Substances derived from plants play an important role in the development of new
analgesic drugs, among them,
triterpenoids. The connection between the participation of
L-arginine/NO/cGMP pathway and the activation of
ATP-sensitive K(+)
channels (KATP) has been established on the peripheral antinociception induced by various drugs. The study assessed the involvement of
L-arginine/NO/cGMP/KATP pathway in the antinociceptive effect induced by
tingenone, from Maytenus imbricata, against the
hyperalgesia evoked by
prostaglandin E2 (
PGE2) in peripheral pathway. The paw pressure test was used, with
hyperalgesia induced by intraplantar injection of
PGE2 (2 μg).
Tingenone (200 µg/paw) administered into the right hind paw induced a local antinociceptive effect, that was antagonized by l-
NOArg, nonselective
nitric oxide synthase (NOS) inhibitor and by L-NPA, selective neuronal NOS (nNOS) inhibitor. The
L-NIO, selective inhibitor of endothelial (eNOS), and the L-NIL, selective inhibitor of inducible (iNOS), did not alter the peripheral antinociceptive effect of the
tingenone. The ODQ, selective
soluble guanylyl cyclase inhibitor, prevented the antinociceptive effect of
tingenone, and
zaprinast, inhibitor of the
phosphodiesterase that is cyclic
guanosine monophosphate (cGMP) specific, intensified the peripheral antinociceptive effect of the smaller dose of
tingenone.
Glibenclamide,
ATP-sensitive K(+)
channels (KATP) blocker, but not
tetraethylammonium chloride, voltage-dependent K(+) channel blocker;
dequalinium dichloride, blocker of the small conductance Ca(2+)-activated K(+) channel, and
paxilline, a potent blocker of high-conductance Ca(2+)-activated K(+) channels, respectively, prevented the peripheral antinociceptive effect of
tingenone. The results demonstrate that
tingenone induced a peripheral antinociceptive effect by
L-arginine/NO/cGMP/KATP pathway activation, with potential for a new
analgesic drug.