Baclofen, an agonist at peripheral GABAB receptors, induces antinociception via activation of TEA-sensitive potassium channels.
OBJECTIVE
Central anti-nociceptive actions of baclofen involve activation of K+ channels. Here we assessed what types of K+ channel might participate in the peripheral anti-nociception induced by baclofen.


METHODS
Nociceptive thresholds to mechanical stimulation in rat paws treated with intraplantar prostaglandin E2.(PGE2) to induce hyperalgesia were measured 3 h after PGE2 injection. Other agents were also given by intraplantar injection.


RESULTS
Baclofen elicited a dose-dependent (15 - 240 microg per paw) anti-nociceptive effect. An intermediate dose of baclofen (60 microg) did not produce antinociception in the contralateral paw, showing its peripheral site of action. The GABAB receptor antagonist saclofen (12.5 - 100 microg per paw) antagonized, in a dose-dependent manner, peripheral antinociception induced by baclofen (60 microg), suggesting a specific effect. This antinociceptive action of baclofen was unaffected by bicuculline, GABAA receptor antagonist (80 microg per paw), or by (1,2,5,6 tetrahydropyridin-4-yl) methylphosphinic acid, GABAC receptor antagonist (20 microg per paw). The peripheral antinociception induced by baclofen (60 microg) was reversed, in a dose-dependent manner, by the voltage-dependent K+ channel blockers tetraethylammonium (7.5 - 30 microg per paw) and 4-aminopyridine (2.5 - 10 microg per paw). The blockers of other K+ channels, glibenclamide (160 microg), tolbutamide (320 microg), charybdotoxin (2 microg), dequalinium (50 microg) and caesium (500 microg) had no effect.


CONCLUSIONS
This study provides evidence that the peripheral antinociceptive effect of the GABAB receptor agonist baclofen results from the activation of tetraethylammonium-sensitive K+ channels. Other K+ channels appear not to be involved.
Reis
G M L
GM
Department of Pharmacology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil.
Duarte
I D G
ID
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D003868:Dequalinium / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D000700:Analgesics; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D015221:Potassium Channels; D018999:Charybdotoxin; D002586:Cesium; D019789:Tetraethylammonium; D014044:Tolbutamide; D003868:Dequalinium; D001418:Baclofen; C080629:saclofen; D005905:Glyburide; D001640:Bicuculline