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ABSTRACT: The contribution of metabotropic glutamate receptors (mGluR) and opioid receptors to inhibition of bladder overactivity by tibial nerve stimulation (TNS) was investigated in cats under α-chloralose anesthesia using LY341495 (a group II mGluR antagonist) and naloxone (an opioid receptor antagonist). Slow infusion cystometry was used to measure the volume threshold (i.e., bladder capacity) for inducing a large bladder contraction. After measuring the bladder capacity during saline infusion, 0.25% acetic acid (AA) was infused to irritate the bladder, activate the nociceptive C-fiber bladder afferents, and induce bladder overactivity. AA significantly (P < 0.0001) reduced bladder capacity to 26.6±4.7% of saline control capacity. TNS (5 Hz, 0.2 ms) at 2 and 4 times the threshold (T) intensity for inducing an observable toe movement significantly increased bladder capacity to 62.2±8.3% at 2T (P < 0.01) and 80.8±9.2% at 4T (P = 0.0001) of saline control capacity. LY341495 (0.1-5 mg/kg, i.v.) did not change bladder overactivity, but completely suppressed the inhibition induced by TNS at a low stimulus intensity (2T) and partially suppressed the inhibition at high intensity (4T). Following administration of LY341495, naloxone (0.01 mg/kg, i.v.) completely eliminated the high intensity TNS-induced inhibition. However without LY341495 treatment a 10 times higher dose (0.1 mg/kg) of naloxone was required to completely block TNS inhibition. These results indicate that interactions between group II mGluR and opioid receptor mechanisms contribute to TNS inhibition of AA-induced bladder overactivity. Understanding neurotransmitter mechanisms underlying TNS inhibition of bladder overactivity is important for development of new treatments for bladder disorders.
AJP Regulatory Integrative and Comparative Physiology 04/2013; · 3.34 Impact Factor
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ABSTRACT: This study examined the mechanisms underlying the effects of sacral neuromodulation on reflex bladder activity in chloralose anesthetized cats. Bladder activity was recorded during cystometrograms (CMGs) or under isovolumetric conditions. S1-S3 dorsal (DRT) or ventral root (VRT) were electrically stimulated at a range of frequencies (1-30 Hz) and at intensities relative to threshold (0.25T-2T) for evoking anal/toe twitches. Stimulation of DRTs but not VRTs at 1T intensity and frequencies of 1-30 Hz inhibited isovolumetric rhythmic bladder contractions; 5 Hz DRT stimulation during CMGs was optimal for increasing (P<0.05) bladder capacity (BC). Stimulation at 15 Hz was ineffective and 30 Hz elicited a weaker response to S1 DRT stimulation and no response to S2 DRT stimulation. Stimulation of the S1 DRT was more effective (increase BC to 143% and 163% of control at 1T and 2T, respectively) than S2 DRT stimulation (increase BC to 126% and 146% of control). Bilateral transection of the hypogastric or pudendal nerves did not change the inhibitory effect induced by S1 DRT stimulation. Repeated stimulation of S1 and S2 DRTs during multiple CMGs elicited a significant (P<0.05) increase in BC (to 155±13% of control) that persisted after termination of the stimulation. These results in cats suggest that the inhibition of reflex bladder activity by sacral neuromodulation occurs primarily in the central nervous system by inhibiting the ascending or descending pathways of the spinobulbospinal micturition reflex.
AJP Renal Physiology 01/2013; · 4.42 Impact Factor
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ABSTRACT: PURPOSE: We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity. MATERIALS AND METHODS: Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition. RESULTS: Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p <0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p <0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p >0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p <0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment. CONCLUSIONS: This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects.
The Journal of urology 10/2012; · 4.02 Impact Factor
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ABSTRACT: PURPOSE: To determine the role of opioid and metabotropic glutamate 5 receptors (mGluR5) in pudendal inhibition of bladder overactivity. MATERIALS AND METHODS: Cystometrograms (CMGs) were performed in 11 cats underα-chloralose anesthesia by slowly infusing the bladder with saline or 0.25% acetic acid (AA). Pudendal nerve stimulation at intensities of multiple times the threshold (T) to induce observable anal twitching was applied during CMGs to inhibit the bladder overactivity induced by AA irritation. Naloxone (0.1, 0.3, and 1 mg/kg, i.v.) was administered to block opioid receptors followed by MTEP (3 and 10 mg/kg, i.v.) administration to block mGluR5 receptors. After each dose of drug, pudendal inhibition of bladder overactivity was examined during CMGs. RESULTS: AA irritated the bladder, induced bladder overactivity, and significantly (P<0.0001) reduced bladder capacity to 23.6±2.7%% of saline control capacity. Pudendal nerve stimulation at 1-1.5T and 4T suppressed bladder overactivity and significantly increased the capacity to 57.5±8.1% (P=0.0005) and 106±15% (P=0.0002), respectively, of the saline control capacity. Naloxone had no effect on pudendal inhibition, but MTEP eliminated the inhibition induced by low intensity stimulation and significantly (P<0.05) reduced the inhibition induced by high intensity stimulation. Neither naloxone or MTEP altered baseline bladder overactivity. CONCLUSION: Opioid receptors are not involved in pudendal inhibition of bladder overactivity, but mGluR5 receptors are partially involved. Understanding neurotransmitter mechanisms could improve the efficacy of neuromodulation therapy for overactive bladder (OAB) treatment, and identify molecular targets for development of new drugs for treating OAB.
The Journal of urology 09/2012; · 4.02 Impact Factor
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ABSTRACT: Key points Activation of afferents in the posterior femoral cutaneous nerve (PFCN) can reflexively induce efferent firing in the pudendal nerve and pudendal afferent firing via a motor-sensory coupling. Activation of pudendal afferent nerves can inhibit the micturition reflex, suggesting PFCN stimulation might also inhibit the micturition reflex. This study discovered a somato-bladder inhibitory reflex elicited by electrical or tactile stimulation of cutaneous afferents in the PFCN, but excluded the involvement of pudendal nerves. This PFCN-bladder inhibitory reflex could be utilized to develop new neuromodulation therapies for lower urinary tract disorders.
The Journal of Physiology 08/2012; 590(Pt 19):4945-55. · 4.72 Impact Factor
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ABSTRACT: We examined the role of opioid receptors in the inhibition of bladder overactivity induced by electrical stimulation of the foot.
Experiments were done in 6 cats under α-chloralose anesthesia when the bladder was infused with saline or 0.25% acetic acid. Naloxone (1 mg/kg intravenously) was administered to block opioid receptors. To modulate reflex bladder activity electrical stimulation (5 Hz, 0.2 millisecond pulse width) was applied to the foot via skin surface electrodes at intensities of multiple times the threshold needed to induce observable toe movement.
Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE 25.3% ± 5.9% that of saline control capacity (p = 0.0001). Foot stimulation at 4T suppressed acetic acid induced bladder overactivity and significantly increased bladder capacity to 47.1% ± 5.9% of control (p = 0.0007). Naloxone did not significantly change bladder capacity during acetic acid irritation but it completely eliminated the inhibition of bladder overactivity induced by foot stimulation.
Results indicate that opioid receptors have an important role in foot afferent inhibition of bladder overactivity. This raises the possibility that opioid receptors might be used as a pharmacological target to enhance the efficacy of foot stimulation for inhibiting bladder overactivity.
The Journal of urology 07/2012; 188(3):1012-6. · 4.02 Impact Factor
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ABSTRACT: To determine if intermittent stimulation of the pudendal nerve using a transcutaneous stimulation method can inhibit reflex bladder activity. Intermittent stimulation consumes less electrical power than continuous stimulation, requiring a smaller battery and reducing the size of the stimulator for neuromodulation therapy.
A non-invasive stimulation method employing a transdermal amplitude-modulated signal (TAMS) was used in 18 α-chloralose anesthetized cats to stimulate the pudendal nerve via electrodes attached to the skin surface. Intermittent stimulation of different duty cycles was applied during repeated cystometrograms (CMGs) to inhibit reflex bladder activity. The bladder capacity measured during each CMG was used to indicate the inhibitory effect induced by the stimulation.
Continuous stimulation maximally increased bladder capacity to 172.6 ± 15% of the control capacity, while intermittent stimulation at the duty cycles of 30/30, 5/5, and 1/1 ("on/off" in seconds) significantly (P < 0.05) increased bladder capacity to 132 ± 7.5%, 154.2 ± 20%, and 165.5 ± 28%, respectively. The inhibitory effect was gradually reduced as the "on/off" ratio was decreased.
This pre-clinical study indicated that intermittent stimulation of the pudendal nerve could be as effective as continuous stimulation to inhibit reflex bladder activity. These results are useful for the design and development of new stimulator technology to treat overactive bladder, and are also important for understanding pudendal neuromodulation therapy.
Neurourology and Urodynamics 04/2012; 31(7):1181-4. · 2.96 Impact Factor
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ABSTRACT: Our recent study in cats revealed that inhibition of bladder overactivity by tibial nerve stimulation (TNS) depends on the activation of opioid receptors. TNS is a minimally invasive treatment for overactive bladder (OAB), but its efficacy is low. Tramadol (an opioid receptor agonist) is effective in treating OAB but elicits significant adverse effects. This study was to determine if a low dose of tramadol (expected to produce fewer adverse effects) can enhance the TNS inhibition of bladder overactivity. Bladder overactivity was induced in α-chloralose-anesthetized cats by an intravesical infusion of 0.25% acetic acid (AA) during repeated cystometrograms (CMGs). TNS (5 Hz) at two to four times the threshold intensity for inducing toe movement was applied during CMGs before and after tramadol (0.3-7 mg/kg iv) to examine the interaction between the two treatments. AA irritation significantly reduced bladder capacity to 24.8 ± 3.3% of the capacity measured during saline infusion. TNS alone reversibly inhibited bladder overactivity and significantly increased bladder capacity to 50-60% of the saline control capacity. Tramadol administered alone in low doses (0.3-1 mg/kg) did not significantly change bladder capacity, whereas larger doses (3-7 mg/kg) increased bladder capacity (50-60%). TNS in combination with tramadol (3-7 mg/kg) completely reversed the effect of AA. Tramadol also unmasked a prolonged (>2 h) TNS inhibition of bladder overactivity that persisted after termination of the stimulation. The results suggest a novel treatment strategy for OAB by combining tibial neuromodulation with a low dose of tramadol, which is minimally invasive with a potentially high efficacy and fewer adverse effects.
AJP Renal Physiology 04/2012; 302(12):F1576-82. · 4.42 Impact Factor
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ABSTRACT: Naloxone (an opioid receptor antagonist) was used to examine the role of opioid mechanisms in bladder reflexes and in somatic afferent inhibition of these reflexes by tibial nerve stimulation (TNS). Experiments were conducted in α-chloralose-anesthetized cats when the bladder was infused with saline or 0.25% acetic acid (AA). The bladder volume was measured at the first large-amplitude (>30 cmH(2)O) contraction during a cystometrogram and termed "estimated bladder capacity" (EBC). AA irritated the bladder, induced bladder overactivity, and significantly (P < 0.0001) reduced EBC to 14.3 ± 1.9% of the saline control. TNS (5 Hz, 0.2 ms) at 4 and 8 times the threshold (T) intensity for inducing an observable toe movement suppressed AA-induced bladder overactivity and significantly increased EBC to 41.5 ± 9.9% (4T, P < 0.05) and 46.1 ± 7.9% (8T, P < 0.01) of the saline control. Naloxone (1 mg/kg iv) completely eliminated TNS inhibition of bladder overactivity. Naloxone (0.001-1 mg/kg iv) did not change EBC during AA irritation. However, during saline infusion naloxone (1 mg/kg iv) significantly (P < 0.01) reduced EBC to 66.5 ± 8.1% of the control EBC. During saline infusion, TNS induced an acute increase in EBC and an increase that persisted following the stimulation. Naloxone (1 mg/kg) did not alter either type of inhibition. However, naloxone administered during the poststimulation inhibition decreased EBC. These results indicate that opioid receptors have different roles in modulation of nociceptive and nonnociceptive bladder reflexes and in somatic afferent inhibition of these reflexes, raising the possibility that opioid receptors may be a target for pharmacological treatment of lower urinary tract disorders.
AJP Renal Physiology 01/2012; 302(9):F1090-7. · 4.42 Impact Factor
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ABSTRACT: This study used MTEP, a metabotropic glutamate receptor 5 (mGluR5) antagonist, to examine the role of mGluR5 in the neural control of the urinary bladder and in the inhibition of the micturition reflex by pudendal nerve stimulation (PNS). Experiments were conducted in 11 female cats under α-chloralose anaesthesia when the bladder was infused with either saline or 0.25% acetic acid (AA). AA irritated the bladder, induced bladder overactivity and significantly (P < 0.001) reduced bladder capacity to 14.9 ± 10.3% of the saline control capacity. MTEP (0.1-50 mg kg(-1), i.v.) significantly (P < 0.05) increased bladder capacity during saline distension but not during AA irritation. However, MTEP induced a transient inhibition of isovolumetric bladder contractions under both conditions. PNS (5 Hz), which was tested at the threshold (T) intensity for inducing a complete inhibition of isovolumetric bladder contractions and at an intensity of 3-4T, suppressed AA-induced bladder overactivity and significantly increased bladder capacity to 68.0 ± 31.3% at 1T (P < 0.05) and 98.5 ± 55.3% at 3-4T (P < 0.01) of the saline control capacity. MTEP dose dependently (0.1-50 mg kg(-1), i.v.) suppressed PNS inhibition of bladder overactivity at low intensity (1T) but not at high intensity (3-4T). During saline infusion PNS significantly (P < 0.05) increased bladder capacity to 167.7 ± 27.1% at 1T and 196.0 ± 37.4% at 3-4T. These inhibitory effects were not observed after MTEP (0.1-50 mg kg(-1), i.v.) which also increased bladder capacity. These results indicate that glutamic acid has a transmitter function in bladder and somato-bladder reflex mechanisms and raise the possibility that mGluR5 may be a target for pharmacological treatment of lower urinary tract disorders.
The Journal of Physiology 12/2011; 589(Pt 23):5833-43. · 4.72 Impact Factor
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ABSTRACT: We determined whether transcutaneous electrical stimulation of somatic afferent nerves in the foot of cats would induce a post-stimulation increase in bladder capacity.
In 12 α-chloralose anesthetized cats electrical stimulation (5 Hz) was applied to the skin of the hind foot for 2, 30-minute periods via dual pad electrodes attached on the plantar and dorsal surfaces (combination 1 and 2) or at 2 sites on the plantar surface (combination 1 and 3). The post-stimulation effect was examined by repeat cystometrogram after 30-minute stimulation. In the control group of 12 cats isovolumetric contractions were allowed to continue during each 30-minute period without stimulation.
Stimulation inhibited isovolumetric rhythmic bladder contractions. Bladder capacity was not increased after the first 30-minute foot stimulation via electrodes 1 and 2 but it was significantly increased a mean ± SE of 47.5% ± 2.9% after the second 30-minute stimulation via electrodes 1 and 3. After inducing the post-stimulation effect the foot stimulation applied during cystometrograms via electrodes 1 and 2 or 1 and 3 elicited a further increase in bladder capacity (mean 23.26% ± 17.64% and 20.07% ± 18.59%, respectively).
Results show that the transcutaneous plantar electrical stimulation of somatic afferent nerves in the foot can induce a post-stimulation increase in bladder capacity, suggesting that an intermittent stimulation pattern rather than continuous stimulation might be effective as clinical application to treat overactive bladder symptoms.
The Journal of urology 11/2011; 187(1):338-43. · 4.02 Impact Factor
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ABSTRACT: • To develop a non-invasive neuromodulation method targeting the pudendal nerve.
• Bladder overactivity induced by acetic acid (AA) irritation was partially suppressed by electrical stimulation of the pudendal nerve in α-chloralose anaesthetized cats using a transdermal amplitude-modulated signal (TAMS).
• During cystometrography (CMG), intravesical infusion of 0.25% AA significantly decreased the mean (se) bladder capacity to 28.8 (5.9)% of the capacity measured during saline infusion. • The TAMS stimulation inhibited AA-induced bladder overactivity at 5, 7 and 10 Hz, and significantly increased the mean (se) bladder capacity to 61.8 (9.9)%, 51.3 (14.5)%, 53.6 (14.9)%, respectively, of the control capacity during saline infusion, whereas stimulation at 20-40 Hz had no effect. • Under isovolumetric conditions at a bladder volume ranging between 130 to 160% of the bladder capacity measured during AA infusion, TAMS stimulation at all frequencies (5-40 Hz) significantly suppressed the irritation-induced rhythmic bladder contractions, reduced the area under the bladder pressure curve, and decreased the frequency of bladder contractions. However, the amplitude of rhythmic bladder contractions was only significantly decreased at stimulation frequencies of 5-20 Hz. • At bladder volumes above the AA control capacity, TAMS stimulation with frequencies of 20-30 Hz had an excitatory effect, resulting in large amplitude (>25 cmH(2) O) bladder contractions.
• TAMS stimulation targeting the cat pudendal nerve can inhibit C-fibre afferent-mediated bladder overactivity. • Thus, clinical research seems warranted to explore the usefulness of this technology for patients with overactive bladder symptoms.
BJU International 08/2011; 109(5):782-7. · 2.84 Impact Factor
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ABSTRACT: We investigated the effects of tibial nerve stimulation on bladder overactivity induced by acetic acid irritation.
Cystometry was performed in 10 α-chloralose anesthetized female cats by infusing saline or acetic acid through a urethral catheter that was secured by a ligature around the urethra. Intravesical infusion of 0.25% acetic acid was used to irritate the bladder and induce bladder overactivity. Multiple cystometrograms were done before, during and after tibial nerve stimulation to determine the inhibitory effect on the micturition reflex.
Infusion of 0.25% acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to about 20% of control capacity measured during saline infusion. Tibial nerve stimulation at low (5 Hz) or high (30 Hz) frequency significantly increased bladder capacity to about 40% of saline control capacity when it was applied during acetic acid infusion cystometrogram. Bladder contraction amplitude was smaller during acetic acid irritation than during saline distention due to significantly smaller bladder capacity. Tibial nerve stimulation at 5 Hz increased bladder capacity and bladder contraction amplitude.
Activation of somatic afferents in the tibial nerve of cats can partially reverse the bladder overactivity induced by intravesical administration of a chemical irritant that activates C-fiber afferent nerves. These data are consistent with clinical studies showing that tibial nerve neuromodulation is effective treatment for overactive bladder symptoms.
The Journal of urology 07/2011; 186(1):326-30. · 4.02 Impact Factor
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ABSTRACT: The mechanism of axonal conduction block induced by ultra-high frequency (≥ 20 kHz) biphasic electrical current was investigated using a lumped circuit model of the amphibian myelinated axon based on Frankenhaeuser-Huxley (FH) equations. The ultra-high frequency stimulation produces constant activation of both sodium and potassium channels at the axonal node under the block electrode causing the axonal conduction block. This blocking mechanism is different from the mechanism when the stimulation frequency is between 4 kHz and 10 kHz, where only the potassium channel is constantly activated. The minimal stimulation intensity required to induce a conduction block increases as the stimulation frequency increases. The results from this simulation study are useful to guide future animal experiments to reveal the different mechanisms underlying nerve conduction block induced by high-frequency biphasic electrical current.
Journal of Computational Neuroscience 04/2011; 31(3):615-23. · 2.51 Impact Factor
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ABSTRACT: Bladder reflexes evoked by stimulation of pudendal afferent nerves (PudA-to-Bladder reflex) were studied in normal and chronic spinal cord injured (SCI) adult cats to examine the reflex plasticity. Physiological activation of pudendal afferent nerves by tactile stimulation of the perigenital skin elicits an inhibitory PudA-to-Bladder reflex in normal cats, but activates an excitatory reflex in chronic SCI cats. However, in both normal and chronic SCI cats electrical stimulation applied to the perigenital skin or directly to the pudendal nerve induces either inhibitory or excitatory PudA-to-Bladder reflexes depending on stimulation frequency. An inhibitory response occurs at 3-10 Hz stimulation, but becomes excitatory at 20-30 Hz. The inhibitory reflex activated by electrical stimulation significantly (P<0.05) increases the bladder capacity to about 180% of control capacity in normal and chronic SCI cats. The excitatory reflex significantly (P<0.05) reduces bladder capacity to about 40% of control capacity in chronic SCI cats, but does not change bladder capacity in normal cats. Electrical stimulation of pudendal afferent nerves during slow bladder filling elicits a large amplitude bladder contraction comparable to the contraction induced by distension alone. A bladder volume about 60% of bladder capacity was required to elicit this excitatory reflex in normal cats; however, in chronic SCI cats a volume less than 20% of bladder capacity was sufficient to unmask an excitatory response. This study revealed the co-existence of both inhibitory and excitatory PudA-to-Bladder reflex pathways in cats before and after chronic SCI. However our data combined with published electrophysiological data strongly indicates that the spinal circuitry for both the excitatory and inhibitory PudA-to-Bladder reflexes undergoes a marked reorganization after SCI.
Experimental Neurology 03/2011; 228(1):109-17. · 4.70 Impact Factor
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ABSTRACT: To develop a non-invasive neuromodulation method to regulate bladder activity.
Neuromodulation of bladder activity was investigated in felines with an intact spinal cord under α-chloralose anesthesia using a transcutaneous stimulation method with surface electrodes attached to the skin area between the base of the tail and the sciatic notch.
The bladder could be either inhibited or excited depending on stimulation frequency and bladder volume. With the bladder distended to induce large amplitude rhythmic isovolumetric bladder contractions, stimulation at a frequency between 5 and 7 Hz significantly suppressed the contractions. Stimulation applied during a cystometrogram (CMG) also increased bladder capacity by 44.3 ± 10.8%. At a frequency between 20 and 40 Hz the inhibitory effect on rhythmic bladder contractions was weak and did not increase bladder capacity during CMG. At low bladder volumes ranging between 60% and 100% of the bladder capacity 20 Hz stimulation-induced small amplitude (21.2 ± 14.6 cmH(2) O) bladder contractions. However, stimulation at 20 Hz induced large amplitude (111.7 ± 22.2 cmH(2) O) bladder contractions at a bladder volume about 100-110% of the bladder capacity after the rhythmic bladder contractions were completely inhibited by the inhibitory 5 Hz stimulation. Conclusions: Both inhibitory and excitatory effects on bladder activity can be obtained in cats using the non-invasive neural stimulation approach. This pre-clinical study warrants a further clinical trial to investigate the possibility of using this non-invasive stimulation method to treat incontinence or urinary retention.
Neurourology and Urodynamics 03/2011; 30(8):1686-94. · 2.96 Impact Factor
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ABSTRACT: Inhibition of bladder activity by tibial nerve stimulation was investigated in α-chloralose-anesthetized cats with an intact spinal cord. Short-duration (3-5 min) tibial nerve stimulation at both low (5 Hz) and high (30 Hz) frequencies applied repeatedly during rhythmic isovolumetric bladder contractions was effective in inhibiting reflex bladder activity. Both frequencies of stimulation were also effective in inducing inhibition that persisted after the termination of the stimulation. The poststimulation inhibitory effect induced by the short-duration stimulation significantly increased bladder capacity to 181.6 ± 24.36% of the control capacity measured before applying the stimulation. Thirty-minute continuous stimulation induced prolonged poststimulation inhibition of bladder activity, which lasted for more than 2 h and significantly increased bladder capacity to 161.1 ± 2.9% of the control capacity. During the poststimulation periods, 5-Hz stimulation applied during the cystometrogram elicited a further increase (~30% on average) in bladder capacity, but 30-Hz stimulation was ineffective. These results in cats support the clinical observation that tibial nerve neuromodulation induces a long-lasting poststimulation inhibitory effect that is useful in treating overactive bladder symptoms.
AJP Renal Physiology 02/2011; 300(2):F385-92. · 4.42 Impact Factor
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ABSTRACT: To investigate the possibility of suppressing bladder overactivity by electrical activation of somatic afferent nerves in the foot.
Cats with an intact spinal cord were studied under α-chloralose anaesthesia. Bladder pressure was recorded via a urethral catheter. Foot stimulation was applied via surface pad electrodes attached to the skin of the front or hind foot.
Reflex micturition was inhibited by electrical stimulation of the hind foot at either low (5 Hz) or high (20 Hz) frequencies, but stimulation of the front foot was ineffective. The mean (sem) bladder capacity during a saline infusion cystometrogram (CMG) was significantly (P < 0.05) increased to 153.2 (18.2)% and 136.9 (14.3)% of the control bladder capacity by stimulation at frequencies of 5 Hz and 20 Hz, respectively. Intravesical infusion of 0.25% acetic acid (AA) induced bladder overactivity and reduced bladder capacity to 20.3 (8.9)% of the control capacity measured during saline infusion. Foot stimulation inhibited the AA-induced bladder overactivity recorded under isovolumetric conditions, and significantly (P < 0.05) increased bladder capacity during AA infusion. However, it only restored the small bladder capacity caused by AA irritation to 40-50% of the control bladder capacity measured during saline infusion. The effect of foot stimulation did not persist after termination of stimulation during repeated CMG tests.
This study shows the potential of noninvasive transcutaneous electrical stimulation of somatic nerves in the foot to inhibit reflex bladder activity and treat overactive bladder symptoms.
BJU International 01/2011; 107(2):303-9. · 2.84 Impact Factor
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ABSTRACT: To determine the involvement of opioid receptors in the inhibitory pudendal-to-bladder reflex, the effect of naloxone (0.01-1 mg/kg, i.v.), an opioid receptor antagonist, on the inhibition of bladder activity evoked by pudendal nerve stimulation was investigated in alpha-chloralose anesthetized cats. The inhibition of reflex isovolumetric bladder contractions induced by pudendal nerve stimulation (5-10 Hz) at intensity threshold (T) for producing complete inhibition was significantly suppressed by naloxone at a high dose (0.3 mg/kg). However, the inhibition elicited at higher intensities (1.5-3 T) was not changed. Naloxone (1 mg/kg) did not alter the frequency dependence of the inhibitory effect of pudendal stimulation. During cystometrograms (CMGs) pudendal nerve stimulation significantly increased bladder capacity to 155.1+/-24.5% and 163.4+/-10% of the control at stimulation intensities of 1 T and 1.5-3 T, respectively. After administration of naloxone (1 mg/kg), the bladder capacity during pudendal nerve stimulation at inhibition threshold (1 T) was not significantly different from control, but it was significantly increased at higher intensities (1.5-3 T). Naloxone alone markedly reduced bladder capacity to 43+/-11.1% of the control, and pudendal stimulation completely reversed this facilitatory effect. This study revealed that activation of opioid receptors contributes to or facilitates the inhibitory pudendal-to-bladder reflex. The reduction in bladder capacity after naloxone treatment also indicates that endogenous opioid peptides mediate a tonic inhibition of micturition. Understanding the neurotransmitter mechanisms involved in the inhibitory pudendal-to-bladder reflex could promote the development of new treatments for bladder overactivity and incontinence.
Experimental Neurology 04/2010; 224(1):282-91. · 4.70 Impact Factor
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ABSTRACT: The modulation of axonal excitability by high-frequency biphasic (HFB) electrical current was analyzed using a lumped-circuit model of the myelinated axon based on Schwarz-Reid-Bostock (SRB) equations. The results show that axonal excitability could be either increased or decreased by HFB current depending on the current intensity. The increase of axonal excitability is due to the high level of sodium channel activation, whereas the activation of both fast and slow potassium channels plays an important role in decreasing axonal excitability. As the HFB current intensity increases, the location determining the axonal excitability changes from the nodes under the electrode within the "main lobe" region of the activating function to the nodes away from the electrode in the "side lobe" region of the activating function. This simulation study also shows that the modulation of axonal excitability by HFB electrical current could be potentially useful to selectively activate the small nerve fibers in a compound nerve trunk without activating the large fibers. Understanding how HFB electrical current modulates the axonal excitability will further elucidate the possible mechanisms underlying the nerve conduction block induced by HFB electrical current.
IEEE Transactions on Biomedical Engineering 10/2009; · 2.28 Impact Factor
