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Intravesical Capsaicin

Capsaicin is an extract from red pepper and exerts a selective action on certain sensory nerves, most notably those involved in reflex contractions of the bladder after spinal cord injury.

 

Table 5: Capsaicin

Author Year; Country
Score
Research Design
Sample Size
MethodsOutcome
Kim et al. 2003;

USA

PEDro=9

RCT

N=36

Population: 22 males, 14 females, neurologically impaired patients (20 SCI, 7 multiple sclerosis, and 9 others) with urodynamically verified detrusor hyperreflexia.

Treatment: Randomized double blind, placebo-controlled trial. Intravesical instillation of Resiniferatoxin (RTX) 0.005, 0.025, 0.05, 0.10, 0.2, 0.5, or 1.0 microM of RTX (n=4 each group) or placebo (n=8).

Outcome Measures: incontinence episodes, bladder capacity.

1.    No statistical significance due to small sample sizes.

2.    Intravesical RTX administration was well tolerated. This patient group was refractory to all previous oral pharmacologic therapy, yet some patients responded with improvement in bladder capacity and continence function shortly after RTX administration.

3.    In some cases, mean cystometric capacity increased up to 500% over baseline.

4.    Incontinence episodes decreased by over 50% for the 2 highest doses.

5.    No data available on long term effect of RXT on AD.

Effect Sizes: Forest plot of standardized mean differences (SMD ± 95%C.I.) as calculated from pre- to post-intervention data and pre-intervention to retention/follow-up data

Giannantoni et al. 2002;

Italy

PEDro=6

RCT

N=23

Population: Refractory detrusor hyperreflexia.

Treatment: Randomized two treatments

a) single dose of 2 mM. capsaicin in 30 ml ethanol plus 70 ml 0.9% sodium chloride  OR

b) 100 mM. resiniferatoxin in 100 ml 0.9% sodium chloride.

Outcome Measures: Urodynamics, frequency of daily catheterizations, incontinence episodes and side effects.

1.    Capsaicin group showed no significant urodynamic or clinical improvements at 30 and 60 days.

2.    Resiniferatoxin group demonstrated significant urodynamic improvement at 30 and 60 days.

3.    Most patients receiving capsaicin, but none receiving resiniferatoxin developed AD, limb spasms, suprapubic discomfort and hematuria.

Effect Sizes: Forest plot of standardized mean differences (SMD ± 95%C.I.) as calculated from pre- to post-intervention data

Igawa et al. 2003; Japan

Pre-post

N=7

Population: 5 subjects with cervical injuries and 2 subjects with thoracic injuries.

Treatment: bladder instillation with capsaicin solution under general anesthesia.

Outcome Measures: blood pressure, heart rate, serum catecholamines, blood ethanol concentration.

1.  Capsaicin attenuated elevated BP secondary to bladder distention (empty or full) post-treatment.

2.  In all individuals, episodes of AD become negligible and well tolerated > 3 months.

 

Discussion

One RCT (n=23) (Giannantoni et al. 2002) and one pre-post study (n=7) (Igawa et al. 2003) evaluated the effect of capsaicin. Capsaicin exerts a selective action on those sensory nerves involved in reflex contractions of the bladder after SCI. In their pre-post study, Igawa et al. (2003) demonstrated that intravesical capsaicin decreased episodes of AD in patients with SCI during catheterization, thereby suggesting the therapeutic potential of intravesical capsaicin for both AD and detrusor hyperreflexia in SCI patients (Igawa et al. 2003). Giannantoni et al. (2002) in a high quality RCT (PEDro=6) used an analogue of capsaicin (resiniferatoxin RXT) that is more than 1,000 times more potent in desensitizing C-fiber bladder afferents and found reduced episodes of AD (Giannantoni et al. 2002). In addition, investigators found that intravesical administration of resiniferatoxin was superior to that of intravesical capsaicin in terms of urodynamic results and clinical benefits in SCI patients within 60 days of treatment and did not cause the inflammatory side effects associated with capsaicin. Long-term effects of capsaicin or resiniferatoxin on AD, however, have not been evaluated.

[su_spoiler title=”Effect Size Forest Plots of RCTs with Available Data” style=”fancy”][su_row]Click on the image to enlarge[/su_row]
[su_lightbox type=”image” src=”/wp-content/uploads/Forest_AD_Giannantoni_2002.gif”][image_with_animation image_url=”/wp-content/uploads/Forest_AD_Giannantoni_2002.gif” alt=”Effect size SMD forest plot for Giannantoni et al. 2002, capsaicin vs. resiniferatoxin”][/su_lightbox]

[su_lightbox type=”image” src=”/wp-content/uploads/Forest_AD_Kim_2003.gif”][image_with_animation image_url=”/wp-content/uploads/Forest_AD_Kim_2003.gif” alt=”Effect size SMD forest plot for Kim et al. 2003, resiniferatoxin”][/su_lightbox]
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Conclusion

There is level 4 evidence (from 1 pre-post study) (Igawa et el. 2003) that intravesical capsaicin is effective for reducing episodes of AD in SCI.

There is level 1 evidence (from 2 RCTs) (Kim et al. 2003; Giannantoni et al. 2002) that intravesical resiniferatoxin is effective for reducing episodes of AD in patients with SCI.

There is level 1 evidence (from 1 RCT) (Giannantoni et al. 2002) that intravesical resiniferatoxin is more effective than intravesical capsaicin.

  • Capsaicin and its analogue, resiniferatoxin, are effective in reducing the episodes of AD in patients with SCI.