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

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.

Download Full-text

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

AJP Renal Physiology ◽

10.1152/ajprenal.00679.2013 ◽

2014 ◽

Vol 306 (7) ◽

pp. F781-F789 ◽

Cited By ~ 28

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.

Download Full-text

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

AJP Renal Physiology ◽

10.1152/ajprenal.00522.2018 ◽

2019 ◽

Vol 316 (4) ◽

pp. F703-F711 ◽

Cited By ~ 4

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.

Download Full-text

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

AJP Renal Physiology ◽

10.1152/ajprenal.00586.2016 ◽

2017 ◽

Vol 312 (3) ◽

pp. F482-F488 ◽

Cited By ~ 3

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.

Download Full-text

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00368.2014 ◽

2015 ◽

Vol 308 (1) ◽

pp. R42-R49 ◽

Cited By ~ 13

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.

Download Full-text

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

AJP Renal Physiology ◽

10.1152/ajprenal.00135.2015 ◽

2015 ◽

Vol 309 (3) ◽

pp. F242-F250 ◽

Cited By ~ 18

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.

Download Full-text

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

AJP Renal Physiology ◽

10.1152/ajprenal.00180.2016 ◽

2016 ◽

Vol 311 (1) ◽

pp. F78-F84 ◽

Cited By ~ 14

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.

Download Full-text

Subdiaphragmatic vagal afferent nerves modulate visceral pain

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00588.2007 ◽

2008 ◽

Vol 294 (6) ◽

pp. G1441-G1449 ◽

Cited By ~ 50

Author(s):

S. L. Chen ◽

X. Y. Wu ◽

Z. J. Cao ◽

J. Fan ◽

M. Wang ◽

...

Keyword(s):

Vagus Nerve ◽

High Intensity ◽

Visceral Pain ◽

Light Level ◽

Vagal Afferents ◽

Abdominal Muscles ◽

Low Intensity ◽

C Fibers ◽

Afferent Nerves ◽

Vagal Afferent

Activation of the vagal afferents by noxious gastrointestinal stimuli suggests that vagal afferents may play a complex role in visceral pain processes. The contribution of the vagus nerve to visceral pain remains unresolved. Previous studies reported that patients following chronic vagotomy have lower pain thresholds. The patient with irritable bowel syndrome has been shown alteration of vagal function. We hypothesize that vagal afferent nerves modulate visceral pain. Visceromotor responses (VMR) to graded colorectal distension (CRD) were recorded from the abdominal muscles in conscious rats. Chronic subdiaphragmatic vagus nerve sections induced 470, 106, 51, and 54% increases in VMR to CRD at 20, 40, 60 and 80 mmHg, respectively. Similarly, at light level of anesthesia, topical application of lidocaine to the subdiaphragmatic vagus nerve in rats increased VMR to CRD. Vagal afferent neuronal responses to low or high-intensity electrical vagal stimulation (EVS) of vagal afferent Aδ or C fibers were distinguished by calculating their conduction velocity. Low-intensity EVS of Aδ fibers (40 μA, 20 Hz, 0.5 ms for 30 s) reduced VMR to CRD at 40, 60, and 80 mmHg by 41, 52, and 58%, respectively. In contrast, high-intensity EVS of C fibers (400 μA, 1 Hz, 0.5 ms for 30 s) had no effect on VMR to CRD. In conclusion, we demonstrated that vagal afferent nerves modulate visceral pain. Low-intensity EVS that activates vagal afferent Aδ fibers reduced visceral pain. Thus EVS may potentially have a role in the treatment of chronic visceral pain.

Download Full-text

Differential role of opioid receptors in tibial nerve inhibition of nociceptive and nonnociceptive bladder reflexes in cats

AJP Renal Physiology ◽

10.1152/ajprenal.00609.2011 ◽

2012 ◽

Vol 302 (9) ◽

pp. F1090-F1097 ◽

Cited By ~ 46

Author(s):

Changfeng Tai ◽

Jeffrey A. Larson ◽

P. Dafe Ogagan ◽

Guoqing Chen ◽

Bing Shen ◽

...

Keyword(s):

Opioid Receptors ◽

Tibial Nerve ◽

Bladder Capacity ◽

Saline Infusion ◽

Saline Control ◽

Afferent Inhibition ◽

Urinary Tract Disorders ◽

Acute Increase ◽

Nerve Inhibition

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 cmH2O) 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.

Download Full-text

The Mediational Mole of Social Influence in the Perception of Exertion

Journal of Sport Psychology ◽

10.1123/jsp.8.2.88 ◽

1986 ◽

Vol 8 (2) ◽

pp. 88-104 ◽

Cited By ~ 17

Author(s):

Charles J. Hardy ◽

Evelyn G. Hall ◽

Perry H. Prestholdt

Keyword(s):

Social Influence ◽

High Intensity ◽

Physiological Responses ◽

Cycle Ergometer ◽

The Self ◽

Self Perception ◽

Psychological Variables ◽

Low Intensity ◽

Mediational Role

Two experiments are reported that investigate the mediational role of social influence in the self-perception of exertion. In Experiment 1, subjects performed three 15-min trials on a cycle ergometer at 25%, 50%, and 75% VO2max, both in the presence of another performer (a coactor) and alone. The results indicated that subjects reported lower RPEs when performing with another, particularly at the moderate (50%) intensity. In Experiment 2, subjects performed one 15-min trial at 50% of VO2max, both alone and in the presence of another performer (coactor) exhibiting nonverbal "cues" that the work was either extremely easy or extremely difficult. The results indicated that subjects exposed to the low-intensity cue information reported lower RPEs than when performing alone. Mo significant differences were noted for those subjects exposed to the high-intensity cue information. These findings are discussed in terms of a self-presentational analysis. That such effects were evidenced without physiological responses (VO2, VE, HR) accompanying them supports the notion that psychological variables can play a significant role in the self-perception of exertion. These results, however, are limited to untrained individuals exercising at moderate intensities.

Download Full-text

The Role of Callistemon Fruits and Infructescences in Protecting Seeds from Heat in Fires

Australian Journal of Botany ◽

10.1071/bt97026 ◽

1998 ◽

Vol 46 (2) ◽

pp. 235 ◽

Cited By ~ 8

Author(s):

Claire L. Brown ◽

Robert J. Whelan

Keyword(s):

High Temperature ◽

Seed Germination ◽

High Intensity ◽

Room Temperature ◽

Seed Viability ◽

Protective Role ◽

Percentage Germination ◽

Low Intensity ◽

Australian Plant

A number of Australian plant species tolerate fires because seeds are protected in woody fruits and are released after fire, but there is little information about the role of the fruit, or a collection of fruits, in protecting seed from the heat of a fire. This study examined the effects of various temperatures applied to infructescences of Callistemon citrinus (Curtis) Skeels on seed germination. The protective role of the dense collection of fruits in maintaining seed viability was tested by experimentally ‘thinning’ infructescences before heating. Heating of infructescences significantly increased the percentage of seeds germinating from less than 20% at room temperature to over 35% at 200˚C, but caused a decline, with further temperature increase to 800˚C. There was a slight but statistically significant increase in the percentage germination of seeds from thinned infructescences. Increased germination following exposure to high temperature may be a way for a plant to synchronise germination after high-intensity fire, while spreading it out if seeds are released in the absence of fire or after a low-intensity fire.

Download Full-text