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Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain

 Alice Bittar  ;  Jaebeom Jun  ;  Jun-Ho La  ;  Jigong Wang  ;  Joong Woo Leem  ;  Jin Mo Chung 
 PAIN, Vol.158(11) : 2137-2146, 2017 
Journal Title
Issue Date
Afferent Pathways/physiopathology ; Animals ; Cyclic N-Oxides/pharmacology ; Disease Models, Animal ; Free Radical Scavengers/therapeutic use ; GABA Agents/pharmacology ; GABAergic Neurons/drug effects ; GABAergic Neurons/physiology* ; Glutamate Decarboxylase/genetics ; Glutamate Decarboxylase/metabolism ; Hydroxyl Radical/metabolism* ; Hyperalgesia/pathology ; Hyperalgesia/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuralgia/drug therapy ; Neuralgia/pathology* ; Neuronal Plasticity/drug effects ; Neuronal Plasticity/physiology* ; Reactive Oxygen Species/metabolism* ; Spin Labels ; Spinal Nerves/injuries ; Spinal Nerves/pathology ; Superoxides/metabolism* ; Synaptic Potentials/drug effects ; Synaptic Potentials/physiology ; Thiourea/analogs & derivatives ; Thiourea/pharmacology
Spinal synaptic plasticity is believed to drive central sensitization that underlies the persistent nature of neuropathic pain. Our recent data showed that synaptic plasticity in the dorsal horn is cell type specific: intense afferent stimulation produced long-term potentiation (LTP) in excitatory spinothalamic tract neurons (STTn), whereas it produced long-term depression (LTD) in inhibitory GABAergic interneurons (GABAn). In addition, reactive oxygen species (ROS) were shown to be involved in LTP in STTn (STTn-LTP) and in LTD in GABAn (GABAn-LTD). This study examined the roles of 2 biologically important ROS--superoxide [·O2] and hydroxyl radicals [·OH]--in neuropathic mechanical hyperalgesia and cell type-specific spinal synaptic plasticity. The [·O2] donor induced stronger mechanical hyperalgesia than the [·OH] donor in naive mice. The [·O2] scavenger showed greater antihyperalgesic effect than [·OH] scavengers in the spinal nerve ligation (SNL) mouse model of neuropathic pain. In addition, the [·O2] donor induced both STTn-LTP and GABAn-LTD, but the [·OH] donor induced only GABAn-LTD. On the other hand, the [·O2] scavenger inhibited STTn-LTP and GABAn-LTD induction in naive mice and alleviated SNL-induced potentiation in STTn and depression in GABAn. The [·OH] scavenger, however, inhibited depression in GABAn but did not interfere with potentiation in STTn. These results indicate that mechanical hyperalgesia in SNL mice is the result of the combination of STTn-LTP and GABAn-LTD. Behavioral outcomes compliment electrophysiological results which suggest that [·O2] mediates both STTn-LTP and GABAn-LTD, whereas [·OH] is involved primarily in GABAn-LTD.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Leem, Joong Woo(임중우) ORCID logo https://orcid.org/0000-0002-1605-2230
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