The involvement of K+ channels and G(i/o) protein in the antinociceptive action of the gallic acid ethyl ester

The anti-hyperalgesic action, antinociception, and also the possible mechan isms involved in the action of gallic acid ethyl ester (GAEE) isolated from the aerial part of Phyllanthus urinaria, have been investigated in differe nt models of chemical, mechanical and thermal nociception in mice and rats. GAEE given by intraperitoneal (i.p.), oral (p.o.), intrathecal (i.t.) or b y intracerebroventricular (i.c.v.) routes produced dose-related antinocicep tion when assessed against chemical nociception in mice. GAEE significantly inhibited the hyperalgesia induced by bradykinin or substance P in rat paw , but did not affect the hyperalgesia caused by carrageenan or prostaglandi n E-2. Furthermore, GAEE, in contrast to morphine, was completely ineffecti ve in the hot-plate test in mice. The antinociception produced by GAEE (i.p .) in the formalin test was significantly reversed by i.c.v. treatment of a nimals with pertussis toxin and by i.t. administration of K+ channel blocke rs such as apamin, charybdotoxin or glibenclamide, but not by tetraethylamm onium. In contrast, GAEE (i.p.) antinociception was unaffected by i.p. trea tment of animals with naloxone or by nitric oxide precursor, L-arginine, an d this action was not secondary to its anti-inflammatory effect, nor was it associated with non-specific effects such as muscle relaxation or sedation . Thus, GAEE produces dose-dependent and pronounced systemic, spinal and su praspinal antinociception in mice, probably via activation of K+ channels a nd by a G(i/o) pertussis toxin-sensitive mechanism. (C) 1999 Elsevier Scien ce B.V. All rights reserved.