Nicotinamide adenine dinucleotide phosphate oxidase 2–derived reactive oxygen species contribute to long-term potentiation of C-fiber-evoked field potentials in spinal dorsal horn and persistent mirror-image pain following high-frequency stimulus of the sciatic nerve

作者：Jing Xu, Xuxia Wei, Feng Gao, Xiongxiong Zhong, Ruixian Guo, Yun Ji, Xin Zhou, Jialiang Chen, Peiwen Yao, Xian‐Guo Liu, Xu‐Hong Wei · 发表于：Pain · 年份：2019 · DOI：10.1097/j.pain.0000000000001761 · 被引用次数：35 · 研究领域：Pain Mechanisms and Treatments、Ion channel regulation and function、Exercise and Physiological Responses

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 kappa-B (NF-κB) p65 after HFS. Moreover, NOX2 shRNA reduced the frequency and amplitude of both spontaneous excitatory postsynaptic currents and miniature excitatory postsynaptic currents 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 spontaneous excitatory postsynaptic currents in laminar II neurons, and phosphorylated GluN2B and p65 in the dorsal horn. This s...