Spinal mechanisms of antinociceptive effect caused by oral administration of bis-selenide in mice

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 α-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-α (TNF-α; 0.1 pg/site), interleukin-1β (IL-1β; 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 ID50 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 Ca2+-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.