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

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.
AuthorsYanju Bao, Gaimei Wang, Yebo Gao, Maobo Du, Liping Yang, Xiangying Kong, Honggang Zheng, Wei Hou, Baojin Hua
JournalOncology reports (Oncol Rep) Vol. 34 Issue 3 Pg. 1449-59 (Sep 2015) ISSN: 1791-2431 [Electronic] Greece
PMID26133236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drugs, Chinese Herbal
  • Neoplasm Proteins
  • Receptor, PAR-2
  • xiaozheng zhitong
Topics
  • Administration, Topical
  • Animals
  • Bone Density (drug effects)
  • Bone Neoplasms (drug therapy, genetics, pathology)
  • Drugs, Chinese Herbal (administration & dosage)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Male
  • Neoplasm Proteins (biosynthesis)
  • Osteosarcoma (drug therapy, genetics, pathology)
  • Pain (chemically induced, drug therapy, genetics, pathology)
  • Rats
  • Receptor, PAR-2 (biosynthesis, genetics)
  • Signal Transduction (drug effects)

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