title: The role of capsaicin-sensitive afferents in autonomic dysreflexia in patients with spinal cord injury.
abstract: OBJECTIVE
  To determine whether capsaicin-sensitive nerves in the bladder form the afferent limb involved in autonomic dysreflexia (AD) in patients with spinal cord injury (SCI).
  
  
  METHODS
  Seven men with SCI (five cervical cord, two thoracic cord) with AD and detrusor hyper-reflexia (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 monitoring of BP and heart rate was repeated 1 week, 1, 3, 6, 12 and 24 months after instillation. In two patients the instillations were repeated 5 and 12 months after the first because of recurrence of DH. Urodynamic variables assessed were maximum cystometric capacity (MCC), maximum amplitude of uninhibited detrusor contraction (UICmax), the bladder capacity at 40 cmH2O detrusor pressure (Cdp40) and a systolic BP of> 140 mmHg or diastolic BP of> 90 mmHg (C(HT)).
  
  
  RESULTS
  There 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 >or= 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 Cdp40 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan. yxigawa@hsp.md.shinshu-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Igawa
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.forename: H
authors.initials: H
authors.lastname: Mizusawa
authors.forename: S
authors.initials: S
authors.lastname: Seki
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: O
authors.initials: O
authors.lastname: Ishizuka
authors.forename: O
authors.initials: O
authors.lastname: Nishizawa
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D020211:Autonomic Dysreflexia / Q000209:etiology*; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D002574:Cervical Vertebrae; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D013119:Spinal Cord Injuries / Q000150:complications*; D013904:Thoracic Vertebrae; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation*
chemical_list: D002211:Capsaicin