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Papers of the Week


Papers: 23 Nov 2019 - 29 Nov 2019


Animal Studies


2019 Nov 20


Pain

NADPH oxidase 2 derived ROS contributes to LTP of C-fiber evoked field potentials in spinal dorsal horn and persistent mirror-image pain following high frequency stimulus of the sciatic nerve.

Abstract

High frequency stimulation (HFS) of the sciatic nerve has been reported to produce long term potentiation (LTP) and long-lasting pain hypersensitivity in rats. However, the central underlying mechanism remains unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) belongs to a group of electron-transporting transmembrane enzymes that produce reactive oxygen species (ROS). Here we found that NOX2 was upregulated in the lumbar spinal dorsal horn after HFS of the left sciatic nerve, which induced bilateral pain and spinal LTP in both male and female rats. Blocking NOX2 with blocking peptide or shRNA prevented the development of bilateral mechanical allodynia, the induction of spinal LTP, and the phosphorylation of N-methyl-d-aspartate (NMDA) receptor 2B (GluN2B) and nuclear factor kappaB (NF-κB) p65 following HFS. Moreover, NOX2 shRNA reduced the frequency and amplitude of both spontaneous excitatory post synaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs) in laminar II neurons. Furthermore, 8-hydroxyguanine (8-OHG), an oxidative stress marker, was increased in the spinal dorsal horn. Spinal application of ROS scavenger, Phenyl-N-tert-butylnitrone (PBN), depressed the already established spinal LTP. Spinal application of H2O2, one ROS, induced LTP and bilateral mechanical allodynia, increased the frequency and amplitude of sEPSCs in laminar II neurons, and phosphorylated GluN2B and p65 in the dorsal horn. The present study provided electrophysiological and behavioral evidence that NOX2- derived ROS in the spinal cord contributed to persistent mirror-image pain by enhancing the synaptic transmission, which was mediated by increasing presynaptic glutamate release and activation of NMDAR and NF-κB in the spinal dorsal horn.