The role of capsaicin‐sensitive afferents in autonomic dysreflexia in patients with spinal cord injury

Abstract

recurrence of DH. Urodynamic variables assessed were maximum cystometric capacity (MCC), maximum amplitude of uninhibited detrusor contraction (UICmax), the bladder capacity at 40 cmH 2 O detrusor pressure (C dp40 ) and a systolic BP of >140 mmHg or diastolic BP of >90 mmHg (C HT ). RESULTSThere was an increase in BP and a decrease in heart rate in all patients during bladder filling before capsaicin treatment. Instillation of capsaicin produced a significant increase in both systolic and diastolic BP and a significant decrease in heart rate. The maximum cardiovascular effects were at 5-10 min after instillation and gradually returned to baseline within 40 min. The vehicle had negligible effects on either BP or heart rate. After capsaicin treatment, the responses of BP and heart rate to bladder distension were significantly reduced. Both serum catecholamine values and the blood ethanol concentration remained within normal limits. The mean (range) follow-up after the first treatment was 15 (6-30) months. One month after treatment all seven patients became continent and their episodes of AD became negligible and well tolerable between catheterizations (for 3-4 h); the effects lasted for ≥ 3 months in all. MCC was significantly increased at 4 weeks and 3 months, and UICmax significantly decreased at 4 weeks after treatment. Both mean C dp40 and C HT increased 1 week, 1 and 3 months after treatment. Two patients received a second instillation, and have been continent with no symptomatic AD for 6 and 24 months. The remaining five patients have been continent with no symptomatic AD for 6-12 months. CONCLUSIONThese results indicate that intravesical capsaicin, but not the vehicle, acutely triggers AD in patients with SCI, suggesting involvement of bladder capsaicin-sensitive afferents in AD in these patients. The results also suggest that intravesical capsaicin may be a promising therapy for both AD and DH in such patients. Further long-term follow-up studies are needed to evaluate the duration of its effect. KEYWORDS autonomic dysreflexia, capsaicin, detrusor hyper-reflexia, spinal cord injury OBJECTIVESTo determine whether capsaicin-sensitive nerves in the bladder form the afferent limb involved in autonomic dysreflexia (AD) in patients with spinal cord injury (SCI). PATIENTS AND METHODSSeven men with SCI (five cervical cord, two thoracic cord) with AD and detrusor hyperreflexia (DH) were enrolled. Under general anaesthesia, capsaicin solution (100 mL of 2 mmol/L in 10% ethanol) was instilled in the bladder and retained for 30 min. The patients were assessed by medium-fill cystometry (CMG) just before and 50 min after the capsaicin treatment. Intra-arterial blood pressure (BP) and heart rate were monitored continuously throughout the procedure; 10% ethanol was instilled before capsaicin treatment in four patients as a control. Serum catecholamines were measured during bladder filling and capsaicin treatment, and the blood ethanol concentration also measured after instillation in all patients. The CMG with concomitant...

Effects of liposome-based local suppression of nerve growth factor in the bladder on autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury

“…Intravesical instillation with capsaicin, but not vehicle instillation, acutely worsened AD induced by bladder distention, but, one month later, it reduced bladder-related AD and urinary incontinence, suggesting that capsaicin-sensitive bladder afferents are involved in bladder-related AD (Igawa et al, 2003). A recent open-label clinical trial revealed that intradetrusor injections of onabotulinumtoxin-A decreased the severity and frequency of AD during urodynamics and during bladder-related events, and improved quality of life in patients with SCI (Fougere et al, 2016).…”

Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor overactivity: A double blind controlled randomized study

“…In previous studies using capsaicin diluted in 30% ethanol, short term side e¡ects, including supra-pubic pain, worsened symptoms of overactive bladder, facial £ush and haematuria were reported by about 90% of the patients within the ¢rst 3 weeks following vesical instillation [Fowler et al, 1992[Fowler et al, , 2000Geirsson et al, 1995;Das et al, 1996;de Ridder et al, 1996de Ridder et al, , 1997Cruz et al, 1997;de Se' ze et al, 1998de Se' ze et al, , 1999Lazzeri et al, 1998, Soontrapa et al, 2003. Some of these side e¡ects (immediate pain and other, adverse drug reactions) are probably mainly due to the pharmacological action of capsaicin in the bladder wall [Pandita et al, 1997;Igawa et al, 2003]. Bladder e¡ects of alcoholic solvent have been involved in others, such as haematuria, worsening of irritative symptoms and lasting pelvic pain [de Se' ze et al, 1998;Wiart et al, 1998].…”

Early capsaicin intervention for neurogenic bladder in a rat model of spinal cord injury

“…The benefits of this early blockade of C-fiber afferents could be the prevention of urinary incontinence and possibly the late onset damage to the upper urinary tract. Moreover, recent evidence in humans suggested that bladder afferents susceptible to capsaicin desensitization play a role in the development of autonomic dysreflexia in spinal cord injured patients (5). Autonomic dysreflexia is a medical emergency that can result in serious consequences such as a cerebral vascular accident.…”