@article{02f1c5fe36ce4980be9f23cfee6d528a,
title = "Adjacent intact nociceptive neurons drive the acute outburst of pain following peripheral axotomy",
abstract = "Injury of peripheral nerves may quickly induce severe pain, but the mechanism remains obscure. We observed a rapid onset of spontaneous pain and evoked pain hypersensitivity after acute transection of the L5 spinal nerve (SNT) in awake rats. The outburst of pain was associated with a rapid development of spontaneous activities and hyperexcitability of nociceptive neurons in the adjacent uninjured L4 dorsal root ganglion (DRG), as revealed by both in vivo electrophysiological recording and high-throughput calcium imaging in vivo. Transection of the L4 dorsal root or intrathecal infusion of aminobutyrate aminotransferase inhibitor attenuated the spontaneous activity, suggesting that retrograde signals from the spinal cord may contribute to the sensitization of L4 DRG neurons after L5 SNT. Electrical stimulation of low-threshold afferents proximal to the axotomized L5 spinal nerve attenuated the spontaneous activities in L4 DRG and pain behavior. These findings suggest that peripheral axotomy may quickly induce hyperexcitability of uninjured nociceptors in the adjacent DRG that drives an outburst of pain.",
author = "Zhiyong Chen and Tao Wang and Yehong Fang and Dan Luo and Michael Anderson and Qian Huang and Shaoqiu He and Xiaodan Song and Huan Cui and Xinzhong Dong and Yikuan Xie and Yun Guan and Chao Ma",
note = "Funding Information: The authors thank Claire F. Levine, MS (scientific editor, Department of Anesthesiology/CCM, Johns Hopkins University) for editing the manuscript, and Drs. James Campbell and Srinivasa N Raja for helpful advice and comments. Animal behavioral studies and electrophysiology studies were conducted at the Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Peking Union Medical College, China, and were supported by grants from the National Natural Science Foundation of China (NSFC #81271239, #81771205, #91632113), the Natural Science Foundation and Major Basic Research Program of Shanghai (16JC1420500, 16JC1420502), and the CAMS Innovation Fund for Medical Sciences (CIFMS #2017-I2M-3-008). The GCaMP imaging study in anesthetized mice was conducted at the Johns Hopkins University, Baltimore, MD, USA. This work was also facilitated by the Pain Research Core funded by the Blaustein Fund and the Neurosurgery Pain Research Institute at the Johns Hopkins University (Director, Y.G.). Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41598-019-44172-9",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}