scholarly journals Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats

2015 ◽  
Vol 308 (8) ◽  
pp. F832-F838 ◽  
Author(s):  
Jeremy N. Reese ◽  
Marc J. Rogers ◽  
Zhiying Xiao ◽  
Bing Shen ◽  
Jicheng Wang ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Bladder Capacity ◽  
Spinal Reflex ◽  
Saline Control ◽  
Metabotropic Glutamate Receptor 5 ◽  
Contraction Amplitude ◽  
Metabotropic Glutamate ◽  
Bladder Contraction ◽  
C Fiber

This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (<50 cmH2O) and short duration (<20 s) at a smaller bladder capacity ∼80% of saline control capacity. PNS significantly ( P < 0.01) increased bladder capacity from 85.5 ± 10.1 to 137.3 ± 14.1 or 148.2 ± 11.2% at 2T or 4T stimulation, respectively, where T is the threshold intensity for PNS to induce anal twitch. MTEP {3-[(2-methyl-4-thiazolyl)ethynyl]pyridine; 3 mg/kg iv, a selective mGluR5 antagonist} completely removed the PNS inhibition and significantly ( P < 0.05) increased bladder capacity from 71.8 ± 9.9 to 94.0 ± 13.9% of saline control, but it did not change the bladder contraction amplitude. After propranolol (3 mg/kg iv, a β1/β2-adrenergic receptor antagonist) treatment, PNS inhibition remained but MTEP significantly ( P < 0.05) reduced the bladder contraction amplitude from 18.6 ± 2.1 to 6.6 ± 1.2 cmH2O and eliminated PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly ( P < 0.05) reduced the bladder contraction amplitude from 20.9 ± 3.2 to 8.1 ± 1.5 cmH2O on average demonstrating that spinal reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex.

The role of metabotropic glutamate receptor 5 in developmental lead neurotoxicity

2009 ◽  
Vol 191 (2-3) ◽  
pp. 223-230 ◽  
Author(s):  
Jian Xu ◽  
Chong-huai Yan ◽  
Bo Yang ◽  
Han-fang Xie ◽  
Xiang-yu Zou ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate

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

2019 ◽  
Vol 316 (4) ◽  
pp. F703-F711 ◽  
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.

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

2015 ◽  
Vol 308 (1) ◽  
pp. R42-R49 ◽  
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.

scholarly journals The role of the metabotropic glutamate receptor 5 in nicotine addiction

CNS Spectrums ◽  
2020 ◽  
pp. 1-6
Author(s):  
Funda Akkus ◽  
Sylvia Terbeck ◽  
Connor J. Haggarty ◽  
Valerie Treyer ◽  
Janan J. Dietrich ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Clinical Studies ◽  
Metabotropic Glutamate Receptor ◽  
Therapeutic Potential ◽  
Nicotine Addiction ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate ◽  
Nicotine Abuse ◽  
Preclinical And Clinical Studies

Abstract This review summarizes the evidence for the potential involvement of metabotropic glutamate receptor 5 (mGluR5) in the development of nicotine addiction. Nicotine is consumed worldwide and is highly addictive. Previous research has extensively investigated the role of dopamine in association with reward learning and addiction, which has provided strong evidence for the involvement of dopaminergic neuronal circuitry in nicotine addiction. More recently, researchers focused on glutamatergic transmission after nicotine abuse, and its involvement in the reinforcing and rewarding effects of nicotine addiction. A number of robust preclinical and clinical studies have shown mGluR5 signaling as a facilitating mechanism of nicotine addiction and nicotine withdrawal. Specifically, clinical studies have illustrated lower cortical mGluR5 density in smokers compared to nonsmokers in the human brain. In addition, mGluR5 might selectively regulate craving and withdrawal. This suggests that mGluR5 could be a key receptor in the development of nicotine addiction and therefore clinical trials to examine the therapeutic potential of mGluR5 agents could help to contribute to reduce nicotine addiction in society.

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