Glutamatergic Mechanisms Involved in Bladder Overactivity and Pudendal Neuromodulation in Cats

Abstract

The involvement of ionotropic glutamate receptors in bladder overactivity and pudendal neuromodulation was determined in a-chloralose anesthetized cats by intravenously administering MK801 (a NMDA receptor antagonist) or CP465022 (an AMPA receptor antagonist). Infusion of 0.5% acetic acid (AA) into the bladder produced bladder overactivity. In the first group of 5 cats, bladder capacity was significantly (P , 0.05) reduced to 55.3610.0% of saline control by AA irritation. Pudendal nerve stimulation (PNS) significantly (P , 0.05) increased bladder capacity to 106.8 6 15.0% and 106.7 6 13.3% of saline control at 2T and 4T intensity, respectively. T is threshold intensity for inducing anal twitching. MK801 at 0.3 mg/kg prevented the increase in capacity by 2T or 4T PNS. In the second group of 5 cats, bladder capacity was significantly (P , 0.05) reduced to 49.0 6 7.5% of saline control by AA irritation. It was then significantly (P , 0.05) increased to 80.8613.5% and 79.06 14.0% of saline control by 2T and 4T PNS, respectively. CP465022 at 0.03-1 mg/kg prevented the increase in capacity by 2T PNS and at 0.3-1 mg/kg prevented the increase in capacity by 4T PNS. In both groups, MK801 at 0.3 mg/kg and CP465022 at 1 mg/kg significantly (P , 0.05) increased the prestimulation bladder capacity (about 80% and 20%, respectively) and reduced the amplitude of bladder contractions (about 30 and 20 cmH 2 O, respectively). These results indicate that NMDA and AMPA glutamate receptors are important for PNS to inhibit bladder overactivity and that tonic activation of these receptors also contributes to the bladder overactivity induced by AA irritation.

Suppression of Urinary Voiding by Conditional High Frequency Stimulation of the Pelvic Nerve in Conscious Rats

“…In the clinical setting, sacral nerve stimulation is the procedure offered most commonly in cases that are refractory to current pharmacological and chemodenervation approaches, although other targets are also being used (see Janssen et al, 2017 for a recent review). In animal studies the net has been cast wider and there are several indications from studies in anesthetized cats and rats that stimulation of the tibial, saphenous, pudendal, dorsal penile, dorsal clitoral, and pelvic nerves all have the potential to modulate voiding ( Snellings and Grill, 2012 ; Su et al, 2012a , b ; Kovacevic and Yoo, 2014 ; Jen et al, 2016 ; Langdale et al, 2017 ; Moazzam and Yoo, 2017 ; Uy et al, 2017 ). In these studies, nerve stimulation was able to inhibit or reduce the frequency of voiding, or to decrease the rate of micturition-like contractions produced under isovolumetric conditions by producing an increase in bladder capacity.…”

Gentle Perineal Skin Stimulation for Control of Nocturia

“…In the CMG model, peripheral nerve stimulation to anesthetized animals prolonged the latency of urination, indicating an increased volume threshold of the micturition reflex (Su et al, ; Choudhary et al, ; Jiang et al, ; Kadow et al, ; Rogers et al, ; Bandari et al, ; Bansal et al, ; Fuller et al, ; Uy et al, ; Zhang et al, ). In the RMC model, peripheral nerve stimulation abolished periodic intravesical pressure changes, reflecting suppression of the micturition reflex at a volume that was previously supra‐threshold (Su et al, ; Kovacevic and Yoo, ; Su et al, ; Onda et al, ; Ren et al, ).…”

“…In studies examining the effects of peripheral nerve activation by electrical stimulation on urinary bladder functions, stimulation is commonly applied to the tibial nerve, pudendal nerves, or the sacral nerves (Su et al, 2013a(Su et al, , 2013b(Su et al, , 2015Kovacevic and Yoo, 2015;Choudhary et al, 2016;Jiang et al, 2016;Kadow et al, 2016;Onda et al, 2016;Ren et al, 2016;Rogers et al, 2016;Bandari et al, 2017;Bansal et al, 2017;Fuller et al, 2017;Uy et al, 2017;Zhang et al, 2017). Hence, somatic afferents sending sensory inputs to spinal levels near pelvic nerve efferent outputs innervating the bladder are generally targeted for stimulation.…”

The projection of anorectal afferents to spinal cord and effect of sacral neuromodulation on dorsal horn neurons which receive such input in the rat

“…In other models of visceral hypersensitivity, for example bladder incontinence models, the following examples of neuronal plasticity have been observed. Antagonists for opioids, β‐adrenoceptors, metabotropic glutamate, ionotropic glutamate (NMDA and AMPA), GABA, and glycine receptors have been tested in a cat model; if an antagonist impaired the inhibition of bladder voiding by 5 Hz SNM, the neurotransmitter was postulated to be part of the SNM effect . Only one study to date has examined the interaction between neurotransmitter antagonists and effects of SNM in rats .…”

“…Antagonists for opioids, β-adrenoceptors, metabotropic glutamate, ionotropic glutamate (NMDA and AMPA), GABA, and glycine receptors have been tested in a cat model; if an antagonist impaired the inhibition of bladder voiding by 5 Hz SNM, the neurotransmitter was postulated to be part of the SNM effect. [6][7][8][9] Only one study to date has examined the interaction between neurotransmitter antagonists and effects of SNM in rats. 10 In rats with chronically hyperactive bladder, SNM transiently abolished bladder contractions.…”