title: Central muscarinic inhibition of lower urinary tract nociception.
abstract: Previous studies indicate cholinergic systems suppress somatic nociception. The present studies determined if cholinergic muscarinic systems suppress visceral nociception, specifically, chemical irritation of the lower urinary tract. Bladders of urethane-anesthetized rats were cannulated through the dome for continuous-infusion cystometrogram recordings. EMG electrodes recorded anal sphincter activity. Infusion of 0.5% acetic acid into the bladder to produce irritation increased bladder activity and anal sphincter activity (i.e. activation of a nociceptive vesicoanal reflex). Oxotremorine (a muscarinic agonist) and (-)butylthio[2.2.2] (a mixed muscarinic agonist/antagonist) dose-dependently inhibited vesicoanal reflex activity. This inhibition was antagonized by atropine (a centrally active muscarinic antagonist) but not by scopolamine methylbromide (a peripherally restricted muscarinic antagonist). Physostigmine (a centrally active cholinesterase inhibitor) also dose-dependently inhibited vesicoanal reflex activity in an atropine-sensitive manner, while neostigmine (a peripherally restricted cholinesterase inhibitor) did not. Atropine alone (i.e. administered without prior administration of muscarinic agonist or cholinesterase inhibitor) produced robust but transient (15 min) increases in vesicoanal activity and bladder activity under conditions of acetic acid infusion into the bladder. Under conditions of saline infusion into the bladder, atropine had the opposite effect on bladder activity (i.e. inhibition). These studies indicate that an endogenous cholinergic muscarinic system can be activated by lower urinary tract irritation to suppress visceral nociception through central nervous system mechanisms.
authors.affiliation: PPD GenuPro, Inc., 3900 Paramount Parkway, Morrisville, NC 27560, USA. karl.thor@genupro.ppdi.com
authors.forename: K B
authors.initials: KB
authors.lastname: Thor
authors.forename: M A
authors.initials: MA
authors.lastname: Muhlhauser
authors.forename: P
authors.initials: P
authors.lastname: Sauerberg
authors.forename: H
authors.initials: H
authors.lastname: Shannon
authors.forename: J P
authors.initials: JP
authors.lastname: Springer
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004576:Electromyography; D005260:Female; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010095:Oxotremorine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013830:Thiadiazoles / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D013830:Thiadiazoles; D014665:Vasodilator Agents; D009388:Neostigmine; D010095:Oxotremorine; D001285:Atropine; C101714:LY 297802; D010830:Physostigmine; D000109:Acetylcholine