title: Evidence for the involvement of metabotropic glutamatergic, neurokinin 1 receptor pathways and protein kinase C in the antinociceptive effect of dipyrone in mice.
abstract: This study aimed to investigate further the mechanisms involved in the antinociception caused by dipyrone, given by intraperitoneal (i.p.) or intrathecal (i.t.) routes. The intraperitoneal administration of dipyrone to mice 30 min prior resulted in a significant and dose-related inhibition of the biting responses induced by i.t. injection of glutamate, trans-ACPD or substance P (SP). In addition, dipyrone given by i.t. route, 15 min before glutamate, trans-ACPD or SP, also produced a significant reduction in their nociceptive effects. In addition, dipyrone given by i.t. route, 15 min before glutamate, trans-ACPD or SP, also produced a significant reduction in their nociceptive effects. Dipyrone, given either systemically (i.p.) or by i.t. route also caused a dose-dependent inhibition of phorbol myristate acetate (PMA)-induced nociception. Given by systemic route, dipyrone inhibited PMA-induced paw oedema formation. Collectively, these results extend previous data from our group indicating that glutamatergic-mediated pain responses, specifically those mediated by metabotropic receptor subtype, together with inhibition of neurokinin NK(1)-mediated response, account for the antinociceptive action of dipyrone in mice. Furthermore, we have also produced experimental evidence indicating that the activation of the protein kinase C-dependent pathway plays a role in the dipyrone antinociceptive action.
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, Florianópolis, SC 88015-420, Brazil.
authors.forename: Joice S
authors.initials: JS
authors.lastname: Siebel
authors.forename: Alessandra
authors.initials: A
authors.lastname: Beirith
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D004177:Dipyrone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020536:Enzyme Activators / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011493:Protein Kinase C / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology
chemical_list: D020536:Enzyme Activators; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D018040:Receptors, Neurokinin-1; D013373:Substance P; D004177:Dipyrone; D011493:Protein Kinase C