Changfeng Tai

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (77)212.86 Total impact

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    ABSTRACT: This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch respectively. During a cystrometrogram (CMG) PNS at 2T and 4T significantly (p<0.05) increased bladder capacity from 58.0±4.7% to 85.8±10.3% and 96.5±10.7% respectively of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg i.v., a β1/β2-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (p<0.05) reduced to 64.5±9.5% and 64.7±7.3% respectively of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant (p<0.05). Propranolol treatment also significantly (p=0.0019) increased the amplitude of bladder contraction, but did not change the control bladder capacity. Naloxone (1 mg/kg i.v., an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg i.v., a ganglionic blocker) significantly (p<0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of β1/β2-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity.
    American journal of physiology. Regulatory, integrative and comparative physiology. 11/2014;
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    ABSTRACT: The goal of this study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid (AA) was used to irritate bladder, activate nociceptive afferent C-fibers and trigger spinal reflex bladder contractions (amplitude 19.3±2.9 cmH2O). Hexamethonium (a ganglionic blocker, i.v.) significantly (p<0.01) reduced the amplitude of the reflex bladder contractions to 8.5±1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2±1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited the reflex bladder contractions, while tibial nerve stimulation (TNS) failed to inhibit the bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows for the first time that after acute spinal cord transection reflex bladder contractions can be triggered by activating the nociceptive bladder afferent C-fibers using AA irritation. Understanding the sites of action for PNS or TNS inhibition is important for clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions.
    American journal of physiology. Renal physiology 07/2014; · 3.61 Impact Factor
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    ABSTRACT: The effect of a non-symmetric waveform on nerve conduction block induced by high-frequency biphasic stimulation is investigated using a lumped circuit model of the unmyelinated axon based on Hodgkin-Huxley equations. The simulation results reveal that the block threshold monotonically increases with the stimulation frequency for the symmetric stimulation waveform. However, a non-monotonic relationship between block threshold and stimulation frequency is observed when the stimulation waveform is non-symmetric. Constant activation of potassium channels by the high-frequency stimulation results in the increase of block threshold with increasing frequency. The non-symmetric waveform with a positive pulse 0.4-0.8 μs longer than the negative pulse blocks axonal conduction by hyperpolarizing the membrane and causes a decrease in block threshold as the frequency increases above 12-16 kHz. On the other hand, the non-symmetric waveform with a negative pulse 0.4-0.8 μs longer than the positive pulse blocks axonal conduction by depolarizing the membrane and causes a decrease in block threshold as the frequency increases above 40-53 kHz. This simulation study is important for understanding the potential mechanisms underlying the nerve block observed in animal studies, and may also help to design new animal experiments to further improve the nerve block method for clinical applications.
    Journal of Computational Neuroscience 06/2014; · 2.44 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e2–e3. · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e6. · 3.75 Impact Factor
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    ABSTRACT: This study is aimed at determining the effect of duloxetine (a serotonin-norepinephrine reuptake inhibitor) on pudendal inhibition of bladder overactivity. Cystometrograms were performed on 15 cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, pudendal nerve stimulation (PNS) at 5 Hz was applied to the right pudendal nerve at 2 and 4 times the threshold (T) intensity for inducing anal twitch. Duloxetine (0.03-3 mg/kg) was administered intravenously to determine the effect on PNS inhibition. AA irritation significantly (p<0.01) reduced bladder capacity to 27.9±4.6% of saline control capacity. PNS alone at both 2T and 4T significantly (p<0.01) inhibited bladder overactivity and increased bladder capacity to 83.6±7.6% and 87.5±7.7% of saline control, respectively. Duloxetine at low doses (0.03-0.3 mg/kg) caused a significant reduction in PNS inhibition without changing bladder capacity. However, at high doses (1-3 mg/kg) duloxetine significantly increased bladder capacity but still failed to enhance PNS inhibition. WAY100635 (a 5-HT1A receptor antagonist, 0.5-1 mg/kg, i.v.) reversed the suppressive effect of duloxetine on PNS inhibition and significantly (p<0.05) increased the inhibitory effect of duloxetine on bladder overactivity but did not enhance the effect of PNS. These results indicate that activation of 5-HT1A auto-receptors on the serotonergic neurons in the raphe nucleus may suppress duloxetine and PNS inhibition, suggesting that the co-administration of a 5-HT1A antagonist drug might be useful in enhancing the efficacy of duloxetine alone and/or the additive effect of PNS-duloxetine combination for the treatment of overactive bladder symptoms.
    Journal of Pharmacology and Experimental Therapeutics 03/2014; · 3.89 Impact Factor
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    ABSTRACT: Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and non-nociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA, 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce non-nociceptive bladder activity. To modulate the bladder reflex pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly (p<0.01) reduced bladder capacity to 34.3±7.1% of the saline control capacity; while PNS at 2T and 4T significantly (p<0.01) increased AA bladder capacity to 84.0±7.8% and 93.2±15.0%, respectively, of the saline control. Picrotoxin (0.4 mg, i.t.) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (i.v.) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly (p<0.05) reduced 2T PNS inhibition at low doses (0.01-0.1 mg/kg). During saline cystometry, PNS significantly (p<0.01) increased bladder capacity to 147.0±7.6% at 2T and 172.7±8.9% at 4T of control capacity; and picrotoxin (0.4 mg, i.t. or 0.03-0.3 mg/kg, i.v.) also significantly (p<0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and non-nociceptive reflex bladder activities and in PNS inhibition of these activities.
    AJP Renal Physiology 02/2014; · 4.42 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the effect of tibial nerve stimulation (TNS) on the micturition reflex. Experiments were conducted in 24 rats under urethane anesthesia. A catheter was inserted into the bladder via the bladder dome for saline infusion. A cuff electrode was placed around right tibial nerve for stimulation. TNS (5 Hz, 0.2 msec pulse width) at 2-4 times the threshold (T) intensity for inducing a toe movement was applied either during slow (0.08 mL/min) infusion of the bladder or for 30 min with an empty bladder. TNS had no effect on the micturition reflex when it was applied during slow bladder infusion. However, the 30-min TNS applied with an empty bladder induced poststimulation inhibition and significantly (P < 0.05) increased the bladder capacity to about 140% of prestimulation level in a 50-min period following the termination of stimulation. The bladder compliance was also significantly (P < 0.05) increased after the 30-min TNS. These results suggest that different mechanisms might exist in acute- and post-TNS inhibition of micturition reflex. The animal model developed in this study will be very useful for further investigations of the neurotransmitter mechanisms underlying tibial neuromodulation of bladder function.
    Physiological reports. 01/2014; 2(1):e00205.
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    ABSTRACT: The study aims to determine the functionality of a wireless-controlled implantable stimulator designed for stimulation and block of the pudendal nerve. In five cats under α-chloralose anesthesia, the stimulator was implanted underneath the skin on the left side in the lower back along the sacral spine. Two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves in addition to one bipolar cuff electrode that was implanted on the left side central to the tripolar cuff electrode. The stimulator provided high-frequency (5-20 kHz) biphasic stimulation waveforms to the two tripolar electrodes and low-frequency (1-100 Hz) rectangular pulses to the bipolar electrode. Bladder and urethral pressures were measured to determine the effects of pudendal nerve stimulation (PNS) or block. The maximal (70-100 cmH2 O) urethral pressure generated by 20-Hz PNS applied via the bipolar electrode was completely eliminated by the pudendal nerve block induced by the high-frequency stimulation (6-15 kHz, 6-10 V) applied via the two tripolar electrodes. In a partially filled bladder, 20-30 Hz PNS (2-8 V, 0.2 ms) but not 5 Hz stimulation applied via the bipolar electrode elicited a large sustained bladder contraction (45.9 ± 13.4 to 52.0 ± 22 cmH2 O). During cystometry, the 5 Hz PNS significantly (p < 0.05) increased bladder capacity to 176.5 ± 27.1% of control capacity. The wireless-controlled implantable stimulator successfully generated the required waveforms for stimulation and block of pudendal nerve, which will be useful for restoring bladder functions after spinal cord injury.
    Neuromodulation 12/2013; · 1.19 Impact Factor
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    ABSTRACT: The purpose of this study is to determine whether duloxetine (a serotonin-norepinephrine reuptake inhibitor) combined with transcutaneous foot stimulation or WAY100635 (a 5HT1A antagonist) can enhance inhibition of bladder overactivity in cats. Cystometrograms were performed on 8 cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, foot stimulation (5 Hz) was applied via transcutaneous pad electrodes to the right hind foot at 2 and 4 times the threshold (T) intensity for inducing a toe twitch. Duloxetine (0.003-3 mg/kg) was administered intravenously to determine the effect of combination treatment. After the 3 mg/kg dose of duloxetine, WAY100635 (0.5 mg/kg) was given intravenously. AA irritation significantly (P<0.0001) reduced bladder capacity to 42.7±7.4% of saline control capacity. Foot stimulation alone at both 2T and 4T significantly (P<0.0001) inhibited bladder overactivity and increased bladder capacity to 66.7±6.3% and 85.7±6.5% of saline control, respectively. Duloxetine alone dose-dependently inhibited bladder overactivity and completely restored bladder capacity to saline control (109±15.5%) at 3 mg/kg. Although duloxetine combined with foot stimulation did not further enhance the inhibition, WAY100635 (0.5 mg/kg) given after 3 mg/kg duloxetine further increased (P=0.008) bladder capacity to 162.2±22.5% of saline control. Although duloxetine and foot stimulation independently inhibited bladder overactivity, combined treatment did not enhance the inhibition. Duloxetine combined with WAY100635, however, synergistically enhanced bladder inhibition, indicating a potential novel treatment for overactive bladder if duloxetine is combined with a 5HT1A receptor antagonist drug.
    AJP Renal Physiology 10/2013; · 4.42 Impact Factor
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    ABSTRACT: To determine if electrical stimulation of somatic afferent nerves in the foot can delay bladder filling sensations and increase bladder capacity in healthy humans without overactive bladder (OAB). Eight subjects underwent 90 minutes of foot stimulation using skin surface electrodes connected to a transcutaneous electrical nerve stimulator. The electrodes were attached to the bottom of the foot. Subjects completed a 3-day voiding diary during which foot stimulation was applied on the second day. Stimulation parameters included a pulse frequency of 5 Hz, a rectangular waveform pulse width of 0.2 ms, and an intensity of 2-6 times the minimal stimulation current necessary to induce a toe twitch. The stimulation intensity was set by each subject to a maximal level without causing any discomfort. The subjects were provided 500-1000 mL of water to drink during stimulation. The average volume per void was 350±22 mL during the 24 hour period prior to foot stimulation, and this voided volume increased to 547±52 mL (p<0.01) for up to 5 hours after the stimulation. The average voided volume returned to 363±21 mL within 36 hours after stimulation. There were no adverse events. Foot stimulation can delay bladder filling sensations and significantly increase bladder capacities in healthy humans without OAB. Although the study group was small, our results support moving forward with clinical trials of foot neuromodulation in OAB patients.
    The Journal of urology 10/2013; · 3.75 Impact Factor
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    ABSTRACT: To determine whether transcutaneous foot stimulation combined with a lower dose tolterodine would inhibit bladder overactivity more effectively than either treatment alone. Cystometrograms were performed on α-chloralose anesthetized cats (N = 6) by infusing 0.25% acetic acid (AA) to induce bladder overactivity. Foot stimulation (5 Hz) was applied at 2 and 4 times the threshold (T) intensity in volts (i.e., 2T or 4T) for inducing toe movement to inhibit bladder overactivity. Cumulative doses of tolterodine (0.003-0.3 mg/kg, i.v.) were also administered to determine the effect of combination treatment. AA irritation of the bladder significantly (P < 0.0001) reduced bladder capacity to 23.6 ± 7.1% of saline control capacity. Foot stimulation alone at 2T and 4T inhibited bladder overactivity and significantly (P < 0.0001) increased bladder capacity to 50.7 ± 6.8% and 79.0 ± 11.6% of saline control, respectively. Tolterodine alone at 0.3 mg/kg significantly (P < 0.05) increased bladder capacity to 65.6 ± 15.5% of saline control. However, when tolterodine at a threshold dose (0.3 mg/kg) was combined with foot stimulation, the bladder capacity was significantly (P < 0.05) increased to 86.2 ± 6.2% and 107.9 ± 10.6% by 2T and 4T stimulation, respectively. Complete inhibition of bladder overactivity could be achieved at a lower tolterodine dose (0.1 mg/kg) when combined with 4T stimulation (97.0 ± 11.2% of saline control). The amplitude of micturition contraction was not changed by tolterodine treatment. This study suggests a novel, efficacious, non-invasive therapy by combining foot stimulation with a lower dose tolterodine to treat bladder overactivity. It also provides the first objective evidence supporting an additive therapeutic benefit of neuromodulation and antimuscarinic combination treatment. Neurourol. Urodynam. © 2013 Wiley Periodicals, Inc.
    Neurourology and Urodynamics 08/2013; · 2.67 Impact Factor
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    ABSTRACT: The role of the 5-HT3 receptors in pudendal neuromodulation of bladder activity and its interaction with opioid receptors were investigated in anesthetized cats. The bladder was distended with either saline to induce normal bladder activity or with 0.25% acetic acid (AA) to induce bladder overactivity. Pudendal afferent nerves were activated by 5 Hz stimulation at multiples of the threshold (T) intensity for inducing anal twitching. AA irritation significantly reduced bladder capacity to 16.5±3.3% of saline control capacity, while pudendal nerve stimulation (PNS) at 1.5-2T and 3-4T restored the capacity to 82.0±12% (P=0.0001) and 98.6±15% (P<0.0001), respectively. Cumulative doses (1-3mg/kg, i.v.) of ondansetron, a 5-HT3 receptor antagonist, eliminated low intensity (1.5-2T) PNS inhibition and reduced high intensity (3-4T) PNS inhibition of bladder overactivity. During saline distention, PNS at 1.5-2T and 3-4T significantly increased bladder capacity to 173.2±26.4% (P=0.036) and 193.2±22.5% (P=0.008), respectively, of saline control capacity, but ondansetron (0.003-3mg/kg, i.v.) did not alter PNS inhibition. Ondansetron (0.1-3 mg/kg) also significantly (P<0.05) increased control bladder capacity (50-200%) during either AA irritation or saline distention. In both conditions the effect of low and high intensity PNS were not significantly different. After ondansetron (3 mg/kg) treatment, naloxone (1 mg/kg, i.v.) significantly (P<0.05) decreased control bladder capacity (40-70%) during either AA irritation or saline distention, but failed to affect PNS inhibition. This study revealed that activation of 5-HT3 receptors has a role in PNS inhibition of bladder overactivity. It also indicated that 5-HT3 receptor antagonists might be useful for treating overactive bladder symptoms.
    AJP Renal Physiology 07/2013; · 4.42 Impact Factor
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    ABSTRACT: The role of 5-HT2 and opioid receptors in pudendal inhibition of bladder activity induced by intravesical infusion of saline or 0.25% acetic acid (AA) was investigated in anesthetized cats using methysergide (a 5-HT2 receptor antagonist) and naloxone (an opioid receptor antagonist). AA irritated the bladder and significantly (P<0.0001) reduced bladder capacity to 27.0±7.4% of saline control capacity. Pudendal nerve stimulation (PNS) at multiples of the threshold (T) intensity for inducing anal sphincter twitching restored bladder capacity to 60.1± 8.0% at 1-2T (P<0.0001) and 92.2±14.1% at 3-4T (P=0.001) of the saline control capacity. Methysergide (0.03-1 mg/kg, i.v.) suppressed low intensity (1-2T) PNS inhibition but not high intensity (3-4T) inhibition, and also significantly (P<0.05) increased control bladder capacity at the dosage of 0.3-1 mg/kg. During saline infusion without AA irritation, PNS significantly increased bladder capacity to 150.8±9.9% at 1-2T (P<0.01) and 180.4±16.6% at 3-4T (P<0.01) of the saline control capacity. Methysergide (0.1-1 mg/kg) significantly (P<0.05) increased saline control bladder capacity and suppressed PNS inhibition at the dosage of 0.03-1 mg/kg. After methysergide treatment (1 mg/kg), naloxone significantly (P<0.05) reduced control bladder capacity during AA infusion but had no effect during saline infusion. Naloxone also had no influence on PNS inhibition. These results suggest that 5-HT2 receptors play a role in PNS inhibition of reflex bladder activity and interact with opioid receptors in micturition reflex pathway. Understanding neurotransmitter mechanisms underlying pudendal neuromodulation is important for the development of new treatments for bladder disorders.
    Experimental Neurology 05/2013; · 4.65 Impact Factor
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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; · 3.28 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; · 3.75 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; · 3.75 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. · 4.38 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. · 3.75 Impact Factor

Publication Stats

910 Citations
212.86 Total Impact Points

Institutions

  • 1995–2014
    • University of Pittsburgh
      • • Department of Urology
      • • School of Medicine
      • • Rehabilitation Science and Technology
      Pittsburgh, Pennsylvania, United States
  • 2013
    • Beijing Jiaotong University
      Peping, Beijing, China
    • China Rehabilitation Research Center
      北江, Zhejiang Sheng, China
  • 2006
    • Capital Medical University
      • School of Biomedical Engineering
      Peping, Beijing, China
  • 2005
    • The Ohio State University
      • Department of Veterinary Clinical Sciences
      Columbus, Ohio, United States