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Increased Expression of Protease-Activated Receptor 2 and 4 Within Dorsal Root Ganglia in a Rat Model of Bone Cancer Pain

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Abstract

In an effort to understand the underlying mechanisms of cancer-induced bone pain, we investigated the presence of two protease-activated receptors, protease-activated receptor 2 (PAR2), and protease-activated receptor 4 (PAR4), in dorsal root ganglia (DRGs) neurons in an animal model of bone cancer pain. Female Wistar rats were randomized into three groups: tumor-bearing animals killed after 14 days (D14) and tumor-bearing animals killed after 21 days (D21) group and a sham operation group. After establishment of the Walker 256 carcinoma bone cancer pain model, behavioral tests were carried out to determine both the spontaneous nocifensive behavior and the paw withdrawal threshold (PWT) of mechanical and thermal hyperalgesia in these rats. Subsequently, real-time RT-PCR, Western bolt, and immunofluorescence were used to determine the messenger RNA (mRNA) and protein expression of PAR2 and PAR4 in the ipsilateral lumbar 4–5 DRG neurons. Rats in the D21 treatment group displayed a significant increase in spontaneous nocifensive behavior scores compared with the sham group as well as a considerably decreased withdrawal threshold in mechanical allodynia and thermal stimulation. Compared to sham group, the relative mRNA and protein expression of PAR2 and PAR4 was significantly upregulated in the D14 group and D21 groups, concurrent with tumor growth and proliferation. In addition, we identified the co-expression of PAR2 and PAR4 in the DRG neurons. The upregulation of mRNA and protein levels as well as the co-localization of PAR2 and PAR4 in DRG neurons suggests their novel involvement in the development and maintenance of bone cancer pain.

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Acknowledgments

The current work was partially supported by the National Natural Science Foundation Project of China (no. 81273718 and no. 81302961). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the paper.

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing, 100053, China

    Yanju Bao, Wei Hou, Rui Liu, Yebo Gao, Zhan Shi, Weidong Li, Honggang Zheng & Baojin Hua

  2. Department of Nephrology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing, 100053, China

    Liping Yang

  3. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Nanxiaojie, Dongzhimen District, Beijing, 100700, China

    Xiangying Kong

  4. Department of oncology, Jining First People’s Hospital, Beijing, Healthy Road 6, Shandong, 272000, China

    Shulong Jiang

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  1. Yanju Bao
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  2. Wei Hou
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  3. Liping Yang
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  4. Rui Liu
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  8. Weidong Li
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  11. Baojin Hua
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Correspondence to Wei Hou or Baojin Hua.

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Bao, Y., Hou, W., Yang, L. et al. Increased Expression of Protease-Activated Receptor 2 and 4 Within Dorsal Root Ganglia in a Rat Model of Bone Cancer Pain. J Mol Neurosci 55, 706–714 (2015). https://doi.org/10.1007/s12031-014-0409-1

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  • DOI: https://doi.org/10.1007/s12031-014-0409-1

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