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Spinal Synaptic Scaffolding Protein Homer 1b/c Regulates CREB Phosphorylation and C-Fos Activation Induced by Inflammatory Pain in Rats

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Spinal Synaptic Scaffolding Protein Homer 1b/c Regulates CREB Phosphorylation and C-Fos Activation Induced by Inflammatory Pain in Rats

Yong-Xing Yao et al. Neurosci Lett.

Abstract

Previous studies have shown that spinal Homer 1b/c plays an important role in the maintenance of chronic inflammatory pain induced by complete Freund's adjuvant (CFA). This study investigated the possible mechanism underlying Homer 1b/c mediating CFA-induced inflammatory pain. Chronic inflammation was induced by CFA injection into the left hind ankle of the rat. Homer 1b/c antisense or missense oligonucleotides were administered intrathecally (10μg/10μl) from 5 to 8 days following the onset of inflammation. Immunohistochemistry was conducted to detect the expression of phosphorylated cAMP response element binding protein (pCREB) and Fos protein in the spinal dorsal horn. Intrathecal administration of Homer 1b/c antisense oligonucleotides not only markedly reduced the expression of Homer 1b/c protein, but also attenuated CFA-induced inflammation, spinal CREB phosphorylation, and Fos expression. These results demonstrate for the first time that Homer 1b/c regulates CREB phosphorylation and c-fos activation in the spinal dorsal horn during the maintenance of chronic inflammatory pain, suggesting that Homer 1b/c may be involved in the development of CFA-induced inflammation.

Keywords: CCI; CFA; CREB; Fos; Homer 1b/c; Inflammatory pain; cAMP response element binding protein; chronic constriction injury; complete Freund's adjuvant; mGluRs; metabotropic glutamate receptors.

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