Role of the endogenous opioid system in modulation of urinary bladder activity by spinal nerve stimulation

Su, Xin; Nickles, Angela; Nelson, Dwight E.

doi:10.1152/ajprenal.00090.2013

Cited by 21 publications

(19 citation statements)

References 26 publications

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“…Recently, an important role of naloxone-sensitive m ORs was also identified in sacral neuromodulation of isovolumetric bladder contractions in rats (Su et al, 2013). In these experiments, the effect of sacral neuromodulation was not altered by norbinaltorphimine (2.0 mg/kg i.v.)…”

Section: Discussionmentioning

confidence: 80%

Role of µ, κ, and δ Opioid Receptors in Tibial Inhibition of Bladder Overactivity in Cats

Zhang

Slater

Ferroni

et al. 2015

J Pharmacol Exp Ther

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In a-chloralose anesthetized cats, we examined the role of opioid receptor (OR) subtypes (m, k, and d) in tibial nerve stimulation (TNS)-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.25% acetic acid (AA). The sensitivity of TNS inhibition to cumulative i.v. doses of selective OR antagonists (cyprodime for m, nor-binaltorphimine for k, or naltrindole for d ORs) was tested. Naloxone (1 mg/kg, i.v., an antagonist for m, k, and d ORs) was administered at the end of each experiment. AA caused bladder overactivity and significantly (P , 0.01) reduced bladder capacity to 21.1% 6 2.6% of the saline control. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement significantly (P , 0.01) restored bladder capacity to 52.9% 6 3.6% or 57.4% 6 4.6% of control, respectively. Cyprodime (0.3-1.0 mg/kg) completely removed TNS inhibition without changing AA control capacity. Nor-binaltorphimine (3-10 mg/kg) also completely reversed TNS inhibition and significantly (P , 0.05) increased AA control capacity. Naltrindole (1-10 mg/kg) reduced (P , 0.05) TNS inhibition but significantly (P , 0.05) increased AA control capacity. Naloxone (1 mg/kg) had no effect in cyprodime pretreated cats, but it reversed the nor-binaltorphimine-induced increase in bladder capacity and eliminated the TNS inhibition remaining in naltrindole pretreated cats. These results indicate a major role of m and k ORs in TNS inhibition, whereas d ORs play a minor role. Meanwhile, k and d ORs also have an excitatory role in irritation-induced bladder overactivity.

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Section: Discussionmentioning

confidence: 80%

Role of µ, κ, and δ Opioid Receptors in Tibial Inhibition of Bladder Overactivity in Cats

Zhang

Slater

Ferroni

et al. 2015

J Pharmacol Exp Ther

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“…A recent study in rats has also shown that μ ‐opioid receptors are involved in sacral neuromodulation of bladder activity (Su et al. ). In addition, whether these neurotransmitters play different roles in acute‐ and post‐TNS inhibition also needs to be determined.…”

Section: Discussionmentioning

confidence: 99%

Poststimulation inhibition of the micturition reflex induced by tibial nerve stimulation in rats

et al. 2014

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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.

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“…One would assume that output signals would be synchronized if the perfectly matched pulses from right and left SN stimulation are transmitted directly. Therefore enhanced bladder inhibitory effects to bilateral stimulation could be attributed to a polysynaptic reflex at the spinal and supraspinal centers [20]. …”

Section: Discussionmentioning

confidence: 99%

Quantification of effectiveness of bilateral and unilateral neuromodulation in the rat bladder rhythmic contraction model

Nickles

Nelson

2013

BMC Urol

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BackgroundUsing the isovolumetric bladder rhythmic contraction (BRC) model in anesthetized rats, we have quantified the responsiveness to unilateral and bilateral stimulation of the L6 spinal nerve (SN) and characterized the relationship between stimulus intensity and inhibition of the bladder micturition reflex.MethodsA wire electrode was placed under either one or both of the L6 SN roots. A cannula was placed into the bladder via the urethra and the urethra was ligated. Saline infusion induced BRC.ResultsAt motor threshold (Tmot) intensity, SN stimulation of both roots (10 Hz) for 10 min reduced bladder contraction frequency from 0.63 ± 0.04 to 0.17 ± 0.09 contractions per min (26 ± 14% of baseline control; n = 10, p < 0.05). However, the same intensity of unilateral stimulation (n = 15) or sequential stimulation of both SNs (e.g. 5 min per side alternatively for a total of 10 min or 20 min) was less efficacious. The greater sensitivity to bilateral stimulation is not dependent upon precise bilateral timing of the stimulation pulses. Bilateral stimulation also produced both acute and prolonged- inhibition on bladder contractions in a stimulation intensity dependent fashion.ConclusionsUsing the bladder rhythmic contraction model, bilateral stimulation was more effective than unilateral stimulation of the SN. Clinical testing should be conducted to further compare efficacies of unilateral and bilateral stimulation. Bilateral stimulation may allow the use of lower stimulation intensities to achieve higher efficacy for neurostimulation therapies on urinary tract control.

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Role of the endogenous opioid system in modulation of urinary bladder activity by spinal nerve stimulation

Cited by 21 publications

References 26 publications

Role of µ, κ, and δ Opioid Receptors in Tibial Inhibition of Bladder Overactivity in Cats

Role of µ, κ, and δ Opioid Receptors in Tibial Inhibition of Bladder Overactivity in Cats

Poststimulation inhibition of the micturition reflex induced by tibial nerve stimulation in rats

Quantification of effectiveness of bilateral and unilateral neuromodulation in the rat bladder rhythmic contraction model

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