Topical treatment with Xiaozheng Zhitong Paste alleviates bone cancer pain by inhibiting proteinase-activated receptor 2 signaling pathway

Bao,Yanju; Wang,Gaimei; Gao,Yebo; Du,Maobo; Yang,Liping; Kong,Xiangying; Zheng,Honggang; Hou,Wei; Hua,Baojin

doi:10.3892/or.2015.4073

Topical treatment with Xiaozheng Zhitong Paste alleviates bone cancer pain by inhibiting proteinase-activated receptor 2 signaling pathway

Authors:
- Yanju Bao
- Gaimei Wang
- Yebo Gao
- Maobo Du
- Liping Yang
- Xiangying Kong
- Honggang Zheng
- Wei Hou
- Baojin Hua
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Affiliations: Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Xicheng, Beijing 100053, P.R. China, Department of Gynecology, the Third Hospital of Zhengzhou, Zhengzhou, Henan 450000, P.R. China, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongzhimen, Beijing 100700, P.R. China, Department of Nephrology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Xicheng, Beijing 100053, P.R. China
Published online on: June 24, 2015 https://doi.org/10.3892/or.2015.4073
Pages: 1449-1459

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Abstract

Herbal analgesic Xiaozheng Zhitong Paste (XZP) and related modifications are often used in traditional Chinese medicine to manage cancer pain. However, its underlying mechanism remains unknown. To investigate the effects and mechanism of XZP on bone cancer pain in a rat model of breast cancer-induced bone pain, a bone cancer pain model was established by inoculating Walker 256 cells into Wistar rats. Bone cancer-bearing rats were topically treated with different doses of XZP or injected with 5 mg/kg of osteoprotegerin (OPG) as positive control. Bone destruction, bone mineral content (BMC) and bone mineral density (BMD) were analyzed by radiology. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were examined to determine pain levels. Trypsin, TNF-α and IL-1β serum levels were determined using enzyme-linked immunosorbent assay (ELISA). Central sensitization markers such as c-Fos, GFAP, IBA1 and CGRP, as well as proteinase-activated receptor 2 (PAR2) signaling pathway mediators such as PAR2, PKC-γ, PKA and TRPV1, were determined by quantitative RT-PCR and western blotting assay. XZP treatment significantly mitigated bone cancer-related nociceptive behavior, bone damage, BMC and BMD; and decreased radiological scores in rats. XZP treatment significantly inhibited IBA1, GFAP, c-Fos and CGRP expressions in the spinal cord; and significantly mitigated trypsin, TNF-α and IL-1β serum levels. Furthermore, PAR2, PKC-γ, PKA and TRPV1 relative mRNA levels and protein expression in bone lesions were significantly reduced in rats treated with XZP. XZP significantly alleviates breast cancer-induced bone pain by inhibiting the PAR2 signaling pathway.

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