title: ATP-sensitive potassium channels and endogenous adenosine are involved in spinal antinociception produced by locus coeruleus stimulation.
abstract: It has been known that locus coeruleus (LC) stimulation suppresses nociceptive discharges of the thalamic parafascicular (PF) neurons through the spinally descending adrenergic terminals which inhibit the transmission of nociceptive signals in the spinal dorsal horn. This experimental model was used in the present study to analyze the detailed processes that happened in the dorsal horn following norepinephrine release by preemptive intrathecal (i.t.) administration of related drugs in lightly urethane-anesthetized rats. The results showed that: (1) LC stimulation significantly inhibited the noxiously-evoked discharges of PF neurons; (2) the LC stimulation-produced antinociception in PF neurons could be blocked either by i.t. glibenclamide, an ATP-sensitive potassium (K(+)(ATP)) channel blocker, or by i.t. aminophylline, an adenosine receptor antagonist; (3) nociceptive discharges of PF neurons were also suppressed both by i.t. 5  -N-ethylcarboxamido-adenosine (NECA, an adenosine receptor agonist) and by i.t. nicorandil (a K(+)(ATP) channel opener); and (4) i.t. aminophylline blocked the suppression of PF nociceptive discharges induced by i.t. nicorandil, while i.t. glibenclamide showed no effect on the suppression of nociceptive discharges induced by i.t. NECA. These results suggest that: (1) K(+)(ATP) channels and endogenous adenosine may be involved in the mediation of spinal antinociception induced by descending adrenergic fibers originating from the LC; and (2) the opening of K(+)(ATP) channels precedes the release of adenosine in the cascade of mediation.
authors.affiliation: Department of Neurobiology, Shanxi Medical University, Taiyuan 030001.
authors.forename: Bao-Fen
authors.initials: BF
authors.lastname: Han
authors.forename: Ce
authors.initials: C
authors.lastname: Zhang
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
authors.forename: Jian-Tian
authors.initials: JT
authors.lastname: Qiao
mesh_terms: D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D007278:Injections, Spinal; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D010146:Pain / Q000503:physiopathology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015221:Potassium Channels; D000255:Adenosine Triphosphate; D000241:Adenosine