sciences; Nephrology. Urinary tract diseases; nerve growth factor; Nerve Growth Factor - metabolism; Nerve Growth Factor - physiology; Nervous system (semeiology, syndromes); neurogenic bladder overactivity; Neurology; Neuromuscular Agents - administration & dosage; Neuromuscular Agents - pharmacology; onabotulinumtoxinA; Rats; Rats, Sprague-Dawley; Rodents; Spinal cord injuries; Spinal Cord Injuries - complications; spinal cord injury; Urinary Bladder, Neurogenic - drug therapy; Urinary Bladder, Overactive - drug therapy; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Urination - physiology
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2011.010362.x

Study Type – Aetiology (case control) Level of Evidence 3c What's known on the subject? and What does the study add? Neurogenic detrusor overactivity (NDO) and autonomic dysreflexia (AD) are common outcomes following spinal cord injury (SCI). In this study, we showed that onabotulinumtoxinA controlled NDO and AD in rats with T4‐SCI, and also provided a mechanism for the control of AS. OBJECTIVE •  To assess the significance of onabotulinumtoxinA (onabotA) intravesical administration in blocking autonomic dysreflexia (AD) response induced by cystometrogram (CMG) after T4 spinal cord transection (SCT). MATERIALS AND METHODS •  Female rats were stratified into three groups: a sham group; a SCT‐only group; and a SCT with onabotA treatment group. Each group was further subdivided into two subgroups: AD assessment, or nerve growth factor (NGF) assessment via enzyme‐linked immunosorbent assay (ELISA). •  Three weeks after T4‐SCT, all groups were assessed. Arterial pressure and heart rate were measured during and after CMG. •  NGF was also extracted from the bladder and the dorsal root ganglia (DRG) of the T4 root and quantified by ELISA. In the onabotA‐treated group, 48 h before assessment, onabotA (1 mL, 20 U/mL in saline) was given using a urethral tube and was left indwelling for 30 min. •  Univariate anova was used to analyse the data and statistical significance was set at P < 0.05. RESULTS •  The maximum voiding pressure and the number of uninhibited contractions were significantly lower in the group treated with intravesical onabotA than in the SCT‐only group. •  Intravesical onabotA significantly blocked the dysreflexia response (high arterial pressure with bradycardia) induced by CMG after SCT. •  Intravesical onabotA also significantly lowered NGF concentrations in the bladder and the T4 DRG segment. CONCLUSIONS •  The results of the present study showed that intravesical onabotA controls neurogenic detrusor overactivity and AD after SCT. •  The findings shed light on the potential benefits of intravesical onabotA treatment in patients with spinal cord injury, and also provide a novel mechanism for the control of AD via a minimally invasive treatment modality.