한빛사 논문
Geehoon Chung1,2,3, Hyun Geun Shim1,4,10, Chae Young Kim1,4, Hyun-Hee Ryu1,6, Dong Cheol Jang1,3,11, Seung Ha Kim1,4, Jaegeon Lee1,4, Chang-Eop Kim1,7, Yu Kyeong Kim8, Yong-Seok Lee1,4,6, Jun Kim1, Sun Kwang Kim2, Paul F. Worley9, Sang Jeong Kim1,3,4,5,12,*
1Department of Physiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
2Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
3Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
4Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
5Neuroscience Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
6Department of Life Science, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea
7Department of Physiology, College of Korean Medicine, Gachon University, 1342 Seongnamdaero, Sujeong-gu, Seongnam 13120, Republic of Korea
8Department of Nuclear Medicine, Seoul National University Boramae Medical Center, Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Republic of Korea
9The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
10Present address: Department of Neurobiology, Stanford University, Stanford, California, USA
11Present address: Neurorive Inc., Seoul, Republic of Korea
12Lead Contact
*Corresponding author
Abstract
Pain sensation is powerfully modulated by signal processing in the brain, and pain becomes chronic with the dysfunction of the pain modulatory system; however, the underlying mechanisms are unclear. We found that the metabotropic glutamate receptor 5 (mGluR5) in the periaqueductal gray (PAG), the key area of endogenous pain modulation, is persistently active in normal conditions to maintain an appropriate sensory perception. In the neuropathic pain condition, Homer1a, an activity-dependent immediate early gene product, disrupted the persistent mGluR5 activity resulting in chronic pain. Remarkably a single-time blockage of the mGluR5 resulted in chronic neuropathic pain-like symptoms even in the absence of nerve injury. The decline of mGluR5 activity induced the pain modulatory dysfunction with a profound reduction of excitability of PAG neurons. These findings uncover the role of the persistent mGluR5 activity in vivo and provide new insight into how pain becomes chronic with the maladaptive coping of the PAG to pain sensation.
Keywords : neuropathic pain, chronic pain, descending pain modulation, periaqueductal gray, metabotropic glutamate receptor 5, persistent activity, homer1a, intrinsic excitability, calcium oscillation
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