SNAP25/syntaxin4/VAMP2/Munc18-1 complexes in spinal dorsal horn contributed to inflammatory pain

Publication date: Available online 19 January 2020Source: NeuroscienceAuthor(s): Xing-Lian Duan, Zhen Guo, Yong-Tao He, Yin-Xia Li, Yan-Ni Liu, Hu-Hu Bai, Hu-Ling Li, Xiao-Dong Hu, Zhan-Wei SuoAbstractSoluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) have been implicated in the trafficking of postsynaptic glutamate receptors, including N-methyl-D-aspartate (NMDA)-subtype glutamate receptors (NMDARs) that are critical for nociceptive plasticity and behavioral sensitization. However, the components of SNAREs complex involved in spinal nociceptive processing remain largely unknown. Here we found that SNAP25, syntaxin4, VAMP2 and Munc18-1 were localized at postsynaptic sites and formed the complex in the superficial lamina of spinal cord dorsal horn of rats. The complex formation between these SNAREs components were accelerated after intraplantar injection of complete Freund's adjuvant (CFA), pharmacological removal of GABAergic inhibition or activation of NMDAR in intact rats. The increased SNAP25/syntaxin4/VAMP2/Munc18-1 interaction facilitated the surface delivery and synaptic accumulation of NMDAR during inflammatory pain. Disruption of the molecular interaction between SNAP25 with its SNARE partners by using a blocking peptide derived from the C-terminus of SNAP25 effectively repressed the surface and synaptic accumulation of GluN2B-containing NMDARs in CFA-injected rats. This peptide also alleviated inflammatory mechanical allodynia and thermal...

Source: Neuroscience - January 19, 2020 Category: Neuroscience Source Type: research