A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome

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...

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Main Authors: Chin-Li Chen, Chien-Chang Kao, Ming-Hsin Yang, Gang-Yi Fan, Juin-Hong Cherng, Chih-Wei Tsao, Sheng-Tang Wu, Tai-Lung Cha, En Meng
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.755615/full
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author Chin-Li Chen
Chien-Chang Kao
Ming-Hsin Yang
Gang-Yi Fan
Juin-Hong Cherng
Juin-Hong Cherng
Chih-Wei Tsao
Sheng-Tang Wu
Tai-Lung Cha
En Meng
En Meng
author_facet Chin-Li Chen
Chien-Chang Kao
Ming-Hsin Yang
Gang-Yi Fan
Juin-Hong Cherng
Juin-Hong Cherng
Chih-Wei Tsao
Sheng-Tang Wu
Tai-Lung Cha
En Meng
En Meng
author_sort Chin-Li Chen
collection DOAJ
description 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.
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spelling doaj.art-1903424590564b1082a0ccfbc4d32ed82022-12-21T18:12:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-12-011210.3389/fphar.2021.755615755615A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain SyndromeChin-Li Chen0Chien-Chang Kao1Ming-Hsin Yang2Gang-Yi Fan3Juin-Hong Cherng4Juin-Hong Cherng5Chih-Wei Tsao6Sheng-Tang Wu7Tai-Lung Cha8En Meng9En Meng10Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanGraduate Institute of Life Sciences, National Defense Medical Center, Taipei, TaiwanDepartment and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei, TaiwanDivision of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDepartment and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, TaiwanInterstitial 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.755615/fullbladder pain syndromeinterstitial cystitishyaluronic acid receptordextrose prolotherapyimmune systeminflammation
spellingShingle Chin-Li Chen
Chien-Chang Kao
Ming-Hsin Yang
Gang-Yi Fan
Juin-Hong Cherng
Juin-Hong Cherng
Chih-Wei Tsao
Sheng-Tang Wu
Tai-Lung Cha
En Meng
En Meng
A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome
Frontiers in Pharmacology
bladder pain syndrome
interstitial cystitis
hyaluronic acid receptor
dextrose prolotherapy
immune system
inflammation
title A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome
title_full A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome
title_fullStr A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome
title_full_unstemmed A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome
title_short A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome
title_sort novel intravesical dextrose injection improves lower urinary tract symptoms on interstitial cystitis bladder pain syndrome
topic bladder pain syndrome
interstitial cystitis
hyaluronic acid receptor
dextrose prolotherapy
immune system
inflammation
url https://www.frontiersin.org/articles/10.3389/fphar.2021.755615/full
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