Spinal mechanisms of antinociceptive action caused by diphenyl diselenide.
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.
Savegnago
Lucielli
L
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.
Pinto
Larissa G
LG
Jesse
Cristiano R
CR
Rocha
João B T
JB
Nogueira
Cristina W
CW
Zeni
Gilson
G
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
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