title: Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats.
abstract: 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.
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors: Jeremy N
authors: JN
authors: Reese
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors: Marc J
authors: MJ
authors: Rogers
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, The Second Hospital, Shandong University, Jinan, People's Republic of China; and.
authors: Zhiying
authors: Z
authors: Xiao
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors: Bing
authors: B
authors: Shen
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors: Jicheng
authors: J
authors: Wang
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors: Zeyad
authors: Z
authors: Schwen
authors: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: James R
authors: JR
authors: Roppolo
authors: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: William C
authors: WC
authors: de Groat
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania cftai@pitt.edu.
authors: Changfeng
authors: C
authors: Tai
mesh_terms: D019342:Acetic Acid; D000200:Action Potentials; D000818:Animals; D002415:Cats; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000294:innervation*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D060525:Pudendal Nerve / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology; D013127:Spinal Nerves / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013844:Thiazoles / Q000494:pharmacology; D013904:Thoracic Vertebrae; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation*; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D014563:Urodynamics
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles; D019342:Acetic Acid
keywords: bladder; cat; glutamate; neuromodulation; pudendal