@article{4cfe5ee6b21746ffafe6e9a042f39738,
title = "A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain",
abstract = "Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest that microglial TRPV4 channels reside at the center of the neuroimmune axis in the spinal cord, which transforms peripheral nerve injury into central sensitization and neuropathic pain, thereby identifying TRPV4 as a potential new target for the treatment of chronic pain.",
author = "Xueming Hu and Lixia Du and Shenbin Liu and Zhou Lan and Kaikai Zang and Jing Feng and Yonghui Zhao and Xingliang Yang and Zili Xie and Wang, {Peter L.} and {Ver Heul}, {Aaron M.} and Lvyi Chen and Vijay Samineni and Wang, {Yan Qing} and Kory Lavine and Gereau, {Robert W.} and Gregory Wu and Hongzhen Hu",
note = "Funding Information: We thank the Washington University Center for Cellular Imaging (WUCCI) for support of the confocal and 2-photon imaging studies, and the Washington University Animal Behavior Core (ABC) for support of the CatWalk gait analysis. We also thank Makoto Suzuki and Atsuko Mizuno for providing Trpv4–/– mice, Drs. Jack B. Cowland, Bin Gao, and Grace Guo for providing Lcn2flox mice, and Mark Hoon for providing Trpv1Cre mice. This work was supported, in whole or in part, by grants from the NIH (R01AA027065, R01AR077183, R01DK103901 to HH, and R01NS106289 to GFW) and Washington University DDRCC (NIDDK P30 DK052574). Publisher Copyright: {\textcopyright} 2023 American Society for Clinical Investigation. All rights reserved.",
year = "2023",
month = mar,
day = "1",
doi = "10.1172/JCI161507",
language = "English",
volume = "133",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
number = "5",
}