PAR2-mediated upregulation of BDNF contributes to central sensitization in bone cancer pain

Molecular Pain

Baojin Hua³  Yinggang Qin³  Conghuang Li³  Shulong Jiang²  Honggang Zheng³  Weidong Li³  Zhan Shi³  Liping Yang¹  Xiangying Kong⁴  Yebo Gao³  Rui Liu³  Wei Hou³  Yanju Bao³ 

[1] Department of Nephrology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, 100053 Beijing, China;Department of Oncology, Jining First People’s Hospital, Healthy Road 6, 272000 Shandong, China;Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, 100053 Beijing, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Nanxiaojie, Dongzhimen District, 100700 Beijing, China

关键词: Bone cancer pain;    Glutamatergic transmission;    Nuclear factor-κB;    Brain-derived neurotrophic factor;    Proteinase-activated receptor 2;   

Others  :  861590
DOI  :  10.1186/1744-8069-10-28

 received in 2013-12-13, accepted in 2014-04-28,  发布年份 2014

【 摘 要 】

Background

Bone cancer pain is currently a major clinical challenge for the management of cancer patients, and the cellular and molecular mechanisms underlying the spinal sensitization remain unclear. While several studies demonstrated the critical role of proteinase-activated receptor (PAR2) in the pathogenesis of several types of inflammatory or neuropathic pain, the involvement of spinal PAR2 and the pertinent signaling in the central sensitization is not determined yet in the rodent model of bone cancer pain.

Findings

Implantation of tumor cells into the tibias induced significant thermal hyperalgesia and mechanical allodynia, and enhanced glutamatergic strength in the ipsilateral dorsal horn. Significantly increased brain-derived neurotrophic factor (BDNF) expression was detected in the dorsal horn, and blockade of spinal BDNF signaling attenuated the enhancement of glutamatergic strength, thermal hyperalgesia and mechanical allodynia in the rats with bone cancer pain. Significantly increased spinal PAR2 expression was also observed, and inhibition of PAR2 signaling ameliorated BDNF upsurge, enhanced glutamatergic strength, and thermal hyperalgesia and mechanical allodynia. Inhibition of NF-κB pathway, the downstream of PAR2 signaling, also significantly decreased the spinal BDNF expression, glutamatergic strength of dorsal horn neurons, and thermal hyperalgesia and mechanical allodynia.

Conclusion

The present study demonstrated that activation of PAR2 triggered NF-κB signaling and significantly upregulated the BDNF function, which critically contributed to the enhancement of glutamatergic transmission in spinal dorsal horn and thermal and mechanical hypersensitivity in the rats with bone cancer. This indicated that PAR2 - NF-κB signaling might become a novel target for the treatment of pain in patients with bone cancer.

【 授权许可】

   
2014 Bao et al.; licensee BioMed Central Ltd.

【 图 表 】

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