adenosine-5--(n-ethylcarboxamide) and nictindole

The effects of locus coeruleus stimulation on nociceptive evoked discharges of thalamic parafascicular (PF) neurons were investigated in lightly urethane-anesthetized rats, aiming to study the mechanisms underlying these effects. Intrathecal (i.t.) administration of aminophylline (an adenosine antagonist), glibenclamide (an ATP-sensitive potassium [K+(ATP)] channels blocker), nicrorandil (Nico; an agonist of K+(ATP) channel and a K+(ATP) channel opener), and 5'-N-ethylcarboxamido-adenosine (NECA; an adenosine agonist) were used. The results showed that (1) locus coeruleus stimulation significantly inhibited the nociceptive evoked discharges of parafascicular neurons, (2) locus coeruleus stimulation-produced antinociception in PF neurons was blocked by both it. glibenclamide and i.t. aminophylline, (3) nociceptive discharges of PF neurons were also suppressed by both i.t. NECA and i.t. nicorandil, and (4) i.t. glibenclamide showed no effect on the suppression of nociceptive discharges induced by NECA, whereas aminophylline blocked the suppression of nociceptive discharges induced by nicorandil. These results suggest that (a) K+(ATP) channels and endogenous adenosine may be involved in the mediation of antinociception induced by norepinephrine, which is released in the dorsal horn by descending fibers originating from the locus coeruleus and (b) the opening of K+(ATP) channels may precede the release of endogenous adenosine in the process of suppressing nociceptive transmission at the spinal level.

Topics: Action Potentials; Adenosine; Adenosine Triphosphate; Adenosine-5'-(N-ethylcarboxamide); Aminophylline; Animals; Drug Interactions; Electric Stimulation; Female; Glyburide; Indoles; Intralaminar Thalamic Nuclei; Locus Coeruleus; Male; Neural Inhibition; Neurons; Nociceptors; Phosphodiesterase Inhibitors; Potassium Channel Blockers; Potassium Channels; Rats; Rats, Wistar