A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity.

摘要: Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits pain sensation might be one of the contributing factors underlying development SIBs, mechanisms have yet to addressed. Recently, Shank2 synaptic protein has been considered a key component ASD, and mutations SHANK2 gene induce dysfunction N-methyl-D-aspartate (NMDA) receptors, suggesting link between NMDA receptors ASD. Given that spinal play pivotal role hypersensitivity, we investigated possible nociceptive hypersensitivity by examining changes spontaneous following intrathecal injection S hank2-/- ( knock-out, KO) mice. Results Intrathecal evoked behaviors. These NMDA-induced responses were significantly reduced KO We also observed significant decrease currents dorsal horn Subsequently, examined whether mitogen-activated kinase or AKT signaling is involved this behavior mice because receptor closely related these molecules. Western blotting immunohistochemistry revealed spinally administered increased expression phosphorylated form extracellular signal-regulated (p-ERK) which was However, p38, JNK, not changed administration. The ERK inhibitor, PD98059, decreased dose-dependent manner wild-type Moreover, it found increase p-ERK primarily colocalized with proteins cord horn. Conclusion receptor-mediated pain, may suppress NMDA-ERK transmission. This study provides new clues into associated SIB deserves further patients