AA

Capsaicin and Resiniferotoxin

The use of capsaicin (CAP), a vanilloid, as a topical temporary analgesic is not uncommon as evidenced by over-the-counter ointments available for purchase in local pharmacies and topical patches available for allodynia pain in Europe. Capsaicin induced localized and reversible anti-nociception results from C-fibre conduction and subsequent neuropeptide release inactivation (Dray 1992). Although C-fibers are not involved in normal voiding, neuroplastic changes to C-fiber bladder afferent growth account for injury emergent C-fiber mediated voiding reflex (i.e., spinal detrusor hyperreflexia; deGroat 1995). Resiniferatoxin (RTX) is another vanilloid which has been studied for its similar beneficial effects; however, it has less irritation to the bladder and is therefore better tolerated. By chemically reducing C-fiber bladder afferent influence with intravesical vanilloids (i.e., CAP, RTX), bladder contractility is decreased and bladder capacity is increased (Evans 2005).

Table: Capsaicin

Discussion

DeSeze et al. (1998) has provided level 1b evidence in support of the ability of CAP to improve bladder function. The authors found that 30 days after CAP instillation, compared to placebo, it was effective in decreasing 24h voiding frequency (p=0.016), decreasing 24h leakages (p=0.0008), increasing maximal cystometric capacity (p=0.01). This study offers support to other small, non-RCT studies that reported significant CAP-induced increases in bladder capacity (Das et al. 1996; Dasgupta et al. 1998). However, a small RCT cross-over study did not find differences in bladder improvement between individuals receiving CAP versus placebo (Petersen et al. 1999).

George et al. (2007) described the use of a one time instillation of CAP and reported that the “efficacy” of cystometric capacity was significant. However, when evaluating the data, it seems the significant difference was actually a significant decline in capacity at 3 hours (pre=224.6 cc, 3 hr post=139.6 cc, p=0.015) and a non-significant decline at 1 week (174.2 cc at 1 week, p=0.059). The authors claim that there was a marked, progressive and overall improvement following CAP except for leak point pressure. But the statistical results do not support this claim, and only leak volume was improved statistically at 2 weeks. Autonomic dysreflexia, a significant side effect, was reported in 2 patients following CAP. Although this study included blinded evaluations of OXY versus propantheline instillation, CAP evaluations could not be blinded and therefore, a discussion of OXY versus propantheline results was undertaken separately.

Dasgupta et al. (1998) confirmed the presence of metaplasia, dysplasia, and flat carcinoma in situ after treatment with Intravesical CAP. All biopsies were determined to be benign but some showed signs of chronic inflammation; this finding has been supported by a small cross-over RCT by Petersen et al. (1999). Dasgupta et al. (1998) reported that neither papillary nor solid invasive cancer was detected after 5 years of follow-up. Further surveillance is required up to 10 years when chemical carcinogenic morphologies typically present.

DeSeze et al. (2004) established that RTX was similarly effective in increasing bladder capacity when compared to CAP. CAP was significantly more effective at increasing urgency delay (p<0.01) but there was only a trend to greater maximum bladder capacity in favour of CAP. The increase in persistent clinical improvements due to RTX over CAP at 90 days follow-up was not statistically significant. Although there was also a statistically significant increase in suprapubic pain with CAP, it was clinically tolerable and brief (p<0.04).

Despite non-significant findings reported in a small non-RCT by Shin et al. (2006), the efficacy of RTX has been confirmed one RCT (Silva et al. 2005) and two pre-post studies (Watanabe et al. 2004; Lazzeri et al. 1998). Compared to placebo, Silva et al. (2005) found that RTX was responsible for significantly increased volume of first involuntary detrusor contraction (p=0.03), maximum cystometric capacity (p=0.02), decreased urinary frequency (p=0.01) and incontinence (p=0.03) with similar side effects as compared to placebo. Kim et al. (2003) confirmed the improvements in SCI bladder function and further investigated the effect of RTX dosing. Despite the small sample size in each dose category, maximum cystometric capacity increased by 53% and 48% for doses of 0.5 uM and 1.0 uM, respectively, by 3 weeks post-treatment. Similarly, incontinence episodes decreased by 51.9% and 52.7%, respectively.

Conclusion

There is level 1a evidence (from four RCTs and three level 4 studies; Silva et al. 2005; deSeze et al. 2004; Kim et al. 2003; deSeze et al. 1998) that the use of vanillanoid compounds such as capsaicin or resiniferatoxin increases maximum bladder capacity, and decreases urinary frequency, leakages, and pressure in neurogenic detrusor overactivity of spinal origin.

There is level 4 evidence (from one post test study; Dasgupta et al. 1998) that intravesical capsaicin instillation in bladders of individuals with SCI does not increase the rate of common bladder cancers after 5 years of use. 

  • Vanillanoid compounds such as capsaicin or resiniferatoxin increase maximum bladder capacity, and decreases urinary frequency, leakages, and pressure in neurogenic detrusor overactivity.

    Intravesical capsaicin instillation in bladders of individuals with SCI does not increase the rate of common bladder cancers after 5 years of use.