title: A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation.
abstract: Electrical stimulation of pudendal afferents can inhibit bladder contractions and increase bladder capacity. Recent results suggest that stimulation-evoked bladder inhibition is mediated by a mechanism other than activation of sympathetic bladder efferents in the hypogastric nerve, generating α-adrenergic receptor-mediated inhibition at the vesical ganglia and/or β-adrenergic receptor-mediated direct inhibition of the detrusor muscle. We investigated several inhibitory neurotransmitters that may instead be necessary for stimulation-evoked inhibition and found that intravenous picrotoxin, a noncompetitive GABAA antagonist, significantly and reversibly blocked pudendal afferent stimulation-evoked inhibition of bladder contractions in a dose-dependent manner. Similarly, intravenous picrotoxin also blocked pudendal afferent stimulation-evoked inhibition of nociceptive bladder contractions evoked by acetic acid infusion. Furthermore, intrathecal administration of picrotoxin at the lumbosacral spinal cord also blocked bladder inhibition by pudendal afferent stimulation. On the other hand, glycinergic, adrenergic, or opioidergic mechanisms were not necessary for bladder inhibition evoked by pudendal afferent stimulation. These results identify a lumbosacral spinal GABAergic mechanism of bladder inhibition evoked by pudendal afferent stimulation.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina;
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: McGee
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina;
authors.forename: Zachary C
authors.initials: ZC
authors.lastname: Danziger
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina;
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Bamford
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina; Department of Neurobiology, Duke University, Durham, North Carolina; Department of Surgery, Duke University, Durham, North Carolina; and Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina warren.grill@duke.edu.
authors.forename: Warren M
authors.initials: WM
authors.lastname: Grill
mesh_terms: D019342:Acetic Acid / Q000037:antagonists & inhibitors; D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009475:Neurons, Afferent / Q000502:physiology; D010413:Penis / Q000294:innervation; D010852:Picrotoxin / Q000494:pharmacology; D060525:Pudendal Nerve / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
chemical_list: D019342:Acetic Acid; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D011943:Receptors, Adrenergic, beta
keywords: GABA; bladder inhibition; dorsal nerve of the penis; electrical stimulation; picrotoxin; pudendal nerve