A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity
DC Field | Value | Language |
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dc.contributor.author | Yoon, Seo-Yeon | - |
dc.contributor.author | Kwon, Soon-Gu | - |
dc.contributor.author | Kim, Yong Ho | - |
dc.contributor.author | Yeo, Ji-Hee | - |
dc.contributor.author | Ko, Hyoung-Gon | - |
dc.contributor.author | Roh, Dae-Hyun | - |
dc.contributor.author | Kaang, Bong-Kiun | - |
dc.contributor.author | Beitz, Alvin J. | - |
dc.contributor.author | Lee, Jang-Hern | - |
dc.contributor.author | Oh, Seog Bae | - |
dc.date.available | 2020-02-27T19:44:56Z | - |
dc.date.created | 2020-02-07 | - |
dc.date.issued | 2017-01-01 | - |
dc.identifier.issn | 1744-8069 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6502 | - |
dc.description.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 provides new clues into the mechanisms underlying pain deficits associated with SIB and deserves further study in patients with ASD. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | SAGE PUBLICATIONS INC | - |
dc.relation.isPartOf | MOLECULAR PAIN | - |
dc.subject | POSTSYNAPTIC DENSITY PROTEINS | - |
dc.subject | AUTISM SPECTRUM DISORDERS | - |
dc.subject | D-ASPARTATE NMDA | - |
dc.subject | MECHANICAL ALLODYNIA | - |
dc.subject | SIGMA-1 RECEPTOR | - |
dc.subject | SIGNALING PATHWAYS | - |
dc.subject | NEUROPATHIC PAIN | - |
dc.subject | NR1 SUBUNIT | - |
dc.subject | MICE | - |
dc.subject | PHOSPHORYLATION | - |
dc.title | A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000399901100001 | - |
dc.identifier.doi | 10.1177/1744806916688902 | - |
dc.identifier.bibliographicCitation | MOLECULAR PAIN, v.13 | - |
dc.identifier.scopusid | 2-s2.0-85014465644 | - |
dc.citation.title | MOLECULAR PAIN | - |
dc.citation.volume | 13 | - |
dc.contributor.affiliatedAuthor | Kim, Yong Ho | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Shank2 | - |
dc.subject.keywordAuthor | N-methyl-D-aspartate receptor | - |
dc.subject.keywordAuthor | pain | - |
dc.subject.keywordAuthor | spinal cord | - |
dc.subject.keywordAuthor | extracellular signal-regulated kinase | - |
dc.subject.keywordPlus | POSTSYNAPTIC DENSITY PROTEINS | - |
dc.subject.keywordPlus | AUTISM SPECTRUM DISORDERS | - |
dc.subject.keywordPlus | D-ASPARTATE NMDA | - |
dc.subject.keywordPlus | MECHANICAL ALLODYNIA | - |
dc.subject.keywordPlus | SIGMA-1 RECEPTOR | - |
dc.subject.keywordPlus | SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | NEUROPATHIC PAIN | - |
dc.subject.keywordPlus | NR1 SUBUNIT | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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