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