Baclofen, an agonist at peripheral GABAB receptors, induces antinociception via activation of TEA-sensitive potassium channels

Br J Pharmacol. 2006 Nov;149(6):733-9. doi: 10.1038/sj.bjp.0706898. Epub 2006 Oct 3.


Background and purpose: 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.

Experimental approach: 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.

Key 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 and implications: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Baclofen / analogs & derivatives
  • Baclofen / pharmacology*
  • Bicuculline / pharmacology
  • Cesium / pharmacology
  • Charybdotoxin / pharmacology
  • Dequalinium / pharmacology
  • GABA Agonists / pharmacology*
  • GABA-B Receptor Agonists*
  • Glyburide / pharmacology
  • Male
  • Potassium Channels / drug effects*
  • Rats
  • Rats, Wistar
  • Tetraethylammonium / pharmacology*
  • Tolbutamide / pharmacology


  • Analgesics
  • GABA Agonists
  • GABA-B Receptor Agonists
  • Potassium Channels
  • Charybdotoxin
  • Cesium
  • Tetraethylammonium
  • Tolbutamide
  • Dequalinium
  • Baclofen
  • saclofen
  • Glyburide
  • Bicuculline