Inhibitory effect of intrathecal glycine on the micturition reflex in normal and spinal cord injury rats

Miyazato, Minoru; Sugaya, Kimio; Nishijima, Saori; Ashitomi, Katsuhiro; Hatano, Tadashi; Ogawa, Yoshihide

doi:10.1016/s0014-4886(03)00175-4

Cited by 56 publications

(73 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[3][4] GABA is another important inhibitory neurotransmitter in the central nervous system. 5 GABA is synthesized from glutamate by GAD, 5 and is known to have an important role in the inhibitory regulation of micturition in spinal intact rats.…”

Section: Introductionmentioning

confidence: 99%

GABA Receptor Activation in the Lumbosacral Spinal Cord Decreases Detrusor Overactivity in Spinal Cord Injured Rats

et al. 2008

Self Cite

View full text Add to dashboard Cite

Purpose-We investigated the effects of intrathecal application of GABA A and GABA B receptor agonists on detrusor overactivity in spinal cord injured rats.Materials and Methods-Adult female Sprague-Dawley rats were used. At 4 weeks after Th9-10 spinal cord transection, awake cystometry and recordings of external urethral sphincter electromyogram were performed to examine the effect of intrathecal application of GABA A and GABA B agonists (muscimol and baclofen, respectively) or GABA A and GABA B antagonists (bicuculline and saclofen, respectively) at the level of L6-S1 spinal cord. Expression of glutamate decarboxylase 67 mRNA in the L6-S1 spinal cord and dorsal root ganglia was also assessed.Results-Both muscimol and baclofen produced a dose-dependent inhibition of the number (51-73% decrease) and amplitude (35-93% decrease) of nonvoiding bladder contractions, and a decrease in micturition pressure. The effects of muscimol and baclofen were antagonized by bicuculline and saclofen, respectively. Bursting activity of external urethral sphincter electromyogram was inhibited corresponding to the inhibition of bladder activity by muscimol and baclofen. Glutamate decarboxylase 67 mRNA levels in the spinal cord and dorsal root ganglia was decreased (55% and 84%, respectively) after spinal cord transection.Conclusions-These results indicate that GABA A and GABA B receptor activation in the spinal cord inhibits detrusor overactiivty. The reduction in glutamate decarboxylase 67 mRNA suggests hypofunction of GABAergic inhibitory mechanisms in the spinal cord. Therefore, stimulation of spinal GABAergic mechanisms could be effective for the treatment of detrusor overactivity after spinal cord injury.

show abstract

Section: Introductionmentioning

confidence: 99%

GABA Receptor Activation in the Lumbosacral Spinal Cord Decreases Detrusor Overactivity in Spinal Cord Injured Rats

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the threshold dose of glycine on the micturition reflex was lower in urethane-anesthetized rats than in conscious rats, and this difference may have been due to the depth of anesthesia. A previous study demonstrated that intrathecal injection of glycine prolongs the interval and decreases the amplitude of bladder contraction in normal rats, suggesting that a spinal glycinergic mechanism inhibits the spinal afferent and efferent limbs of the spinobulbospinal micturition reflex pathway (16). Miyazato et al (18) demonstrated that the inhibitory effects of intravenous glycine on the micturition reflex are abolished by intrathecal strychnine, a selective glycine receptor antagonist, and that isovolumetric bladder contractions due to intravesical infusion of 1% glycine are not different from those using saline.…”

Section: Discussionmentioning

confidence: 97%

“…We therefore focused on low-dose combination therapy for the purpose of reducing their toxicity in normal, conscious rats. Glycine, a major inhibitory neurotransmitter, plays a role in the control of spinal nociceptive processing (29) and bladder function in both physiological and pathological conditions (16,19). Previous studies have suggested that spinal and serum glycine levels in rats after partial bladder outlet obstruction (17) and in humans with BPH (19) decrease, and thereby may partly cause detrusor overactivity.…”

Section: Effect Of Oral Administration Of Loxoprofen On Voiding Behaviormentioning

confidence: 99%

“…In rats under urethane anesthesia, systemic or intrathecal administration of glycine inhibits the micturition reflex in both intact and spinal cord-injured rats. This effect relies on inhibitory mechanisms that modulate the spinobulbospinal and spinal micturition reflex pathways at the level of the lumbosacral cord (16). Although intrathecal injection of a glutamate receptor antagonist decreases glutamate and glycine levels in the lumbosacral cord in urethaneanesthetized rats (7), different effects of glutamate receptor antagonists on the micturition reflex between conscious and urethane-anesthetized rats have been reported (28).…”

Section: Effect Of Oral Administration Of Loxoprofen On Voiding Behaviormentioning

confidence: 99%

See 1 more Smart Citation

Synergistic effects of loxoprofen and glycine on the micturition reflex in consciousrats

et al. 2014

View full text Add to dashboard Cite

We examined the inhibitory effects of loxoprofen, a cyclooxygenase inhibitor, and glycine, a major inhibitory neurotransmitter, on the micturition reflex in conscious rats and hypothesized that these drugs would interact synergistically to inhibit micturition. Voiding behaviors were assessed using a metabolic cage. Oral loxoprofen decreased the urinary frequency, and only a high dose (10 mg/kg) significantly reduced the voided volume. With cystometry, intravenous loxoprofen (0.1-3 mg/kg) and glycine (30 and 100 mg/kg) prolonged the intercontraction intervals (ICI) in a dose-dependent manner, but did not change the maximum voiding pressure (MVP) in conscious rats. The combination of loxoprofen (3 mg/kg) and glycine (100 mg/kg) strongly prolonged the ICI more than with either drug alone. The lowest dose of loxoprofen (0.1 mg/kg) and glycine (30 mg/kg) did not affect either the ICI or the MVP, but their combination resulted in a significant increase in the ICI. These results suggest that the combined administration of loxoprofen and glycine produced a synergistic inhibitory effect on the micturition reflex.Bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH) induces various bladder dysfunctions. Nocturia in patients with BPH is one of the most bothersome symptoms of the disease. The presence of nocturia disrupts sleep, leading to daytime somnolence, depressive symptoms, cognitive dysfunction, and reduction in quality of life (10). Although nocturia in patients with BPH is commonly treated with α 1 -blockers and/or 5α-reductase inhibitors, using these drugs to reduce nocturia is not effective in many cases. Clinical reports have been published indicating that loxoprofen, a non-steroidal anti-inflammatory drug (NSAID), reduces not only pain and inflammation but also nocturia in patients with BPH (6,22).Other NSAIDs such as indomethacin also reduce the frequency of voiding and decrease the urine volume in patients with enuresis (1). NSAIDs including loxoprofen prevent prostaglandin (PG) synthesis by inhibiting the cyclooxygenase pathway. PGs, in particular PGE 2 , play an important role in regulating bladder function, and intravesical infusion of PGE 2 stimulates the micturition reflex by activating capsaicin-sensitive afferent nerves, leading to bladder overactivity in rats and humans (13,14,24). In addition, the urinary PGE 2 level has been reported to increase in patients with lower urinary tract obstruction (4). Previous studies have shown that NSAIDs decrease urinary frequency and increase bladder capacity in both normal and cystitis rats under urethane anesthesia (26,27). We also reported that loxoprofen inhibits enhancement of the micturition reflex after acetic acid-induced inflammation in conscious rats (24). However, the inhibitory effect of loxoprofen on the micturition reflex in normal, conscious states has not been fully examined. In addition, long-term use of NSAIDs is not recommended

show abstract

“…In addition, recent studies revealed that the level of glycine in the spinal cord is decreased by approximately 50% in rats with DO induced by chronic spinal cord injury, compared with spinal intact rats (437,438) and that dietary supplement of glycine can restore bladder function along with an increase in the serum level of glycine in spinal cord injured rats (438). The level of glutamic acid decarboxylase (GAD), the GABA synthetic enzyme, is also reduced in the spinal cord and lumbosacral DRG in spinal cord-injured rats with DO (433) and sphincter-detrusor dyssynergia (DSD) (434), and both impaired functions are suppressed by intrathecal application of GABA A or GABA B receptor agonists (433,434).…”

Section: Neurotransmitters In Central Pathways Controlling Micturitionmentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

2009

Encyclopedia of Neuroscience

View full text Add to dashboard Cite

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.

show abstract

Inhibitory effect of intrathecal glycine on the micturition reflex in normal and spinal cord injury rats

Cited by 56 publications

References 33 publications

GABA Receptor Activation in the Lumbosacral Spinal Cord Decreases Detrusor Overactivity in Spinal Cord Injured Rats

GABA Receptor Activation in the Lumbosacral Spinal Cord Decreases Detrusor Overactivity in Spinal Cord Injured Rats

Synergistic effects of loxoprofen and glycine on the micturition reflex in consciousrats

Neural Control of the Lower Urinary Tract

Contact Info

Product

Resources

About