Abstract
IntroductionSynaptosomal associated proteins of 25 kDa (SNAP-25), as a member of stable soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex, is critical for membrane fusion and required for the release of neurotransmitters. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is implicated in pathologic pain. This study aimed to investigate whether and how SNAP-25 regulated AMPA receptors in neuropathic pain. MethodsMale Sprague–Dawley rats underwent L4 spinal nerve ligation (SNL) or the sham procedure. After assessing mechanical allodynia and thermal sensitivity, the ipsilateral portion of the L4-5 spinal cord was harvested. The expression level of SNAP-25 was analyzed by Western blot analysis and real-time quantitative polymerase chain reaction. SNAP-25 phosphorylation and AMPA receptor membrane trafficking levels were evaluated with Western blot analysis. An association between SNAP-25 and AMPA membrane trafficking was confirmed by SNAP-25 expression or phosphorylation inhibition. ResultsThe SNL procedure induced and maintained mechanical allodynia and thermal hyperalgesia. SNL increased the expression and phosphorylation of SNAP-25 and the membrane trafficking of AMPA receptors in the spinal cord. SNAP-25 expression or phosphorylation inhibition alleviated neuropathic pain and downregulated membrane trafficking of AMPA receptors after SNL. GluA1-containing AMPA receptor inhibition relieved mechanical allodynia and thermal hyperalgesia after SNL. ConclusionsThe upregulation of SNAP-25-dependent membrane trafficking of AMPA receptors via SNAP-25 phosphorylation at Ser187 contributed to SNL-induced neuropathic pain. Thus, the inhibition of SNAP-25 expression or phosphorylation might serve as a treatment for neuropathic pain. However, the mechanism of GluA1-containing AMPA receptor membrane trafficking mediated by SNAP-25 phosphorylation in neuropathic pain deserves further exploration.
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