A critical role of spinal Shank2 proteins in NMDA-induced painhypersensitivity

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473545.do
DOI
10.1177/1744806916688902
Title
A critical role of spinal Shank2 proteins in NMDA-induced painhypersensitivity
Description
The author(s) disclosed receipt of the following financial support forthe research, authorship, and/or publication of this article: Thisresearch was supported by the grants of the Korea Health Technology R&DProject through the Korea Health Industry Development Institute (KHIDI),funded by the Ministry of Health & Welfare, Republic of Korea (No.HI15C3077). This work also was supported by the National ResearchFoundation of Korea (NRF) grants funded by the Korea government (MSIP)(No. 2013R1A6A3A04065858, 2014R1A2A2A01007695, 2015R1D1A1A01059208 and2016M3A9B6021209). H-GK and B-KK are supported by the National HonorScientist program.
abstract
Background: Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD. Given that spinal NMDA receptors play a pivotal role in pain hypersensitivity, we investigated the possible role of Shank2 in nociceptive hypersensitivity by examining changes in spontaneous pain following intrathecal NMDA injection in Shank2-/- ( Shank2 knock-out, KO) mice.
Results: Intrathecal NMDA injection evoked spontaneous nociceptive behaviors. These NMDA-induced nociceptive responses were significantly reduced in Shank2 KO mice. We also observed a significant decrease of NMDA currents in the spinal dorsal horn of Shank2 KO mice. Subsequently, we examined whether mitogen-activated protein kinase or AKT signaling is involved in this reduced pain behavior in Shank2 KO mice because the NMDA receptor is closely related to these signaling molecules. Western blotting and immunohistochemistry revealed that spinally administered NMDA increased the expression of a phosphorylated form of extracellular signal-regulated kinase (p-ERK) which was significantly reduced in Shank2 KO mice. However, p38, JNK, or AKT were not changed by NMDA administration. The ERK inhibitor, PD98059, decreased NMDA-induced spontaneous pain behaviors in a dose-dependent manner in wild-type mice. Moreover, it was found that the NMDA-induced increase in p-ERK was primarily colocalized with Shank2 proteins in the spinal cord dorsal horn.
Conclusion: Shank2 protein is involved in spinal NMDA receptor-mediated pain, and mutations of Shank2 may suppress NMDA-ERK signaling in spinal pain transmission. This study
provenance
Made available in Cube on 2018-09-28T10:22:31Z (GMT). No. of bitstreams: 0
language
English
author
Yoon, Seo-Yeon
Kwon, Soon-Gu
Kim, Yong Ho
Yeo, Ji-Hee
Ko, Hyoung-Gon
Roh, Dae-Hyun
Kaang, Bong-Kiun
Beitz, Alvin J.
Lee, Jang-Hern
Oh, Seog Bae
orcid
Beitz, Alvin/0000-0002-2640-2628
accessioned
2018-09-28T10:22:31Z
available
2018-09-28T10:22:31Z
issued
2017
citation
MOLECULAR PAIN(13)
issn
1744-8069
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473545.do
Funder
보건복지부
Funding Program
질환극복기술개발
Project ID
1465021751
Jurisdiction
Rep.of Korea
Project Name
Targeting Chronic pain by Manipulation of the Brain's Reward-pain system
rights
openAccess
subject
Shank2
N-methyl-D-aspartate receptor
pain
spinal cord
extracellularsignal-regulated kinase
type
article


Files in This Item

There are no attached files.