TY - JOUR
T1 - Actions of noradrenaline on substantia gelatinosa neurones in the rat spinal cord revealed by in vivo patch recording
AU - Sonohata, Motoki
AU - Furue, Hidemasa
AU - Katafuchi, Toshihiko
AU - Yasaka, Toshiharu
AU - Doi, Atsushi
AU - Kumamoto, Eiichi
AU - Yoshimura, Megumu
PY - 2004/3/1
Y1 - 2004/3/1
N2 - 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 (VH, -70 mV), the application of NA produced an outward current that was blocked by Cs+ and GDP-β-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 (EC50, 20 μM), and the reversal potential was -88 mV. The outward current was mimicked by an α2-adrenoceptor agonist, clonidine, and suppressed by an α2-adrenoceptor antagonist, yohimbine, but not by α1- and β-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 α2-adrenoceptors, thereby producing an antinociceptive effect.
AB - 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 (VH, -70 mV), the application of NA produced an outward current that was blocked by Cs+ and GDP-β-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 (EC50, 20 μM), and the reversal potential was -88 mV. The outward current was mimicked by an α2-adrenoceptor agonist, clonidine, and suppressed by an α2-adrenoceptor antagonist, yohimbine, but not by α1- and β-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 α2-adrenoceptors, thereby producing an antinociceptive effect.
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U2 - 10.1113/jphysiol.2003.054932
DO - 10.1113/jphysiol.2003.054932
M3 - Article
C2 - 14673188
AN - SCOPUS:1642285345
VL - 555
SP - 515
EP - 526
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 2
ER -