BACKGROUND: The study hypothesizes that @entity3810 ( @entity3727 ) releases opioid peptide in the brain stem, which results in inhibition of @entity1246 -mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of @entity1063 , which inhibits nociceptive processing through direct activation of alpha2 adrenoceptor and indirect activation of GABAergic neurons through alpha1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of @entity3727 in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of @entity1363 , a @entity1246 -mimetic agent, on @entity3727 -induced antinociceptive effect. METHODS: Adult male Fischer @entity35 were administered @entity6341 ( @entity1246 (A) receptor agonist) intracerebroventricularly (icv), @entity8772 ( @entity1246 (A) receptor antagonist) intrathecally (intrathecal), or @entity1363 intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% @entity3727 and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with @entity1363 , gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically. RESULTS: The @entity3727 -induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal @entity8772 , and intraperitoneal @entity1363 . @entity1363 inhibited @entity3727 -induced @entity5019 expression (a marker of neuronal activation) in the pontine A7 and spinal cord. CONCLUSIONS: The GABAergic neurons modulate the antinociceptive effect of @entity3727 in opposite directions at supraspinal and spinal levels. The pronociceptive effects of enhancement at the supraspinal GABAergic site predominate in response to systemically administered @entity1363 .

GABAergic interneurons at supraspinal and spinal levels differentially modulate the antinociceptive effect of XXXX in Fischer @entity35 .

@entity6341 :: ('MESH:D009118', 'Chemical') :: ['muscimol'] @entity3727 :: ('CHEBI:17045', 'Chemical') :: ['N(2)O'] @entity1246 :: ('MESH:D005680', 'Chemical') :: ['gamma-aminobutyric acid', 'GABA'] @entity5019 :: ('314322(Tax:10116)', 'Gene') :: ['c-Fos'] @entity3810 :: ('MESH:D009609', 'Chemical') :: ['nitrous oxide'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['norepinephrine'] @entity1363 :: ('MESH:D008874', 'Chemical') :: ['Midazolam', 'midazolam'] @entity8772 :: ('MESH:C049853', 'Chemical') :: ['gabazine']
@entity3810 :: (MESH:D009609,Chemical) :: ['nitrous oxide']
