scholarly journals Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats

2015 ◽  
Vol 308 (1) ◽  
pp. R42-R49 ◽  
Author(s):  
Marc J. Rogers ◽  
Zhiying Xiao ◽  
Bing Shen ◽  
Jicheng Wang ◽  
Zeyad Schwen ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Nerve Stimulation ◽  
Adrenergic Receptor ◽  
Bladder Capacity ◽  
Spinal Reflex ◽  
Saline Control ◽  
Tibial Nerve Stimulation ◽  
Bladder Activity ◽  
Propranolol Treatment

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 iv, 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 contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, 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 iv, 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.

scholarly journals Role of spinal GABAA receptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

2014 ◽  
Vol 306 (7) ◽  
pp. F781-F789 ◽  
Author(s):  
Zhiying Xiao ◽  
Jeremy Reese ◽  
Zeyad Schwen ◽  
Bing Shen ◽  
Jicheng Wang ◽  
...  
Keyword(s):  
Gabaa Receptors ◽  
Bladder Capacity ◽  
Aminobutyric Acid ◽  
Saline Control ◽  
Receptor Subtype ◽  
High Dose ◽  
Multiple Threshold ◽  
Bladder Activity ◽  
Subtype A

Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive 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 nonnociceptive 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 it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) 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 it or 0.03–0.3 mg/kg iv) 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 nonnociceptive reflex bladder activities and in PNS inhibition of these activities.

scholarly journals Sympathetic afferents in the hypogastric nerve facilitate nociceptive bladder activity in cats

2019 ◽  
Vol 316 (4) ◽  
pp. F703-F711 ◽  
Author(s):  
Yan Zhang ◽  
Shun Li ◽  
Todd Yecies ◽  
Tara Morgan ◽  
Haotian Cai ◽  
...  
Keyword(s):  
Bladder Capacity ◽  
Saline Control ◽  
Pelvic Nerve ◽  
Analgesic Agent ◽  
Hypogastric Nerve ◽  
C Fibers ◽  
Pelvic Nerves ◽  
C Fiber ◽  
Bladder Activity

This study in α-chloralose-anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly ( P < 0.05) reduced bladder capacity to 45.0 ± 5.7% of the control capacity measured during a saline cystometrogram (CMG). In cats with the hypogastric nerves transected bilaterally, AA irritation also significantly ( P < 0.05) reduced bladder capacity, but the change was significantly smaller (capacity reduced to 71.5 ± 10.6% of saline control, P < 0.05) than that in cats with an intact hypogastric nerve. However, application of hypogastric nerve stimulation (HGNS: 20 Hz, 0.2 ms pulse width) to the central end of the transected nerves at an intensity (16 V) strong enough to activate C-fiber afferent axons facilitated the effect of AA irritation and further ( P < 0.05) reduced bladder capacity to 48.4 ± 7.4% of the saline control. This facilitation by HGNS was effective only at selected frequencies (1, 20, and 30 Hz) when the stimulation intensity was above the threshold for activating C-fibers. Tramadol (an analgesic agent) at 3 mg/kg iv completely blocked the nociceptive bladder activity and eliminated the facilitation by HGNS. HGNS did not alter non-nociceptive bladder activity induced by saline distention of the bladder. These results indicate that sympathetic afferents in the hypogastric nerve play an important role in the facilitation of the nociceptive bladder activity induced by bladder irritation that activates the silent C-fibers in the pelvic nerve.

scholarly journals Involvement of 5-HT3 receptors in pudendal inhibition of bladder overactivity in cats

2013 ◽  
Vol 305 (5) ◽  
pp. F663-F671 ◽  
Author(s):  
Zeyad Schwen ◽  
Yosuke Matsuta ◽  
Bing Shen ◽  
Jicheng Wang ◽  
James R. Roppolo ◽  
...  
Keyword(s):  
High Intensity ◽  
Bladder Capacity ◽  
Saline Control ◽  
Low Intensity ◽  
Afferent Nerves ◽  
Normal Bladder ◽  
Pudendal Neuromodulation ◽  
Bladder Symptoms ◽  
Bladder Activity

In the present study, the role of 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 the induction of anal twitching. AA irritation significantly reduced bladder capacity to 16.5 ± 3.3% of saline control capacity, whereas pudendal nerve stimulation (PNS) at 1.5–2 and 3–4 T restored the capacity to 82.0 ± 12% ( P = 0.0001) and 98.6 ± 15% ( P < 0.0001), respectively. Cumulative doses (1–3 mg/kg iv) of ondansetron, a 5-HT3 receptor antagonist, eliminated low-intensity (1.5–2 T) PNS inhibition and reduced high-intensity (3–4 T) PNS inhibition of bladder overactivity. During saline distention, PNS at 1.5–2 and 3–4 T 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 (0.003–3 mg/kg iv) 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 effects of low- and high-intensity PNS were not significantly different. After ondansetron (3 mg/kg) treatment, naloxone (1 mg/kg iv) 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 the treatment of overactive bladder symptoms.

scholarly journals Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats

2017 ◽  
Vol 312 (3) ◽  
pp. F482-F488 ◽  
Author(s):  
Xuewen Jiang ◽  
Michelle Yu ◽  
Jamie Uy ◽  
Thomas W. Fuller ◽  
Cameron Jones ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Cannabinoid Receptor ◽  
Bladder Capacity ◽  
Intrathecal Administration ◽  
Saline Control ◽  
Cb1 Receptors ◽  
Pudendal Neuromodulation ◽  
Bladder Disorders

The role of cannabinoid type 1 (CB1) receptors in tibial and pudendal neuromodulation of bladder overactivity induced by intravesical infusion of 0.5% acetic acid (AA) was determined in α-chloralose anesthetized cats. AA irritation significantly ( P < 0.01) reduced bladder capacity to 36.6 ± 4.8% of saline control capacity. Tibial nerve stimulation (TNS) at two or four times threshold (2T or 4T) intensity for inducing toe movement inhibited bladder overactivity and significantly ( P < 0.01) increased bladder capacity to 69.2 ± 9.7 and 79.5 ± 7.2% of saline control, respectively. AM 251 (a CB1 receptor antagonist) administered intravenously at 0.03 or 0.1 mg/kg significantly ( P < 0.05) reduced the inhibition induced by 2T or 4T TNS, respectively, without changing the prestimulation bladder capacity. However, intrathecal administration of AM 251 (0.03 mg) to L7 spinal segment had no effect on TNS inhibition. Pudendal nerve stimulation (PNS) also inhibited bladder overactivity induced by AA irritation, but AM 251 at 0.01–1 mg/kg iv had no effect on PNS inhibition or the prestimulation bladder capacity. These results indicate that CB1 receptors play an important role in tibial but not pudendal neuromodulation of bladder overactivity and the site of action is not within the lumbar L7 spinal cord. Identification of neurotransmitters involved in TNS or PNS inhibition of bladder overactivity is important for understanding the mechanisms of action underlying clinical application of neuromodulation therapies for bladder disorders.

scholarly journals Contribution of opioid and metabotropic glutamate receptor mechanisms to inhibition of bladder overactivity by tibial nerve stimulation

2013 ◽  
Vol 305 (2) ◽  
pp. R126-R133 ◽  
Author(s):  
Yosuke Matsuta ◽  
Abhijith D. Mally ◽  
Fan Zhang ◽  
Bing Shen ◽  
Jicheng Wang ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Nerve Stimulation ◽  
High Intensity ◽  
Metabotropic Glutamate Receptor ◽  
Tibial Nerve ◽  
Bladder Capacity ◽  
Saline Control ◽  
Metabotropic Glutamate ◽  
Tibial Nerve Stimulation ◽  
Group Ii

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 iv) 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 iv) 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 the development of new treatments for bladder disorders.

scholarly journals Prolonged poststimulation inhibition of bladder activity induced by tibial nerve stimulation in cats

2011 ◽  
Vol 300 (2) ◽  
pp. F385-F392 ◽  
Author(s):  
Changfeng Tai ◽  
Bing Shen ◽  
Mang Chen ◽  
Jicheng Wang ◽  
James R. Roppolo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Short Duration ◽  
Nerve Stimulation ◽  
Clinical Observation ◽  
Tibial Nerve ◽  
Bladder Capacity ◽  
Inhibitory Effect ◽  
Tibial Nerve Stimulation ◽  
Bladder Symptoms ◽  
Bladder Activity

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.

scholarly journals Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats

2015 ◽  
Vol 308 (8) ◽  
pp. F832-F838 ◽  
Author(s):  
Jeremy N. Reese ◽  
Marc J. Rogers ◽  
Zhiying Xiao ◽  
Bing Shen ◽  
Jicheng Wang ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Bladder Capacity ◽  
Spinal Reflex ◽  
Saline Control ◽  
Metabotropic Glutamate Receptor 5 ◽  
Contraction Amplitude ◽  
Metabotropic Glutamate ◽  
Bladder Contraction ◽  
C Fiber

This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (<50 cmH2O) and short duration (<20 s) at a smaller bladder capacity ∼80% of saline control capacity. PNS significantly ( P < 0.01) increased bladder capacity from 85.5 ± 10.1 to 137.3 ± 14.1 or 148.2 ± 11.2% at 2T or 4T stimulation, respectively, where T is the threshold intensity for PNS to induce anal twitch. MTEP {3-[(2-methyl-4-thiazolyl)ethynyl]pyridine; 3 mg/kg iv, a selective mGluR5 antagonist} completely removed the PNS inhibition and significantly ( P < 0.05) increased bladder capacity from 71.8 ± 9.9 to 94.0 ± 13.9% of saline control, but it did not change the bladder contraction amplitude. After propranolol (3 mg/kg iv, a β1/β2-adrenergic receptor antagonist) treatment, PNS inhibition remained but MTEP significantly ( P < 0.05) reduced the bladder contraction amplitude from 18.6 ± 2.1 to 6.6 ± 1.2 cmH2O and eliminated PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly ( P < 0.05) reduced the bladder contraction amplitude from 20.9 ± 3.2 to 8.1 ± 1.5 cmH2O on average demonstrating that spinal reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex.

scholarly journals Role of the brain stem in tibial inhibition of the micturition reflex in cats

2015 ◽  
Vol 309 (3) ◽  
pp. F242-F250 ◽  
Author(s):  
Matthew C. Ferroni ◽  
Rick C. Slater ◽  
Bing Shen ◽  
Zhiying Xiao ◽  
Jicheng Wang ◽  
...  
Keyword(s):  
Overactive Bladder ◽  
Brain Stem ◽  
Critical Role ◽  
Bladder Capacity ◽  
Saline Control ◽  
Tibial Nerve Stimulation ◽  
Normal Bladder ◽  
Decerebrate Cats ◽  
The Brain

This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly ( P < 0.05) increased bladder capacity to 30–60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly ( P < 0.01) increased bladder capacity to 127.3 ± 6.1% of saline control or 187.6 ± 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300–900 μg) eliminated acute TNS inhibition and significantly ( P < 0.05) reduced bladder capacity to 62.8 ± 22.6% (intravenously) or 47.6 ± 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes.

scholarly journals Sympathetic β-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity

2016 ◽  
Vol 311 (1) ◽  
pp. F78-F84 ◽  
Author(s):  
Brian T. Kadow ◽  
Timothy D. Lyon ◽  
Zhaocun Zhang ◽  
Vladimir Lamm ◽  
Bing Shen ◽  
...  
Keyword(s):  
Bladder Capacity ◽  
Saline Control ◽  
Hypogastric Nerve ◽  
Metabotropic Glutamate ◽  
Nociceptive Reflex ◽  
Peripheral Mechanism ◽  
Adrenergic Mechanism ◽  
Multiple Threshold ◽  
Bladder Activity

This study investigated the role of the hypogastric nerve and β-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly ( P < 0.01) increased bladder capacity to 184.7 ± 12.6% and 214.5 ± 10.4% of the control capacity. Propranolol (3 mg/kg iv) had no effect on PNS inhibition, but 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP; 1–3 mg/kg iv) significantly ( P < 0.05) reduced the inhibition. During AA irritation, the control bladder capacity was significantly ( P < 0.05) reduced to ∼22% of the saline control capacity. PNS at 2T and 4T significantly ( P < 0.01) increased bladder capacity to 406.8 ± 47% and 415.8 ± 46% of the AA control capacity. Propranolol significantly ( P < 0.05) reduced the bladder capacity to 276.3% ± 53.2% (at 2T PNS) and 266.5 ± 72.4% (at 4T PNS) of the AA control capacity, whereas MTEP (a metabotropic glutamate 5 receptor antagonist) removed the residual PNS inhibition. Bilateral transection of the hypogastric nerves produced an effect similar to that produced by propranolol. This study indicates that hypogastric nerves and a β-adrenergic mechanism in the detrusor play an important role in PNS inhibition of nociceptive but not non-nociceptive reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition.

scholarly journals Management of overactive bladder review: the role of percutaneous tibial nerve stimulation

2017 ◽  
Vol 25 (4) ◽  
pp. 245-54
Author(s):  
Elita Wibisono ◽  
Harrina E. Rahardjo
Keyword(s):  
Overactive Bladder ◽  
Nerve Stimulation ◽  
Tibial Nerve ◽  
Botulinum Toxin Injection ◽  
Treatment Options ◽  
Bladder Function ◽  
World Population ◽  
Percutaneous Tibial Nerve Stimulation ◽  
Tibial Nerve Stimulation

Overactive bladder (OAB) is a common condition that is experienced by around 455 million people (11% of the world population) and associated with significant impact in patients’ quality of life. The first line treatments of OAB are conservative treatment and anti-muscarinic medication. For the refractory OAB patients, the treatment options available are surgical therapy, electrical stimulation, and botulinum toxin injection. Among them, percutaneous tibial nerve stimulation (PTNS) is a minimally invasive option that aims to stimulate sacral nerve plexus, a group of nerve that is responsible for regulation of bladder function. After its approval by food and drug administration (FDA) in 2007, PTNS revealed considerable promise in OAB management. In this review, several non-comparative and comparative studies comparing PTNS with sham procedure, anti-muscarinic therapy, and multimodal therapy combining PTNS and anti-muscarinic had supportive data to this consideration.

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