title: GABAergic modulation of nociceptive threshold: effects of THIP and bicuculline microinjected in the ventral medulla of the rat.
abstract: Neurons of the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (NGCp alpha) have been implicated in the regulation of nociceptive threshold and production of antinociception. Previous studies have shown that the activity of these neurons is modulated by noradrenergic, cholinergic and serotonergic afferents. The present study examined whether these neurons are additionally subject to regulation by a GABAergic input. Microinjection of the GABAA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; 0.3 or 1.0 microgram) in the NRM or NGCp alpha significantly decreased tail flick latency (TFL) and increased responsiveness to noxious pinch. Hot plate latency (HPL) was not affected by microinjection of 0.3 microgram THIP. Although HPL was increased after microinjection of 1.0 microgram THIP, this effect may reflect motoric disturbances. In contrast to the hyperalgesia produced by THIP, microinjection of the GABAA receptor antagonist bicuculline methiodide (0.04 or 0.1 microgram) produced a small, but significant increase in TFL. Responsiveness to noxious pinch and HPL were not affected by either dose. These findings indicate that neurons of the NRM or NGCp alpha involved in the regulation of nociceptive threshold are subject to an inhibitory GABAergic input mediated by a GABAA receptor. However, in contrast to previously described inhibitory inputs, the GABAergic influence does not appear to be tonically active to a substantial extent in the unanesthetized rat.
authors.affiliation: Central Nervous System Diseases Research, G.D. Searle & Company, Skokie, IL 60077.
authors.forename: E J
authors.initials: EJ
authors.lastname: Drower
authors.forename: D L
authors.initials: DL
authors.lastname: Hammond
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D010080:Oxazoles / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D012684:Sensory Thresholds / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D007555:Isoxazoles; D010080:Oxazoles; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; C015542:gaboxadol; D001640:Bicuculline