The BDNF-TrkB Signaling Pathway Is Involved in Heat Hyperalgesia Mediated by Cdk5 in RatsReportar como inadecuado




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Background

Cyclin-dependent kinase 5 Cdk5 has been shown to play an important role in mediating inflammation-induced heat hyperalgesia. However, the underlying mechanism remains unclear. The aim of this study was to determine whether roscovitine, an inhibitor of Cdk5, could reverse the heat hyperalgesia induced by peripheral injection of complete Freund-s adjuvant CFA via the brain-derived neurotrophic factor BDNF-tyrosine kinase B TrkB signaling pathway in the dorsal horn of the spinal cord in rats.

Results

Heat hyperalgesia induced by peripheral injection of CFA was significantly reversed by roscovitine, TrkB-IgG, and the TrkB inhibitor K252a, respectively. Furthermore, BDNF was significantly increased from 0.5 h to 24 h after CFA injection in the spinal cord dorsal horn. Intrathecal adminstration of the Cdk5 inhibitor roscovitine had no obvious effects on BDNF levels. Increased TrkB protein level was significantly reversed by roscovitine between 0.5 h and 6 h after CFA injection. Cdk5 and TrkB co-immunoprecipitation results suggested Cdk5 mediates the heat hyperalgesia induced by CFA injection by binding with TrkB, and the binding between Cdk5 and TrkB was markedly blocked by intrathecal adminstration of roscovitine.

Conclusion

Our data suggested that the BDNF-TrkB signaling pathway was involved in CFA-induced heat hyperalgesia mediated by Cdk5. Roscovitine reversed the heat hyperalgesia induced by peripheral injection of CFA by blocking BDNF-TrkB signaling pathway, suggesting that severing the close crosstalk between Cdk5 and the BDNF-TrkB signaling cascade may present a potential target for anti-inflammatory pain.



Autor: Hong-Hai Zhang, Xiao-Qin Zhang, Qing-Sheng Xue, Yan-Luo, Jin-Lu Huang, Su Zhang, Hai-Jun Shao, Han Lu, Wen-Yuan Wang, Bu-Wei Yu

Fuente: http://plos.srce.hr/



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