ABSTRACT: We explored capsaicin pretreatment, prior to spinal trauma, as a method to prevent the development of neurogenic detrusor overactivity (NDO) and urethral-bladder dyssynergia reflex after spinal cord injury (SCI). In addition, the duration of effect of capsaicin therapy on NDO in a rat model of SCI was investigated. Two sets of experiments were performed on female Sprague Dawley rats transected at the T9-T10 spinal level. First, SCI rats received capsaicin (125 mg/kg s.q.) 3-4 days before and 4-5 days after SCI. Cystometrograms (CMG) was performed 4 weeks after injury. In the second set of experiments, serial CMG in the same SCI animal was performed after one time injection of capsaicin (125 mg/kg s.q.) 4 weeks after spinalization. There were no differences in intercontraction intervals, voiding efficiency, or voiding pressure between the capsaicin pretreated and control SCI rats. However, the number of uninhibited detrusor contractions decreased 4 weeks after injury. We found that a single dose of capsaicin suppressed uninhibited detrusor contractions for 34 days in the chronic SCI animals. Early therapy with capsaicin was able to prevent/reduce detrusor hyperreflexia in spinal cord injured animals 4 weeks after injury. Early vanilloid therapy may prevent development of urologic sequelae after SCI.
Biomedical Research 11/2007; 28(5):255-9. · 1.15 Impact Factor
ABSTRACT: To create a model of peripheral neuropathy and explore the potential of using muscle-derived cells (MDCs) to facilitate the regeneration of autonomic nerves and improve bladder function. Damage to the peripheral nerves that innervate the bladder from radical pelvic surgery is refractory to the currently available treatments.
Rat MDCs were isolated from the gastrocnemius muscle using the preplate technique. The unilateral pelvic nerve was cut in female Sprague-Dawley rats. Three experimental groups were included: control (n = 5); unilateral pelvic nerve transected with sham injection (n = 5); and unilateral pelvic nerve transected with injection of MDC (3 x 10(5) cells/site; n = 5). Two weeks after injection, the intravesical pressures were measured during electrical stimulation of the proximal transected preganglionic nerve. The contralateral major pelvic ganglion was excised to ensure that any observed bladder activity was due exclusively to inputs on the unilateral side. The rats were killed, the experimental side major pelvic ganglion was removed, and enkephalin immunoreactivity was counted.
After unilateral pelvic nerve transection, no change occurred in bladder weight or capacity or postvoid residual urine volume. The maximal intravesical pressures for the control, sham, and MDC groups, after the contralateral pelvis had been cut, was 31.7 +/- 10.3, 9.6 +/- 4.5, and 15.2 +/- 7.7 cm H2O, respectively (P <0.05). After transecting the preganglionic pelvic nerve, the intensity of pericellular enkephalin immunoreactivity varicosities was significantly decreased in the sham group but unchanged in the MDC group compared with the control group.
MDCs can promote peripheral autonomic nerve regeneration. The morphologic changes correlated with the functional neurologic recovery effect of MDCs. The underlying neurologic recovery mechanisms of MDCs need to be exploited.
Urology 06/2005; 65(6):1249-53. · 2.43 Impact Factor
ABSTRACT: Resiniferatoxin (RTX) is an analogue of capsaicin with more than 1,000 times its potency in desensitizing C-fiber bladder afferent neurons. This study investigated the safety and efficacy of intravesical RTX in patients with refractory detrusor hyperreflexia (DH).
Thirty-six (22 males, 14 females) neurologically impaired patients (20 spinal cord injury, 7 multiple sclerosis, 9 other neurologic diseases) with urodynamically verified DH and intractable urinary symptoms despite previous anticholinergic drug use were treated prospectively with intravesical RTX using dose escalation in a double-blind fashion at 4 centers. Patients received a single instillation of 100 mL of placebo (n = 8 patients) or 0.005, 0.025, 0.05, 0.10, 0.2, 0.5, or 1.0 microM of RTX (n = 4 each group). A visual analog pain scale (VAPS) (0-10; 10 = highest level of pain) was used to quantify discomfort of application. Treatment effect was monitored using a bladder diary and cystometric bladder capacity at weeks 1, 3, 6, and 12 posttreatment.
Mean VAPS scores revealed minimal to mild discomfort with values of 2.85 and 2.28 for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. Due to the small sample size, there were no statistically significant changes in mean cystometric capacity (MCC) or incontinence episodes in each treatment dose group. However, at 3 weeks, MCC increased by 53% and 48% for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. Patients in the 0.5-microM and 1.0-microM groups with MCC < 300 mL at baseline showed greater improvements in MCC at 120.5% and 48%, respectively. In some patients, MCC increased up to 500% over baseline, despite a low RTX dose. Incontinence episodes decreased by 51.9% and 52.7% for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. There were no long-term complications.
Intravesical RTX administration, in general, is a well-tolerated new therapy for DH. This patient group was refractory to all previous oral pharmacologic therapy, yet some patients responded with significant improvement in bladder capacity and continence function shortly after RTX administration. Patients at risk for autonomic dysreflexia require careful monitoring during RTX therapy.
The journal of spinal cord medicine 01/2003; 26(4):358-63. · 2.11 Impact Factor