In vivo patch-clamp analysis of dopaminergic antinociceptive actions on substantia gelatinosa neurons in the spinal cord.
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 (V(H)=-70mV), 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, Ba(2+). 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.
Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama 641-810, Japan Pain Research Center, Kansai University of Health Sciences, Kumatori, Osaka 590-0482, Japan Department of Physiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
Wataru
W
Taniguchi
Terumasa
T
Nakatsuka
Nobuyuki
N
Miyazaki
Hiroshi
H
Yamada
Daisuke
D
Takeda
Tsugumi
T
Fujita
Eiichi
E
Kumamoto
Munehito
M
Yoshida
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010812:Physical Stimulation / Q000009:adverse effects; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013116:Spinal Cord / Q000033:anatomy & histology*; D013376:Substantia Gelatinosa / Q000166:cytology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D017609:Barium Compounds; D002712:Chlorides; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D026941:Sodium Channel Blockers; D013873:Thionucleotides; C024986:barium chloride; D006153:Guanosine Diphosphate; D019257:Quinpirole; D013779:Tetrodotoxin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C023427:guanosine 5'-O-(2-thiodiphosphate); D004298:Dopamine