VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA

Tang, Y.; Peng, Z.; Tao, S.; Sun, J.; Wang, W.; Guo, X.; Liu, G.; Luo, X.; Chen, Y.; Shen, Y.; Ma, H.; Xu, P.; Li, Q. H.; Zhang, H.; Feng, Z.

doi:10.1101/655498

bioRxiv · 10.1101/655498

VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA

Tang, Y.·Peng, Z.·Tao, S.·Sun, J.·Wang, W.·Guo, X.·Liu, G.·Luo, X.·Chen, Y.·Shen, Y.·Ma, H.·Xu, P.·Li, Q. H.·Zhang, H.·Feng, Z.

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Abstract

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating the heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in mediating release of glutamate, contributed to the inflammatory heat. It remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in Inflammatory pain mediated by Cdk5 and the heat hyperalgesia induced by complete Freunds adjuvant (CFA) can be reversed by roscovitine, a selective inhibitor for Cdk5 through inhibition of VGLUT2 expression. Immunohistochemistry results suggest that when compared with rats in a control group, rats in an experimental group showed significant coexpression of Cdk5/VGLUT2 in small and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA. Moreover, our study revealed that the expression of VGLUT2 protein in DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection. Additionally, p25 but not p35, a activator of Cdk5, protein was significantly increased and reduced by roscovitine. The increased expressions of VGLUT2 protein was significantly reduced by roscovitine as well. Our study showed that VGLUT2/Cdk5 signaling pathway contributed to the inflammatory pain medicated by Cdk5/p25.

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Tang, Y., Peng, Z., Tao, S., Sun, J., Wang, W., Guo, X., Liu, G., Luo, X., Chen, Y., Shen, Y., Ma, H., Xu, P., Li, Q. H., Zhang, H., Feng, Z.. 2019-05-30. VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA. https://doi.org/10.1101/655498

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