Involvement of reactive oxygen species in long-term potentiation in the spinal cord dorsal horn.
Recent studies suggest that reactive oxygen species (ROS) are functional messenger molecules in central sensitization, an underlying mechanism of persistent pain. Because spinal cord long-term potentiation (LTP) is the electrophysiological basis of central sensitization, this study investigates the effects of the increased or decreased spinal ROS levels on spinal cord LTP. Spinal cord LTP is induced by either brief, high-frequency stimulation (HFS) of a dorsal root at C-fiber intensity or superfusion of a ROS donor, tert-butyl hydroperoxide (t-BOOH), onto rat spinal cord slice preparations. Field excitatory postsynaptic potentials (fEPSPs) evoked by dorsal root stimulations with either Abeta- or C-fiber intensity are recorded from the superficial dorsal horn. HFS significantly increases the slope of both Abeta- and C-fiber evoked fEPSPs, thus suggesting LTP development. The induction, not the maintenance, of HFS-induced LTP is blocked by a N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonopentanoic acid (D-AP5). Both the induction and maintenance of LTP of Abeta-fiber-evoked fEPSPs are inhibited by a ROS scavenger, either N-tert-butyl-alpha-phenylnitrone or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. A ROS donor, t-BOOH-induced LTP is inhibited by N-tert-butyl-alpha-phenylnitrone but not by D-AP5. Furthermore, HFS-induced LTP and t-BOOH-induced LTP occlude each other. The data suggest that elevated ROS is a downstream event of NMDA receptor activation and an essential step for potentiation of synaptic excitability in the spinal dorsal horn.
Lee
Kwan Yeop
KY
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 310 University Blvd., Galveston, TX 77555-1069, USA.
Chung
Kyungsoon
K
Chung
Jin Mo
JM
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005071:Evoked Potentials / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013113:Spin Labels; D013126:Spinal Nerve Roots / Q000502:physiology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D002491:Central Nervous System Agents; D003497:Cyclic N-Oxides; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D015763:2-Amino-5-phosphonovalerate; D020122:tert-Butylhydroperoxide; C001803:tempol