title: Role of spinal GABAA receptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats.
abstract: Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA; 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce nonnociceptive bladder activity. To modulate the bladder reflex, pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly (P < 0.01) reduced bladder capacity to 34.3 ± 7.1% of the saline control capacity, while PNS at 2T and 4T significantly (P < 0.01) increased AA bladder capacity to 84.0 ± 7.8 and 93.2 ± 15.0%, respectively, of the saline control. Picrotoxin (0.4 mg it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly (P < 0.05) reduced 2T PNS inhibition at low doses (0.01-0.1 mg/kg). During saline cystometry, PNS significantly (P < 0.01) increased bladder capacity to 147.0 ± 7.6% at 2T and 172.7 ± 8.9% at 4T of control capacity, and picrotoxin (0.4 mg it or 0.03-0.3 mg/kg iv) also significantly (P < 0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and nonnociceptive reflex bladder activities and in PNS inhibition of these activities.
authors: Dept. of Urology, Univ. of Pittsburgh, 700 Kaufmann Bldg., Pittsburgh, PA 15213. cftai@pitt.edu.
authors: Zhiying
authors: Z
authors: Xiao
authors: Jeremy
authors: J
authors: Reese
authors: Zeyad
authors: Z
authors: Schwen
authors: Bing
authors: B
authors: Shen
authors: Jicheng
authors: J
authors: Wang
authors: James R
authors: JR
authors: Roppolo
authors: William C
authors: WC
authors: de Groat
authors: Changfeng
authors: C
authors: Tai
mesh_terms: D019342:Acetic Acid; D000818:Animals; D002415:Cats; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D059226:Nociceptive Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D009619:Nociceptors / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects; D060525:Pudendal Nerve / Q000187:drug effects / Q000503:physiopathology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects; D013127:Spinal Nerves / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001743:Urinary Bladder / Q000294:innervation*; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D018756:GABA Antagonists; D011963:Receptors, GABA-A; D019342:Acetic Acid
keywords: GABAA receptor; cat; neuromodulation; urinary bladder