ATP-sensitive potassium channels and endogenous adenosine are involved in spinal antinociception produced by locus coeruleus stimulation.
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.
Han
Bao-Fen
BF
Department of Neurobiology, Shanxi Medical University, Taiyuan, Shanxi, PR, China.
Zhang
Ce
C
Reyes-Vazquez
Cruz
C
Qiao
Jian-Tian
JT
Dafny
Nachum
N
D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D000241:Adenosine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation / Q000009:adverse effects / Q000379:methods; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020646:Intralaminar Thalamic Nuclei / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008125:Locus Coeruleus / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009619:Nociceptors / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000628:Aminophylline; D019830:Adenosine-5'-(N-ethylcarboxamide); D000255:Adenosine Triphosphate; C002092:nictindole; D000241:Adenosine; D005905:Glyburide