Persistent Activity of Metabotropic Glutamate Receptor 5 in the Periaqueductal Gray Constrains Emergence of Chronic Neuropathic Pain

被引：20

作者：

Chung, Geehoon ^{[1
,2
,3
]}

Shim, Hyun Geun ^{[1
,4
,10
]}

Kim, Chae Young ^{[1
,4
]}

Ryu, Hyun-Hee ^{[1
,6
]}

Jang, Dong Cheol ^{[1
,3
,11
]}

Kim, Seung Ha ^{[1
,4
]}

Lee, Jaegeon ^{[1
,4
]}

Kim, Chang-Eop ^{[1
,7
]}

Kim, Yu Kyeong ^{[8
]}

Lee, Yong-Seok ^{[1
,4
,6
]}

Kim, Jun ^{[1
]}

Kim, Sun Kwang ^{[2
]}

Worley, Paul F. ^{[9
]}

Kim, Sang Jeong ^{[1
,3
,4
,5
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Physiol, 103 Daehak Ro, Seoul 03080, South Korea

[2] Kyung Hee Univ, Coll Korean Med, Dept Physiol, 26 Kyungheedae Ro, Seoul 02447, South Korea

[3] Seoul Natl Univ, Dept Brain & Cognit Sci, Coll Nat Sci, 1 Gwanak Ro, Seoul 08826, South Korea

[4] Seoul Natl Univ, Coll Med, Dept Biomed Sci, 103 Daehak Ro, Seoul 03080, South Korea

[5] Seoul Natl Univ, Coll Med, Neurosci Res Inst, 103 Daehak Ro, Seoul 03080, South Korea

[6] Chung Ang Univ, Dept Life Sci, 84 Heukseok Ro, Seoul 06974, South Korea

[7] Gachon Univ, Coll Korean Med, Dept Physiol, 1342 Seongnamdaero, Seongnam 13120, South Korea

[8] Seoul Natl Univ, Boramae Med Ctr, Dept Nucl Med, Boramae Ro 5 Gil, Seoul 07061, South Korea

[9] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21205 USA

[10] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA

[11] Neurorive Inc, Seoul, South Korea

来源：

CURRENT BIOLOGY | 2020年 / 30卷 / 23期

基金：

新加坡国家研究基金会;

关键词：

HOMER; EXCITABILITY; NEURONS; MODULATION; ACTIVATION; GREY; TRANSMISSION; MECHANISMS; ANALGESIA; CHANNELS;

D O I：

10.1016/j.cub.2020.09.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4631 / +

页数：18

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[1] Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer [J].