In vivo patch-clamp analysis of dopaminergic antinociceptive actions on substantia gelatinosa neurons in the spinal cord |
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Authors: | Taniguchi Wataru Nakatsuka Terumasa Miyazaki Nobuyuki Yamada Hiroshi Takeda Daisuke Fujita Tsugumi Kumamoto Eiichi Yoshida Munehito |
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Affiliation: | a Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama 641-810, Japan b Pain Research Center, Kansai University of Health Sciences, Kumatori, Osaka 590-0482, Japan c Department of Physiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan |
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Abstract: | To elucidate the mechanisms of antinociception mediated by the dopaminergic descending pathway in the spinal cord, we investigated the actions of dopamine (DA) on substantia gelatinosa (SG) neurons by in vivo whole-cell patch-clamp methods. In the voltage-clamp mode (VH = −70 mV), the application of DA induced outward currents in about 70% of SG neurons tested. DA-induced outward current was observed in the presence of either Na+ channel blocker, tetrodotoxin (TTX) or a non-NMDA receptor antagonist, CNQX, and was inhibited by either GDP-β-S in the pipette solution or by perfusion of a non-selective K+ channel blocker, Ba2+. The DA-induced outward currents were mimicked by a selective D2-like receptor agonist, quinpirole and attenuated by a selective D2-like receptor antagonist, sulpiride, indicating that the DA-induced outward current is mediated by G-protein-activated K+ channels through D2-like receptors. DA significantly suppressed the frequency and amplitude of glutamatergic spontaneous excitatory postsynaptic currents (EPSCs). DA also significantly decreased the frequency of miniature EPSCs in the presence of TTX. These results suggest that DA has both presynaptic and postsynaptic inhibitory actions on synaptic transmission in SG neurons. We showed that DA produced direct inhibitory effects in SG neurons to both noxious and innocuous stimuli to the skin. Furthermore, electrical stimulation of dopaminergic diencephalic spinal neurons (A11), which project to the spinal cord, induced outward current and suppressed the frequency and amplitude of EPSCs. We conclude that the dopaminergic descending pathway has an antinociceptive effect via D2-like receptors on SG neurons in the spinal cord. |
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Keywords: | Dopamine In vivo patch-clamp D2-like receptor Spinal cord A11 Inhibitory descending pathway |
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