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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.
J Mol Neurosci. 2015 Mar; 55(3):706-14.JM

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.

Authors+Show Affiliations

Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing, 100053, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25344153

Citation

Bao, Yanju, et al. "Increased Expression of Protease-activated Receptor 2 and 4 Within Dorsal Root Ganglia in a Rat Model of Bone Cancer Pain." Journal of Molecular Neuroscience : MN, vol. 55, no. 3, 2015, pp. 706-14.
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. 2015;55(3):706-14.
Bao, Y., Hou, W., Yang, L., Liu, R., Gao, Y., Kong, X., Shi, Z., Li, W., Zheng, H., Jiang, S., & Hua, B. (2015). Increased expression of protease-activated receptor 2 and 4 within dorsal root ganglia in a rat model of bone cancer pain. Journal of Molecular Neuroscience : MN, 55(3), 706-14. https://doi.org/10.1007/s12031-014-0409-1
Bao Y, 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. 2015;55(3):706-14. PubMed PMID: 25344153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased expression of protease-activated receptor 2 and 4 within dorsal root ganglia in a rat model of bone cancer pain. AU - Bao,Yanju, AU - Hou,Wei, AU - Yang,Liping, AU - Liu,Rui, AU - Gao,Yebo, AU - Kong,Xiangying, AU - Shi,Zhan, AU - Li,Weidong, AU - Zheng,Honggang, AU - Jiang,Shulong, AU - Hua,Baojin, Y1 - 2014/10/26/ PY - 2013/12/19/received PY - 2014/08/20/accepted PY - 2014/10/26/entrez PY - 2014/10/26/pubmed PY - 2015/10/16/medline SP - 706 EP - 14 JF - Journal of molecular neuroscience : MN JO - J Mol Neurosci VL - 55 IS - 3 N2 - 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. SN - 1559-1166 UR - https://www.unboundmedicine.com/medline/citation/25344153/Increased_expression_of_protease_activated_receptor_2_and_4_within_dorsal_root_ganglia_in_a_rat_model_of_bone_cancer_pain_ L2 - https://dx.doi.org/10.1007/s12031-014-0409-1 DB - PRIME DP - Unbound Medicine ER -