title: Actions of noradrenaline on substantia gelatinosa neurones in the rat spinal cord revealed by in vivo patch recording.
abstract: To elucidate the mechanisms of antinociception mediated by the descending noradrenergic pathway in the spinal cord, the effects of noradrenaline (NA) on noxious synaptic responses of substantia gelatinosa (SG) neurones, and postsynaptic actions of NA were investigated in rats using an in vivo whole-cell patch-clamp technique. Under urethane anaesthesia, the rat was fixed in a stereotaxic apparatus after the lumbar spinal cord was exposed. In the current-clamp mode, pinch stimuli applied to the ipsilateral hindlimb elicited a barrage of EPSPs, some of which initiated an action potential. Perfusion with NA onto the surface of the spinal cord hyperpolarized the membrane (5.0-9.5 mV) and suppressed the action potentials. In the voltage-clamp mode (V(H), -70 mV), the application of NA produced an outward current that was blocked by Cs(+) and GDP-beta-S added to the pipette solution and reduced the amplitude of EPSCs evoked by noxious stimuli. Under the blockade of postsynaptic actions of NA, a reduction of the evoked and spontaneous EPSCs of SG neurones was still observed, thus suggesting both pre- and postsynaptic actions of NA. The NA-induced outward currents showed a clear dose dependency (EC(50), 20 microM), and the reversal potential was -88 mV. The outward current was mimicked by an alpha(2)-adrenoceptor agonist, clonidine, and suppressed by an alpha(2)-adrenoceptor antagonist, yohimbine, but not by alpha(1)- and beta-antagonists. These findings suggest that NA acts on presynaptic sites to reduce noxious stimuli-induced EPSCs, and on postsynaptic SG neurones to induce an outward current by G-protein-mediated activation of K(+) channels through alpha(2)-adrenoceptors, thereby producing an antinociceptive effect.
authors.affiliation: Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Sonohata
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Furue
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Katafuchi
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yasaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Doi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
authors.forename: Megumu
authors.initials: M
authors.lastname: Yoshimura
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002586:Cesium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*; D013376:Substantia Gelatinosa / Q000166:cytology / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D002586:Cesium; C023427:guanosine 5'-O-(2-thiodiphosphate); D009638:Norepinephrine