Sacral Neuromodulation for Treatment-Refractory Bladder Pain Syndrome/Interstitial Cystitis

Bladder pain syndrome/interstitial cystitis (BPS/IC) has been defined as chronic pelvic pain or discomfort that is perceived to be associated with the bladder, combined with other urinary tract symptoms with a duration of at least 6 weeks, with no known cause. This definition was created by the Society for Urodynamics and Female Urology, and is used by the American Urological Association (AUA) in its diagnostic and treatment guidelines for BPS/IC that were published in 2011 and partially amended in 2015.¹

A recent study shows a prevalence of BPS/IC of 6.5% among adult women in the United States, a rate higher than previously believed.² The condition has been linked with a significant impact on quality of life as well as psychological, behavioral, sexual, and social difficulties.^3,4 Although the etiology of the disease has yet to be identified, there “is emerging evidence of neural abnormalities both peripheral and central in BPS/IC, which play an important role in pain sensitivity, urgency, and frequency symptoms,” according to the authors of a recent systematic review and meta-analysis.⁵ Dysregulated nervous system functioning “may not only maintain the perception of pain following acute injury, but also magnify pain perception in response to stimulus,” they added.

As the mechanisms underlying the pathogenesis of BPS/IC are unclear, treatment consists of the alleviation of symptoms. The AUA recommendations include 6 tiers of escalating therapies that range from more conservative approaches, such as patient education and stress management, to more invasive treatments, such as surgery and various levels of pharmacologic pain treatments. Although numerous therapies for BPS/IC are available, outcomes vary among patients, and an estimated 10% are refractory to even the most invasive approaches. “Urologists need standard treatments with reliable effectiveness and safety to handle the challenging area of refractory BPS/IC,” said Peng Wu, MD, PhD, of the department of urology at Southern Medical University in Guangzhou, China, in an interview with Clinical Pain Advisor.

Sacral neuromodulation (SNM) is a technique approved by the US Food and Drug Administration for the management of overactive bladder and non-obstructive urinary retention that may also be effective for refractory BPS/IC. “Neuromodulation is the physiological process by which the activity in one neural pathway alters preexisting activity in another pathway through synaptic interaction,” Dr Wu told Clinical Pain Advisor.

Although the mechanisms underlying the effectiveness of SNM have not yet been elucidated, it is “believed that SNM may inhibit the transmission of abnormal sensory signals to the spinal cord and brain by acting on the afferent pathway,” Dr Wu and colleagues wrote in the review article.⁵ Possible mechanisms underlying the beneficial effects of SNM on BPS/IC include the modulation of pathologic stimuli in unmyelinated C-fibers, and normalization of urinary heparin-binding epidermal growth factor-like growth factor.

Research investigating the use of SNM for refractory BPS/IC has shown mixed results and often included small samples, prompting investigators to conduct a review of relevant literature to assess the safety and efficacy of the technique in this population. Their final analysis included 17 studies (1 randomized controlled trial, 8 prospective cohort studies, and 8 retrospective case studies) comprising a total of 583 patients (89% women) who had BPS/IC for a duration of 3 to 9.1 years. Patients were followed for varying lengths of time for up to 86 months.

The results reveal a pooled success rate of 84% (95% CI, 76%-91%) as well as substantial reductions in the following outcomes:

• Pelvic pain, as assessed with scores on the visual analog scale (weighted mean difference [WMD], −3.99; 95% CI, −5.22 to −2.76; P <.00001)
• Interstitial Cystitis Problem and Symptom Index scores (WMD, −6.34; 95% CI, −9.57 to −3.10; P =.0001; and WMD, −7.17; 95% CI, −9.90 to −4.45; P <.00001, respectively)
• Daytime frequency (WMD, −7.45; 95% CI, −9.68 to −5.22; P <.00001)
• Nocturia (WMD, −3.01; 95% CI, −3.56 to −2.45; P <.00001)
• Voids per 24 hours (WMD, −9.32; 95% CI, −10.90 to −7.74; P <.00001)
• Urgency (WMD, −1.08; 95% CI, −1.79 to −0.37; P =.003)

Significant improvements in average voided volume (WMD, 95.16 mL; 95% CI, 63.64-126.69; P <.0001) were also observed. Adverse events were minimal, with the majority being transient and easily treated. “None of the complications were irreversible or life-threatening, and SNM is completely reversible,” noted Dr Wu. Pooled data show that 3% of patients experienced complications (95% CI, 0%-11%), most commonly involving pain at the implantation site, infection, lead migration, or dysfunction. Explantation of the neuromodulation implant occurred in 8% of cases (95% CI, 3%-13%), a rate that is expected to decrease with ongoing advances in the technology used in neuromodulation.

Future research in this area should focus on the etiology and pathogenesis of BPS/IC and mechanisms involved in the effectiveness of SNM in treating the disease, pointed out Dr Wu. In addition, considering the “overall low quality of included studies, further well-designed, large-volume [randomized controlled trials] are required to demonstrate and support the superiority of SNM versus other conventional treatments.”

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References

1. Hanno PM, Erickson D, Moldwin R, Faraday MM. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015; 193:1545-1553.
2. Berry SH, Elliott NM, Suttorp M, et al. Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J Urol. 2011;186:540-544.  
3. Krieger J, Stephens A, Landis JR, et al. Non-urological syndromes and severity of urological pain symptoms: baseline evaluation of the National Institutes of Health Multidisciplinary Approach to Pelvic Pain Study. J Urol. 2013;189:E181.
4. Baranowski AP. Chronic pelvic pain. Best Pract Res Clin Gastroenterol. 2009;23:593-610.
5. Wang J, Chen Y, Chen J, Zhang G, Wu P. Sacral neuromodulation for refractory bladder pain syndrome/interstitial cystitis: a global systematic review and meta-analysis. Sci Rep. 2017;7:11031.