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

Tai, Changfeng; Larson, Jeffrey; Ogagan, P. Dafe; Chen, Guoqing; Shen, Bing; Wang, Jicheng; Roppolo, James R.; Groat, William C. de

doi:10.1152/ajprenal.00609.2011

Cited by 54 publications

(102 citation statements)

References 26 publications

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“…Although previous reports suggested that separate pathways may govern inhibition of nociceptive and nonnociceptive bladder contractions (44,56), GABAergic mechanisms appear critical for inhibition of both types of contractions. A recent study of low-dose picrotoxin found that picrotoxin blocked inhibition of nociceptive, but not nonnociceptive, bladder contractions (56).…”

Section: Gabaergic Mechanisms Participate In Inhibition Of Both Nocicmentioning

confidence: 81%

“…A 3.5-to 5-Fr catheter was used to occlude the urethra during bladder filling and isovolumetric conditions. The threshold volume for distension-evoked reflex contractions (DECs) was found by filling the bladder at 1-2 ml/min with either room temperature saline or 0.25% acetic acid (AA), used to irritate the bladder and mimic OAB symptoms (44). Electromyographic (EMG) activity was detected from the external anal sphincter (EAS) with paired wire electrodes, amplified (1,000), filtered (10 Hz-10 kHz), and recorded.…”

Section: Methodsmentioning

confidence: 99%

“…Naloxone blocked bladder inhibition by low-amplitude pudendal afferent stimulation in cats (7) and mechanical skin stimulation in rats (23). Inhibition of bladder contractions evoked by the infusion of AA, but not saline, with tibial nerve stimulation was blocked by naloxone (44). Later experiments demonstrated that naloxone had no effect on pudendal stimulation-evoked inhibition of bladder overactivity in cats (28).…”

Section: Other Mechanisms May Not Be Necessary For Bladder Inhibitionmentioning

confidence: 99%

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A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation

McGee

Danziger

Bamford

et al. 2014

American Journal of Physiology-Renal Physiology

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McGee MJ, Danziger ZC, Bamford JA, Grill WM. A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation. Am J Physiol Renal Physiol 307: F921-F930, 2014. First published August 20, 2014 doi:10.1152/ajprenal.00330.2014.-Electrical stimulation of pudendal afferents can inhibit bladder contractions and increase bladder capacity. Recent results suggest that stimulation-evoked bladder inhibition is mediated by a mechanism other than activation of sympathetic bladder efferents in the hypogastric nerve, generating ␣-adrenergic receptor-mediated inhibition at the vesical ganglia and/or ␤-adrenergic receptor-mediated direct inhibition of the detrusor muscle. We investigated several inhibitory neurotransmitters that may instead be necessary for stimulation-evoked inhibition and found that intravenous picrotoxin, a noncompetitive GABAA antagonist, significantly and reversibly blocked pudendal afferent stimulation-evoked inhibition of bladder contractions in a dose-dependent manner. Similarly, intravenous picrotoxin also blocked pudendal afferent stimulation-evoked inhibition of nociceptive bladder contractions evoked by acetic acid infusion. Furthermore, intrathecal administration of picrotoxin at the lumbosacral spinal cord also blocked bladder inhibition by pudendal afferent stimulation. On the other hand, glycinergic, adrenergic, or opioidergic mechanisms were not necessary for bladder inhibition evoked by pudendal afferent stimulation. These results identify a lumbosacral spinal GABAergic mechanism of bladder inhibition evoked by pudendal afferent stimulation. electrical stimulation; bladder inhibition; pudendal nerve; dorsal nerve of the penis; GABA; picrotoxin IMPROVED BLADDER CONTROL IS an unmet need in persons with urinary incontinence (1) and in persons with neurological disease or injury, such as spinal cord injury (9). Electrical stimulation is a promising approach to treat overactive bladder (OAB), which can produce urgency and incontinence and impair quality of life (8, 32). In particular, pudendal afferent stimulation inhibits distension-evoked bladder contractions and improves continence (51). We sought to identify the mechanism(s) of bladder inhibition by pudendal afferent stimulation.Pudendal nerve (PN) stimulation may be an alternative to sacral nerve stimulation to improve continence (33), and in patients who do not respond to sacral neuromodulation it may be a successful treatment option (29,34,41). Low-frequency (ϳ10 Hz) pudendal afferent stimulation inhibits bladder contractions, thereby promoting continence in preclinical animal studies (4, 46, 52). Inhibition of bladder contractions and increased bladder capacities elicited by low-frequency pudendal afferent stimulation can also be achieved after chronic spinal cord injury (43, 47). However, the mechanisms of action of PN stimulation-mediated bladder inhibition are unclear, and such knowledge may improve patient selection and enable improvements in therapy.Initial studies suggested that pudendal afferent stimu...

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Section: Gabaergic Mechanisms Participate In Inhibition Of Both Nocicmentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Other Mechanisms May Not Be Necessary For Bladder Inhibitionmentioning

confidence: 99%

See 1 more Smart Citation

A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation

McGee

Danziger

Bamford

et al. 2014

American Journal of Physiology-Renal Physiology

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“…TNS parameters were chosen based on our previous studies in cats (24,27). The bladder was emptied after each CMG, and a 5-to 10-min rest period was inserted between CMGs to allow the distended detrusor to recover.…”

Section: Experimental Protocolmentioning

confidence: 99%

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

Ferroni

Slater

Shen

et al. 2015

American Journal of Physiology-Renal Physiology

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This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in ␣-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 (Ͼ2 h) poststimulation inhibition that significantly (P Ͻ 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 Ͻ 0.01) increased bladder capacity to 127.3 Ϯ 6.1% of saline control or 187.6 Ϯ 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 g) eliminated acute TNS inhibition and significantly (P Ͻ 0.05) reduced bladder capacity to 62.8 Ϯ 22.6% (intravenously) or 47.6 Ϯ 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. neuromodulation; brain stem; opioid; tibial; cat TIBIAL NEUROMODULATION, a Food and Drug Administration (FDA)-approved therapy for overactive bladder (OAB) symptoms, including urgency, frequency, and incontinence (7,19,20,29), is often used to treat patients whose symptoms are not completely controlled by drugs or who have unacceptable drug side effects (1,2,8,18). However, the mechanisms underlying tibial neuromodulation therapy are uncertain. Understanding the site of action and neurotransmitters involved in the inhibition of bladder reflexes by tibial nerve stimulation (TNS) is important for developing new OAB treatments by combining drug therapies with tibial neuromodulation to achieve a higher efficacy with fewer side effects (14,33).Previous studies in cats have demonstrated the inhibitory effect of TNS on bladder reflexes elicited during non-nociceptive saline distention as well as nociceptive acetic acid (AA) irritation (23,27). The failure of TNS to inhibit reflex bladder contractions during AA irritation in animals with acute spinal cord transection at the T9/T10 level (32) indicates that supraspinal neural circuits are necessary for TNS inhibition. However, it is unknown whether these supraspinal circuits are located in the forebrain or in the brain stem.A major clinical benefit of TNS is the long-lasting poststimulation inhibitory effect, which allows...

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“…Opioid receptors also seem to be involved in pudendal or tibial nerve neuromodualtion, which has been shown to be effective for the treatment of OAB symptoms, because naloxone, an opioid receptor antagonist, reverses the increasing effect of pudendal or tibial nerve stimulation on bladder capacity during intravesical saline infusion or bladder overactivity induced by intravesical acetic acid infusion, respectively, in cats (101,399,613). However, the site of action for opioid receptor activation during neuromodulation may not be limited to the spinal cord as naloxone was administered systemically in these studies.…”

Section: Neurotransmitters In Central Pathways Controlling Micturitionmentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

2009

Encyclopedia of Neuroscience

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This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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

Cited by 54 publications

References 26 publications

A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation

A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation

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

Neural Control of the Lower Urinary Tract

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