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  • Protease-Activated Receptor 2 Antagonist Potentiates Analgesic Effects of Systemic Morphine in a Rat Model of Bone Cancer Pain

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Protease-Activated Receptor 2 Antagonist Potentiates Analgesic Effects of Systemic Morphine in a Rat Model of Bone Cancer Pain
  1. Yanju Bao, MD*,
  2. Wei Hou, MD*,
  3. Liping Yang, MD†,
  4. Xiangying Kong, MD‡,
  5. Maobo Du, MD‡,
  6. Honggang Zheng, MD*,
  7. Yebo Gao, MD*,§ and
  8. Baojin Hua, MD*
  1. *Departments of Oncology Guang’anmen Hospital, China Academy of Chinese Medical Sciences
  2. †Departments of Nephrology Guang’anmen Hospital, China Academy of Chinese Medical Sciences
  3. ‡Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences
  4. §Beijing University of Chinese Medicine, Beijing, China
  1. Address correspondence to: Baojin Hua, MD, Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing 100053, China (e-mail: huabaojin2008{at}126.com).

Abstract

Background and Objectives Bone cancer pain affects the quality of life of cancer patients. This study was aimed at investigating the analgesic effects of combined therapies with an antagonist of proteinase-activated receptor (PAR) 2 and morphine on pain-related behaviors in a rat model of bone cancer pain.

Methods Female Wistar rats were inoculated intramedullarily with Walker 256 cells into their tibias. The analgesic effects of intraperitoneal treatment with morphine and/or intrathecal with the PAR2 antagonist, FSLLRY-NH2, on bone cancer pain–related behaviors in rats were examined.

Results Treatment with morphine at 3 or 10 mg/kg significantly improved limb-use and weight-bearing scores and reduced the number of spontaneous flinches in rats. Treatment with FSLLRY-NH2 at 10 mmol/L also significantly improved limb use and weight bearing scores, and reduced the number of spontaneous flinches in rats. Combination a sub-analgesic dose of FSLLRY-NH2 (0.1 mmol/L) and morphine further elevated limb-use and weight-bearing scores and reduced the number of flinches compared with the effects of morphine alone in rats.

Conclusions Our data indicate that the combination of morphine and FSLLRY-NH2 has potent analgesic effects on bone cancer pain and our findings may aid in design of new strategies for the treatment of bone cancer pain.

https://doi.org/10.1097/AAP.0000000000000211

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    Footnotes

    • Y.B. and W.H. contributed equally to this study.

    • This study was partially supported by the grants from 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 article.

      The authors declare no conflict of interest.