1.Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves.
Xin LIU ; Chao-Yue ZHANG ; Xiu-Yu DU ; Shan-Shan LI ; Yu-Qing WANG ; Yi ZHENG ; Han-Zhi DENG ; Xiao-Qin FANG ; Jia-Ying LI ; Zu-Qing WANG ; Shi-Fen XU ; Yi-Qun MI
Journal of Integrative Medicine 2025;23(1):46-55
OBJECTIVE:
The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.
METHODS:
Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve.
RESULTS:
Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.
CONCLUSION
Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals
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Urinary Bladder, Overactive/physiopathology*
;
Mast Cells/physiology*
;
Rats, Sprague-Dawley
;
Female
;
Acupuncture Therapy
;
Acupuncture Points
;
Rats
;
Brain/physiopathology*
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Tibial Nerve/physiopathology*
;
Acetic Acid
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Urinary Bladder/physiopathology*
2.Radiographic Position of the Electrode as a Predictor of the Outcome of InterStim Therapy.
Abdullah Ahmed GAHZI ; Mai Ahmed BANAKHAR ; Dean S ELTERMAN ; Magdy HASSOUNA
International Neurourology Journal 2017;21(4):289-294
PURPOSE: Sacral neuromodulation (SNM) therapy is indicated for some refractory urological conditions. The electrode lead position in sacral x-rays during routine follow-up may predict the outcome of SNM therapy. To determine whether the radiographic position of the electrode in the sacral foramen predicted the long-term outcome of SNM therapy. METHODS: This was a retrospective study of patients who underwent InterStim SNM at Toronto Western Hospital by 2 surgeons from July 2013 to March 2014. The position of electrodes in relation to the sacral bone was assessed on follow-up sacral x-rays. In the lateral view, we determined the location of the radio-opaque marker of the electrode relative to the inner surface of the sacrum (P3, D3, P2, D2, P1, D1, P0, and D0). In the anteroposterior view, the angle between a line through the spinous process shadow and the electrode was measured (0°–30°, 30°–60°, 60°–90°, >90°, or medial). Dissatisfied patients were defined as those who did not improve based on a voiding diary or those who needed salvage treatment after SNM. The primary endpoint was to determine whether the electrode lead position on sacral x-rays predicted the outcome of SNM therapy. RESULTS: A total of 69 patients (61 female and 8 male patients) were included, with a median age of 55 years. Forty-two of the patients (60.9%) had refractory overactive bladder, 21 (30.4%) suffered from chronic urinary retention, and 6 (8.7%) had lower urinary tract symptoms and chronic pelvic pain syndrome. The univariate analysis did not show any correlation between SNM response and the electrode position or angle. Dummy regression analysis using response to implantation as the dependent outcome variable did not show any significance for any of the predictors. CONCLUSIONS: Our study did not show a correlation between the long-term response to SNM and the electrode position on follow-up sacral x-rays. In this study, electrode lead position in sacral x-ray at follow-up was not correlated with the outcome of SNM therapy.
Electrodes*
;
Female
;
Follow-Up Studies
;
Humans
;
Lower Urinary Tract Symptoms
;
Male
;
Pelvic Pain
;
Retrospective Studies
;
Sacrum
;
Salvage Therapy
;
Surgeons
;
Urinary Bladder, Overactive
;
Urinary Incontinence
;
Urinary Retention
3.New pharmacotherapy for treating overactive bladder: mirabegron and botulinum toxin.
Journal of the Korean Medical Association 2016;59(10):795-803
Overactive bladder (OAB) is a symptom-driven condition characterized by urinary urgency with or without urinary incontinence and a common problem that can significantly affect quality of life. Drugs that prevent acetylcholine-mediated involuntary detrusor contractions are the mainstay of OAB treatment, but several alternative therapeutic options have become established treatments for OAB. Mirabegron (a β3-adrenoceptor agonist) has a different mechanism of action from antimuscarinic agents. Recently published randomized controlled trials have shown that mirabegron is an effective and safe drug for the symptomatic treatment of OAB patients. Mirabegron represents a valid option both for patients with OAB who are antimuscarinics treatment-naïve, as well as for those who are unresponsive or intolerant to antimuscarinics. Intravesical injection of botulinum toxin A is an effective treatment for OAB that is refractory to antimuscarinics. Treatment with botulinum toxin A showed clinically relevant improvement in all OAB symptoms and health-related quality of life. It was generally well tolerated by most patients, and most treatment-related complications were acceptable. However, increased risk of a larger volume of post-void residual urine was noted in several patients and the possibility of chronic catheterization requires careful evaluation before treatment. In sum, recent options for management of OAB, mirabegron and intravesical injection of botulinum toxin A, expand the treatment options for the optimal treatment of each patient.
Administration, Intravesical
;
Botulinum Toxins*
;
Catheterization
;
Catheters
;
Drug Therapy*
;
Humans
;
Muscarinic Antagonists
;
Quality of Life
;
Urinary Bladder, Overactive*
;
Urinary Incontinence
4.Efficacy and safety of onabotulinumtoxinA in treating neurogenic detrusor overactivity: a systematic review and meta-analysis.
Xin ZHOU ; Hui-Lei YAN ; Yuan-Shan CUI ; Huan-Tao ZONG ; Yong ZHANG ;
Chinese Medical Journal 2015;128(7):963-968
BACKGROUNDOnabotulinumtoxinA is widely used in treating neurogenic detrusor overactivity (NDO). We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating NDO.
METHODSWe searched the following databases: Medline, EMBASE, and the Cochrane Controlled Trials Register. All published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for the treatment of NDO were identified in the analysis. The reference lists of the retrieved studies were also investigated.
RESULTSFour publications involving a total of 807 patients were identified in the analysis, which compared onabotulinumtoxinA with placebo. The changes of the mean number of urinary incontinence per week (the standardized mean difference [SMD] = -10.91, 95% confidence intervals [CIs] = -14.18--7.63, P < 0.0001); maximum cystometric capacity (SMD = 146.09, 95% CI = 126.19-165.99, P < 0.0001) and maximum detrusor pressure (SMD = -32.65, 95% CI = -37.83--27.48, P < 0.0001) indicated that onabotulinumtoxinA was more effective than the placebo, despite the doses of onabotulinumtoxinA. Safety assessments primarily localized to the urinary tract indicated onabotulinumtoxinA were often associated with more complications. Urinary tract infections (relative risk [RR] =1.48, 95% CI = 1.20-1.81, P = 0.0002); hematuria (RR = 1.81, 95% CI = 1.00-3.24, P = 0.05) and urinary retention (RR = 5.87, 95% CI = 3.61-9.56, P < 0.0001).
CONCLUSIONSThis meta-analysis indicates that onabotulinumtoxinA to be an effective treatment for NDO with side effects primarily localized to urinary tract.
Botulinum Toxins, Type A ; adverse effects ; therapeutic use ; Humans ; Urinary Bladder, Overactive ; drug therapy
5.Urodynamic tests contribute to the choice of therapies for type-III B prostatitis.
Wei-hua LIU ; Xiao-dong JIN ; Yao-wu SU ; Liang ZHOU ; Qian-hao ZHU
National Journal of Andrology 2015;21(1):35-37
OBJECTIVETo analyze the parameters of urodynamic tests for patients with type-III B prostatitis and evaluate the significance of the results of urodynamic tests in the choice of therapies for this disease.
METHODSUrodynamic tests were performed for 87 type-III B prostatitis patients aged 22-45 (30.7 ± 8.5) years, who had moderate or severe lower urinary tract symptoms (LUTS) and failed to respond to routine therapy. Different treatments were administered according to the results of urodynamic tests followed by observation of the therapeutic effects.
RESULTSUrodynamic abnormalities were found in 70 of the 87 patients, bladder outlet obstruction in 28 (32.2%), detrusor overactivity in 25 (28.7%), bladder hyperesthesia in 18 (20.7%), low compliance in 10 (11.5%), detrusor-external urethral sphincter dyssynergia in 1 (1.1%), and impaired detrusor contractile function in 1 (1.1%). Treatments achieved obvious effectiveness in 26 cases (29.9%), effectiveness in 51 (58.6%), and no effectiveness in 10 (11.5%).
CONCLUSIONUrodynamic tests contribute significantly to the choice of therapies for type-III B prostatitis patients with moderate or severe LUTS.
Adult ; Humans ; Lower Urinary Tract Symptoms ; physiopathology ; therapy ; Male ; Middle Aged ; Prostatitis ; physiopathology ; therapy ; Urethra ; physiopathology ; Urinary Bladder Neck Obstruction ; physiopathology ; Urinary Bladder, Overactive ; physiopathology ; Urodynamics
6.NGF and HB-EGF: Potential Biomarkers that Reflect the Effects of Fesoterodine in Patients with Overactive Bladder Syndrome.
Soo Rim KIM ; Yeo Jung MOON ; Sei Kwang KIM ; Sang Wook BAI
Yonsei Medical Journal 2015;56(1):204-211
PURPOSE: To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. MATERIALS AND METHODS: This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. RESULTS: Urinary levels of NGF/Cr (OAB: 1.13+/-0.9 pg/mg; control: 0.5+/-0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73+/-6.55 pg/mg; control: 4.45+/-2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13+/-0.08 pg/mg; 16 weeks: 0.60+/-0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73+/-6.55 pg/mg; 16 weeks: 4.72+/-2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores. CONCLUSION: Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.
Adult
;
Benzhydryl Compounds/pharmacology/*therapeutic use
;
Biological Markers/urine
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Case-Control Studies
;
Creatinine/urine
;
Female
;
Heparin-binding EGF-like Growth Factor/*urine
;
Humans
;
Male
;
Middle Aged
;
Nerve Growth Factor/*urine
;
Questionnaires
;
Treatment Outcome
;
Urinary Bladder, Overactive/*drug therapy/physiopathology/*urine
;
Urodynamics
7.Drug therapy of overactive bladder - What is coming next?.
Korean Journal of Urology 2015;56(10):673-679
After the approval and introduction of mirabegron, tadalafil, and botulinum toxin A for treatment of lower urinary tract symptoms/overactive bladder, focus of interest has been on their place in therapy versus the previous gold standard, antimuscarinics. However, since these agents also have limitations there has been increasing interest in what is coming next - what is in the pipeline? Despite progress in our knowledge of different factors involved in both peripheral and central modulation of lower urinary tract dysfunction, there are few innovations in the pipe-line. Most developments concern modifications of existing principles (antimuscarinics, beta3-receptor agonists, botulinum toxin A). However, there are several new and old targets/drugs of potential interest for further development, such as the purinergic and cannabinoid systems and the different members of the transient receptor potential channel family. However, even if there seems to be good rationale for further development of these principles, further exploration of their involvement in lower urinary tract function/dysfunction is necessary.
Adrenergic beta-3 Receptor Agonists/therapeutic use
;
Botulinum Toxins, Type A/therapeutic use
;
Drug Therapy, Combination
;
Humans
;
Molecular Targeted Therapy/methods/trends
;
Muscarinic Antagonists/therapeutic use
;
Neuromuscular Agents/therapeutic use
;
Urinary Bladder, Overactive/*drug therapy
9.Efficacy of combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia with overactive bladder.
Zhong-Wei GAO ; Shi-Yong XIN ; Jian-Guo ZHANG ; Xiao-Qiang REN ; Ya-Feng SHANG ; Wei ZHANG ; Hui-Bing LI ; Fei XIAO ; Chang-Shuai SHAO
National Journal of Andrology 2014;20(3):239-243
OBJECTIVETo evaluate the efficacy and safety of the combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia (BPH) with overactive bladder (OAB).
METHODSWe randomly divided 166 patients with BPH and concomitant OAB into a mild obstruction symptom group (n = 88) and a moderate obstruction symptom group (n =78), 48 of the former group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 40 with 0. 2 mg tamsulosin; 36 of the latter group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 42 with 0. 2 mg tamsulosin, all administered once daily for 12 weeks. We obtained the International Prostate Symptom Score (IPSS), urine storage period symptom score (USPSS), voiding symptom score (VSS), Qmax, residual urine volume, OAB symptom score (OABSS) and adverse reactions, and compared them among different
RESULTSAmong the patients with mild obstruction symptoms, the combination of tamsulosin and solifenacin achieved remark-groups. able improvement in IPSS, USPSS, Qmax and OABSS as compared with the baseline (P < 0.05), but made no significant difference in the residual urine volume (P > 0. 05) , while tamsulosin improved IPSS only (P < 0.05). The combination therapy exhibited an obvious superiority over tamsulosin alone in improving IPSS (9.7 micro 3.0 vs 15.8 micro 3.3), USPSS (8. 1 micro 1.7 vs 12.3 micro 3.1), Qmax ([18.6 micro 2.3] ml/s vs [14.2 micro 2.3] ml/s ), and OABSS (5.3micro 1.3 vs 9.7 micro 2.7) (P < 0.05), but there were no obvious differences in residual urine, urine routine test results and adverse events between the two therapies ( P > 0. 05). In those with moderate obstruction symptoms, the combination therapy significantly improved IPSS, VSS, Qmax and OABSS (P < 0.05) but not the residual urine (P > 0. 05) in comparison with the baseline. The tamsulosin therapy achieved obvious improvement in IPSS, VSS, Qmax, OABSS and residual urine. The combination therapy showed a better effect than tamsulosin only in OABSS (4. 8 +/-1.5 vs 6.5 +/-2.5, P < 0.05), but no significant differences from the latter in IPSS, Qmax, VSS, routine urine test results, and adverse
CONCLUSIONCombination therapy of tamsulosin and solifenacin is obviously safe and efficacious in the treatment (P > 0.05). events of both mild and moderate BPH with concomitant OAB, and it is superior to tamsulosin alone.
Aged ; Drug Therapy, Combination ; Humans ; Male ; Middle Aged ; Prospective Studies ; Prostatic Hyperplasia ; complications ; drug therapy ; Quinuclidines ; administration & dosage ; therapeutic use ; Solifenacin Succinate ; Sulfonamides ; administration & dosage ; therapeutic use ; Tetrahydroisoquinolines ; administration & dosage ; therapeutic use ; Urinary Bladder, Overactive ; complications ; drug therapy
10.Clinical effectiveness and safety of combined therapy with alpha-blocker and an anticholinergic drug for bladder outlet obstruction with overactive bladder: a Meta-analysis of outcomes.
Bingqian LIU ; Jianhua LI ; Yikun WANG ; Yudong WU
Chinese Journal of Surgery 2014;52(5):376-380
OBJECTIVETo compare the clinical effectiveness and safety of alpha-blocker alone and combined tamsulosin with an anticholinergic drug for bladder outlet obstruction (BOO) with overactive bladder (OAB).
METHODSLiterature search was performed using PubMed, EMBASE, Ovid, Wanfang, and CNKI from inception to October 2013 for comparative studies assessing alpha-blocker alone and combined alpha-blocker with an anticholinergic drug for BOO+OAB. Data were extracted and evaluated by two reviewers independently according to the Cochrane Handbook for systematic reviews. Meta-analyses were conducted using RevMan 5.2.
RESULTSA total of 7 studies involving 3 458 patients were included for the analysis. The values of total IPSS and storage IPSS reduced significantly after treatment in combination group (RR = -0.23, 95%CI: -0.44--0.02, P = 0.03; RR = -0.69, 95%CI: -0.88--0.51, P < 0.01). There were no significant differences between the two groups in voiding IPSS and Qmax (P = 0.86 and 0.89). The incidences of dry mouth (OR = 2.53), constipation (OR = 3.74), dizziness (OR = 0.73), and urinary retention (OR = 0.26) were higher in combination group than in alpha-blocker alone group (P < 0.05). But most adverse events were mild in degree.
CONCLUSIONAlpha-blocker combined with an anticholinergic drug in the treatment of BOO+OAB was better than that of alpha-blocker alone, and was safe and well tolerated.
Adrenergic alpha-Antagonists ; therapeutic use ; Cholinergic Antagonists ; therapeutic use ; Drug Therapy, Combination ; Humans ; Sulfonamides ; therapeutic use ; Treatment Outcome ; Urinary Bladder Neck Obstruction ; drug therapy ; Urinary Bladder, Overactive ; drug therapy

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