title: 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.
abstract: 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.
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis 88040-900, SC, Brazil.
authors.forename: Daniela Tagliari
authors.initials: DT
authors.lastname: Longhi-Balbinot
authors.forename: Evelise Fernandes
authors.initials: EF
authors.lastname: Pietrovski
authors.forename: Vinicius Maria
authors.initials: VM
authors.lastname: Gadotti
authors.forename: Daniel Fernandes
authors.initials: DF
authors.lastname: Martins
authors.forename: Valdir Alves
authors.initials: VA
authors.lastname: Facundo
authors.forename: Adair Roberto Soares
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D017470:Receptors, Glutamate / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects*; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C510987:3beta,6beta,16beta-trihidroxilup-20(29)-ene; D000700:Analgesics; D018690:Excitatory Amino Acid Agonists; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014315:Triterpenes; D018698:Glutamic Acid