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

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 [center dot O-2] and hydroxyl radicals [center dot OH]-in neuropathic mechanical hyperalgesia and cell type-specific spinal synaptic plasticity. The [center dot O-2] donor induced stronger mechanical hyperalgesia than the [center dot OH] donor in naive mice. The [center dot O-2] scavenger showed greater antihyperalgesic effect than [center dot OH] scavengers in the spinal nerve ligation (SNL) mouse model of neuropathic pain. In addition, the [center dot O-2] donor induced both STTn-LTP and GABAn-LTD, but the [center dot OH] donor induced only GABAn-LTD. On the other hand, the [center dot O-2] scavenger inhibited STTn-LTP and GABAn-LTD induction in naive mice and alleviated SNL-induced potentiation in STTn and depression in GABAn. The [center dot 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 [center dot O-2] mediates both STTn-LTP and GABAn-LTD, whereas [center dot OH] is involved primarily in GABAn-LTD.