title: Spinal mechanisms of antinociceptive effect caused by oral administration of bis-selenide in mice.
abstract: The present study was designed to investigate further the mechanisms involved in the antinociception caused by bis-selenide in behavioral model of pain in mice. Bis-selenide (5-50 mg/kg), given orally, produced significant inhibition of the antinociceptive behavior induced by intrathecal (i.t.) injection of glutamate (175 nmol/site), kainate (110 pmol/site) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 50 nmol/site) and the maximal inhibitions observed were 57+/-5, 46+/-7 and 73+/-3%, respectively. Bis-selenide failed to affect the nociception induced by alpha-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA; 135 pmol/site) and N-methyl-d-aspartate (NMDA; 450 pmol/site). This compound also reduced the nociceptive response induced by tumor necrosis factor-alpha (TNF-alpha; 0.1 pg/site), interleukin-1beta (IL-1beta; 1 pg/site), substance P (SP) (135 ng/site, i.t.) and capsaicin (30 ng/site) and the inhibitions observed were 81+/-3%, 88+/-1%, 77+/-3 and 67+/-3, respectively. The oral administration of bis-selenide (25-50 mg/kg) in mice caused a significant increase in the reaction time to thermal stimuli in the hot plate test and the mean ID(50) value (and the 95% confidence limits) was 20.37 (15.00-25.74) mg/kg. The antinociceptive effect caused by bis-selenide (50 mg/kg, p.o.) on the hot plate test in mice was reversed by intrathecal (i.t.) injection of some K(+) channel blockers such as tetraethylammonium (TEA, non-selective voltage-dependent K(+) channel inhibitor) and glibenclamide (ATP-sensitive K(+) channel inhibitor), but not apamin and charybdotoxin (large- and small-conductance Ca(2+)-activated K(+) channel inhibitors, respectively). Together, these results indicate that bis-selenide produces antinociception at spinal sites through the activation of ATP-sensitive and voltage-gated K(+) channels and interaction with kainate and trans-ACDP receptors as well as vanilloid and neuropeptide receptors and pro-inflammatory cytokines.
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. criswn@quimica.ufsm.br
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Jesse
authors.forename: Lucielli
authors.initials: L
authors.lastname: Savegnago
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D007278:Injections, Spinal; D051379:Mice; D015394:Molecular Structure; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000700:Analgesics; D002211:Capsaicin; D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D016566:Organoselenium Compounds; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; C533977:(Z)-2,3-bis(4-chlorophenylselanyl)prop-2-en-1-ol; C073111:metabotropic quisqualate receptor