Int J Oral Biol.  2012 Mar;37(1):17-23.

Effects of Mitochondrial Reactive Oxygen Species on Neuronal Excitability in Rat Spinal Substantia Gelatinosa Neurons

• Lee HI
• Park AR
• Chun SW

Abstract

Recent studies indicate that reactive oxygen species (ROS) are critically involved in persistent pain primarily through spinal mechanisms, and that mitochondria are the main source of ROS in the spinal dorsal horn. To investigate whether mitochondrial ROS can induce changes in membrane excitability on spinal substantia gelatonosa (SG) neurons, we examined the effects of mitochondrial electron transport complex (ETC) substrates and inhibitors on the membrane potential of SG neurons in spinal slices. Application of ETC inhibitors, rotenone or antimycin A, resulted in a slowly developing and slight membrane depolarization in SG neurons. Also, application of both malate, a complex I substrate, and succinate, a complex II substrate, caused reversible membrane depolarization and enhanced firing activity. Changes in membrane potential after malate exposure were more prominent than succinate exposure. When slices were pretreated with ROS scavengers such as phenyl-N-tert-buthylnitrone (PBN), catalase and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), malate-induced depolarization was significantly decreased. Intracellular calcium above 100 microM increased malateinduced depolarization, witch was suppressed by cyclosporin A, a mitochondrial permeability transition (MPT) inhibitor. These results suggest that enhanced production of spinal mitochondrial ROS can induce nociception through central sensitization.

Keyword

electron transport complex; malate; succinate; membrane excitability

MeSH Terms

Animals
Antimycin A
Calcium
Catalase
Central Nervous System Sensitization
Cyclosporine
Electron Transport
Fires
Horns
Malates
Membrane Potentials
Membranes
Mitochondria
Neurons
Nociception
Permeability
Rats
Reactive Oxygen Species
Rotenone
Substantia Gelatinosa
Succinic Acid
Antimycin A
Calcium
Catalase
Cyclosporine
Malates
Reactive Oxygen Species
Rotenone
Succinic Acid