Chronic pudendal neuromodulation using an implantable microstimulator improves voiding function in diabetic rats

Hsieh, Tsung‐Hsun; Lin, Yin Shiou; Chen, Shih Ching; Peng, Chih Wei

doi:10.1088/1741-2560/13/4/046001

Cited by 9 publications

(10 citation statements)

References 44 publications

(70 reference statements)

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“…The middle segment of the nerve tissue was cut into slices with 2 μm thickness. We used hematoxylin and eosin staining (Hsieh et al, 2016 ), the light microscope (Leica DM 4500b) and ImageJ to measure axonal density and myelin thickness of the afferents in the sensory branch of pudendal nerve.…”

Section: Methodsmentioning

confidence: 99%

Age is associated with reduced urethral pressure and afferent activity in rat

Geramipour

Danziger

2021

Physiological Reports

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Age‐related changes in the lower urinary tract (LUT) can affect the coordination of reflexes and increase the incidence of bladder disorders in elderly. This study examines the age‐related loss of urethral signaling capability by measuring the afferent activity directly. We find that less urethral pressure develops in response to fluid flow in old rats compared to young rats and that pressure and flow evoke less urethral afferent activation. These findings are consistent with our previous study demonstrating that the urethra‐to‐bladder reflex, which is required for efficient voiding, becomes weaker with age. We measured the pudendal afferent response in young (4–7 months) and old (18–24 months) rats to fluid flow in the urethra across a range of flow rates. We used paraffin embedding and hematoxylin and eosin staining to quantify age‐related changes in the sensory branch of the pudendal nerve. Urethral afferent signaling in response to the same urethral flow rates was weaker in older animals. That is, the sensitivity of urethra afferents to flow decreased with age, and higher flow rates were required in older animals to recruit urethra afferents. There was also a reduction in the myelin thickness of pudendal afferents in old rats, which is a possible contributing factor to the sensory activity. Furthermore, the same flow rates evoked less pressure in the urethras of old animals, indicating there is an age‐related change of the urethral tissue that reduces the pressure stimulus to which these afferents respond. These results help characterize the underlying changes in LUT system with age.

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Section: Methodsmentioning

confidence: 99%

Age is associated with reduced urethral pressure and afferent activity in rat

Geramipour

Danziger

2021

Physiological Reports

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“…As previously stated, neuropathy is one of the underlying causes of diabetes related bladder dysfunction. Neuromodulation was shown to restore voiding function in several studies (Chen et al 2013 ; Hsieh et al 2016 ; Han et al 2021 ). Voiding efficacy in control animals was found about 75% while it was measured as 30.02 ± 7.89% after 8 weeks of diabetes and 19.98 ± 6.03% after 18 weeks of diabetes in STZ-induced T1DM male rats (Chen et al 2013 ).…”

Section: Emerging Pathophysiology-based Treatments Of Lutd In Diabetesmentioning

confidence: 99%

Established and emerging treatments for diabetes-associated lower urinary tract dysfunction

Erdogan

Liu

Arioglu‐Inan

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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Dysfunction of the lower urinary tract (LUT) including urinary bladder and urethra (and prostate in men) is one of the most frequent complications of diabetes and can manifest as overactive bladder, underactive bladder, urinary incontinence, and as aggravated symptoms of benign prostate hyperplasia. We have performed a selective literature search to review existing evidence on efficacy of classic medications for the treatment of LUT dysfunction in diabetic patients and animals, i.e., α1-adrenoceptor and muscarinic receptor antagonists, β3-adrenoceptor agonists, and phosphodiesterase type 5 inhibitors. Generally, these agents appear to have comparable efficacy in patients and/or animals with and without diabetes. We also review effects of antidiabetic medications on LUT function. Such studies have largely been performed in animal models. In the streptozotocin-induced models of type 1 diabetes, insulin can prevent and reverse alterations of morphology, function, and gene expression patterns in bladder and prostate. Typical medications for the treatment of type 2 diabetes have been studied less often, and the reported findings are not yet sufficient to derive robust conclusions. Thereafter, we review animal studies with emerging medications perhaps targeting diabetes-associated LUT dysfunction. Data with myoinositol, daidzein, and with compounds that target oxidative stress, inflammation, Rac1, nerve growth factor, angiotensin II receptor, serotonin receptor, adenosine receptor, and soluble guanylyl cyclase are not conclusive yet, but some hold promise as potential treatments. Finally, we review nonpharmacological interventions in diabetic bladder dysfunction. These approaches are relatively new and give promising results in preclinical studies. In conclusion, the insulin data in rodent models of type 1 diabetes suggest that diabetes-associated LUT function can be mostly or partially reversed. However, we propose that considerable additional experimental and clinical studies are needed to target diabetes itself or pathophysiological changes induced by chronic hyperglycemia for the treatment of diabetic uropathy.

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“…The VE is the ratio of the voided volume (VV) to the VT. The VV was calculated as the VT subtracted from the residual volume (RV) of saline introverted through the intravesical catheter after the final voiding contraction [15].…”

Section: Urodynamic Analysismentioning

confidence: 99%

“…The SP was defined as a quiet period flanked by two high-frequency spikes, which was further well defined as a static period sandwiched between the transformation point of high-frequency spikes into low-frequency waves and vice versa. APs are high-frequency spikes that are separated by an idle period, and an AP can also be demarcated as the period flanked by low-frequency waves transformed to high-frequency spikes and contrariwise [15].…”

Section: Urodynamic Analysismentioning

confidence: 99%

The voiding efficiency in rat models with dopaminergic brain lesions induced through unilateral and bilateral intrastriatal injections

et al. 2020

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Bladder dysfunction is a common phenomenon in Parkinson’s disease (PD) patients. A research attempt was made to analyze the voiding efficiency (VE) and bladder functions in rats with PD induced by unilateral or bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. PD rats were divided into unilateral- and bilateral-injected groups and subjected to rotation and beam walking tests. Further, the experimental rats underwent cystometric measurements for analyses of bladder dysfunction and VE. Immunohistochemical analysis was performed to analyze the dopaminergic neuron depletion on the target area. Outcomes of the rotation and beam walking tests revealed the extent of parkinsonism in the experimental rats. Urodynamic observations denoted that rats with unilateral PD exhibited a significantly decreased VE (from 68.3±3.5% to 32.7±5.8%), while rats with bilateral PD displayed a much-reduced and substantially lower level of VE of 18.3±5.1% compared to the control value and to that of rats with unilateral PD. Rats with bilateral PD showed more-extensive behavioral deficits and urodynamic changes than did rats with unilateral PD. These significant changes in motor, behavioral, bladder function and VE were due to an extensive degeneration of dopaminergic neurons in the substantia nigra region on both sides of the brain. The obtained results were substantiated with appropriate immunohistochemical results.

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Chronic pudendal neuromodulation using an implantable microstimulator improves voiding function in diabetic rats

Cited by 9 publications

References 44 publications

Age is associated with reduced urethral pressure and afferent activity in rat

Age is associated with reduced urethral pressure and afferent activity in rat

Established and emerging treatments for diabetes-associated lower urinary tract dysfunction

The voiding efficiency in rat models with dopaminergic brain lesions induced through unilateral and bilateral intrastriatal injections

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