Spinal antinociception evoked by the triterpene 3beta, 6beta, 16beta-trihydroxylup-20(29)-ene in mice: evidence for the involvement of the glutamatergic system via NMDA and metabotropic glutamate receptors.

The present study investigated the possible involvement of the glutamatergic and neurokinin systems in the antinociception caused by triterpene 3beta, 6beta, 16beta-trihydroxylup-20(29)-ene (TTHL) in mice. TTHL given by intraperitoneal (i.p., 2.1-65.5micromol/kg), intraplantar (i.pl., 6.5-65.5nmol/paw) or intrathecal (i.t., 21.8-655nmol/site) routes, produced dose-dependent inhibition of glutamate-induced nociception with ID(50) values of 12micromol/kg; 34.2nmol/paw; 233.8nmol/site and inhibitions of 78+/-6; 82+/-4 and 77+/-8%, respectively. I.t. injection of TTHL (6.5-218nmol/site, co-administered) also caused significant and dose-dependent reduction of nociceptive response induced by i.t. injection of glutamate (175nmol/site), with ID(50) value of 54.5nmol/site and inhibition of 51+/-6%. Moreover, TTHL (65.5nmol/site) co-injected by i.t. route with agonist caused marked reduction of nociceptive responses induced by N-methyl-d-aspartate (NMDA, 450pmol/site), (+/-)-1-aminocyclopentane-trans-1,3 dicarboxylic acid (trans-ACPD, 10nmol/site) and substance P (100pmol/site), with inhibitions of 81+/-7; 79+/-7; 81+/-11%, respectively. Conversely, TTHL had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 135pmol/site) and kainic acid (kainate, 110pmol/site)-induced nociception. Moreover, the association of sub-effective doses of TTHL (6.5nmol/site, i.t.) and MK-801(1nmol/site, i.t.; non-competitive NMDA antagonist) or (RS)-MCPG (30nmol/site, i.t.; non-selective group I/group II metabotropic glutamate receptor antagonist) produced a synergic antinociceptive effect in the nociception induced by NMDA or trans-ACPD, respectively. Together, these results provide experimental evidence for the involvement of the glutamatergic system (NMDA and metabotropic glutamate receptors) in the antinociceptive action caused by TTHL in mice.