Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain. Issue 11 (November 2017)

• Record Type: Journal Article
• Authors: Bittar, Alice; Jun, Jaebeom; La, Jun-Ho; Wang, Jigong; Leem, Joong Woo; Chung, Jin Mo
• Is Part Of: Pain. Volume 158:Issue 11(2017)
• Publication Date: 2017-11
• Subjects: Neuropathic pain -- Synaptic plasticity -- Spinal cord -- Spinothalamic tract neurons -- GABAergic interneurons -- Long term potentiation -- Long term depression -- Pain behavior -- Reactive oxygen species -- Spinal nerve ligation; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000001014
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: 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. Abstract : Reactive oxygen species are differentially involved in long-term potentiation and depression in a cell type–specific manner in spinal dorsal horn of neuropathic pain animal model.