title: Spinal mechanisms of antinociceptive action caused by diphenyl diselenide.
abstract: The present study was designed to investigate further the mechanisms involved in the antinociception caused by diphenyl diselenide in behavioral model of pain in mice. Diphenyl diselenide (1-100 mg/kg), given orally, produced significant inhibition of the biting behavior induced by intrathecal (i.t.) injection of glutamate (175 nmol/site) and N-methyl-d-aspartate (NMDA; 450 pmol/site), with mean ID(50) values of 45.92 (39.74-60.4) and 55.77 (36.52-77.5) mg/kg respectively. However, diphenyl diselenide completely failed to affect the nociception induced by alpha-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA; 135 pmol/site), (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 50 nmol/site) and kainate (110 pmol/site). This compound also reduced the nociceptive response induced by substance P (SP) (135 ng/site, i.t.), interleukin 1beta (IL-1beta; 1 pg/site), tumor necrosis factor-alpha (TNF-alpha; 0.1 pg/site), bradykinin (BK; 0.1 microg/site) and capsaicin (30 ng/site) with mean ID(50) values of 16.22, 7.06, 6.06, 4.18 and 7.90 mg/kg, respectively. Together, these results indicate that diphenyl diselenide produced antinociception at spinal sites, with a possible interaction with glutamatergic pathways, more specifically via interaction with NMDA receptors, peptidergic or vanilloid systems.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Lucielli
authors.initials: L
authors.lastname: Savegnago
authors.forename: Larissa G
authors.initials: LG
authors.lastname: Pinto
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Jesse
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001555:Benzene Derivatives / Q000627:therapeutic use*; D001920:Bradykinin; D002211:Capsaicin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists; D020128:Inhibitory Concentration 50; D053583:Interleukin-1beta; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D010147:Pain Measurement; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013373:Substance P; D014409:Tumor Necrosis Factor-alpha
chemical_list: D001555:Benzene Derivatives; D018690:Excitatory Amino Acid Agonists; D053583:Interleukin-1beta; D016566:Organoselenium Compounds; D014409:Tumor Necrosis Factor-alpha; C061132:diphenyldiselenide; D013373:Substance P; D002211:Capsaicin; D001920:Bradykinin