Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful recurrent condition characterized by the discomfort of the bladder, and current treatment options have limited effectiveness. Prolotherapy is a well-known treatment that involves the injection of non-biologic solutions to reduce pain and/or promote proliferation of soft tissue, and dextrose is the most common injectate. This study investigated the effects of dextrose prolotherapy in a rat model of IC/BPS and patients with IC/BPS. We used cyclophosphamide to induce IC/BPS in rats, and intravesical instillation of 10% dextrose solution was performed. After 1 week, we conducted a urodynamic test, bladder staining, and ECM-related gene expression analysis to examine the treatment’s efficacy. We found that dextrose treatment could recover the instability of the bladder, reduce frequent urination, and improve the glycosaminoglycan layer regeneration and the bladder wall thickness along with a significant intense expression of CD44 receptors. Furthermore, we enrolled 29 IC/BPS patients with previous hyaluronic acid/Botox treatment for more than 6 months with remained unchanged condition. In this study, they received intravesical injections of 10% dextrose solution followed by assessments for up to 12 weeks. Patient characteristics and a 3-day voiding diary before treatment were recorded. Patient responses were examined using IC/BPS-related questionnaires. Moreover, expressions of growth factors and cytokines were analyzed. The results demonstrated that dextrose prolotherapy in patients with IC/BPS reduced the frequency of treatment over time, with the mean number of treatments being 3.03 ± 1.52, and significantly reduced the incidence of nocturia and questionnaire scores associated with symptoms. Dextrose prolotherapy significantly enhanced EGF level and, in contrast, reduced the level of HGF, PIGF-1, and VEGF-D after several weeks following treatment. The cytokine analysis showed that the expressions of IL-12p70 and IL-10 were significantly up-regulated after dextrose prolotherapy in IC/BPS patients. The levels of most growth factors and cytokines in IC/BPS patients had no significant difference and showed a similar tendency as time progressed when compared to healthy controls. Overall, the alteration of growth factors and cytokines exhibited safe treatment and potential stimulation of tissue remodeling. In summary, our study demonstrated that dextrose prolotherapy is a promising treatment strategy for IC/BPS disease management.
Highlights
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic bladder disorder with unclear etiology characterized with urgency, frequency, and suprapubic discomfort/pain during bladder filling (Chancellor and Yoshimura, 2004)
The rats were randomly assigned to the normal control group (n 8), cyclophosphamide-induced interstitial cystitis group (CYP) (n 8), cyclophosphamide-induced interstitial cystitis treated with physiological saline prolotherapy group (CYP + Saline) (n 8), and cyclophosphamide-induced interstitial cystitis treated with dextrose prolotherapy group (CYP + Dextrose) (n 8)
There are three hyaluronan synthases including hyaluronan synthase 1 (HAS1), hyaluronan synthase 2 (HAS2), HAS3, and hyaluronic acid receptors (CD44 and receptor for hyaluronic acidmediated motility (RHAMM)) among other interactions to regulate cell migration, proliferation, and differentiation (Kaya et al, 1997; Zaman et al, 2005; Mondalek et al, 2015; Lee et al, 2017); these are widely expressed in many cell types in the interstitial tissue
Summary
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic bladder disorder with unclear etiology characterized with urgency, frequency, and suprapubic discomfort/pain during bladder filling (Chancellor and Yoshimura, 2004). Oral pentosan polysulfate (Elmiron ) and intravesical dimethyl sulfoxide (DMSO) are two treatments approved by the United States Food and Drug Administration (FDA) to treat IC/BPS so far, these treatment show their efficacy only on limited number of patients and can cause side effects (Hanno, 1997; Augé et al, 2020). Several treatments such as hydrodistension, botulinum toxin injections, neuromodulation, and cyclosporine A instillation are commonly used in treating IC/BPS (Garzon et al, 2020); there are no reports on their long-term efficacy (Sand et al, 2008; Garzon et al, 2020)
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