Interstitial cystitis/bladder pain syndrome is a poorly understood chronic pain condition. While patients experience chronic pain in their bladders and changes to their urinary habits, they also commonly experience widespread pain and issues beyond their bladder. The cause(s) of these symptoms is not well understood. Our research found evidence that patients with interstitial cystitis commonly have damage/thinning to the nerves in their skin, which is associated with being chronically fatigued. This finding may explain some of the widespread symptoms these patients experience.

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease that, based on the variable efficacy observed with most therapeutic options, is difficult to treat effectively. A more targeted patient selection process for current and emerging therapeutic options would likely help to improve outcomes. This narrative review explores small fiber polyneuropathy (SFPN) in IC/BPS as part of a larger widespread pain phenotype and as a potential therapeutic target. Because SFPN is becoming increasingly implicated in polysyndromic pain disorders (e.g., IC/BPS, chronic pelvic pain, and fibromyalgia) in which immune dysregulation is a suspected pathophysiologic etiology, continued consideration should be given to immunomodulatory therapies such as intravenous immunoglobulin (IVIg). Moreover, since the small fibers affected in SFPN continue to grow even as people age, targeted treatment may prevent further destruction and provide long-term benefits as the fibers are given time to repair. In addition to therapeutic potential, having a definitive SFPN diagnosis may provide psychological benefit in a patient population for which symptoms have historically been attributed to negative psychological factors. Finally, based on emerging data in this area, we propose consideration be given to include SFPN testing in the work-up of patients with IC/BPS that are refractory to treatments or have multiple comorbid pain syndromes since it may be an indicator of the need for alternative therapies. We believe that SFPN will play an increasingly larger role in the clinical evaluation and management of polysyndromic pain disorders, including IC/BPS.

METHODS: Female Wistar rats were used and divided into sham control, WAS and WAS with OND treatment groups. The WAS with OND rats were treated with NGF antisense OND on the day before the first WAS session. After 1-hour WAS or sham sessions once daily for 10 days, the rats were evaluated by cystometry or pain behavior measurements followed by bladder histology. In another set of animals without functional evaluation, the bladder was harvested for molecular studies.RESULTS: Rats exposed to 10-days WAS showed shortened inter-contraction intervals (ICI) and increased pain behaviors, compared to control rats, which were improved with OND treatment (Fig 1-a,b,c). Protein assay showed increased NGF levels in the bladder mucosa in WAS rats, which were decreased by OND treatment (Fig 1-d). RT-PCR showed increases of TRPV1 and TRPA1 and a decrease in Cx43 in the bladder mucosa of WAS rats compared to control rats, which were improved in WAS rats treated with OND (Fig 1-e). Bladder histology revealed urothelial exfoliation in WAS rats, which was recovered with OND treatment (Fig 1-f,g).CONCLUSIONS: Psychological stress induced by WAS elicited bladder hypersensitivity, which was improved by NGF antisense OND treatment. Thus, liposome-based local suppression of upregulated NGF in the bladder could be an effective therapeutic modality for bladder overactivity and enhanced pain sensation induced by psychological stress.