Study of breakthrough cancer pain in an animal model induced by endothelin-1

• Published in: Neuroscience letters Vol. 617; pp. 108 - 115
• Main Authors: Tang, Yixun, Peng, Hao, Liao, Qian, Gan, Li, Zhang, Raoxiang, Huang, Lihua, Ding, Zhigang, Yang, Hui, Yan, Xuebin, Gu, Yonghong, Zang, Xiaofang, Huang, Dong, Cao, Shousong
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 23-03-2016
• Subjects: Action Potentials; Analgesics, Opioid - pharmacology; Animal model; Animals; BQ-123; Breakthrough cancer pain; Breakthrough Pain - chemically induced; Breakthrough Pain - physiopathology; Cancer; Cell Line, Tumor; Disease Models, Animal; Endothelin A Receptor Antagonists - pharmacology; Endothelin-1; Hindlimb - physiopathology; Male; Mice, Inbred C57BL; Morphine - pharmacology; Motor Activity; Neoplasm Transplantation; Neoplasms - physiopathology; Nerve Fibers - physiology; Peptides, Cyclic - pharmacology; Sciatic Nerve - physiopathology; BTcP; Animal model; LLC; Breakthrough cancer pain; ET-1; Endothelin-1; PID; i.p; BQ-123; BTP; Cancer
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.01.053

•We established an animal model of breakthrough cancer pain for the first time which shows high resemblance compared to the breakthrough cancer pain in human clinically.•The animal model of breakthrough cancer pain was induced by endothelin-1. The selective ETA receptor antagonist BQ-123 could reverse breakthrough pain.•We studied the characteristics of pain behaviors such as hind limb use score and voluntary wheel running with the model.•We also studied the electrophysiology of sciatic nerve fiber in corresponding to the pain behaviors with the model.•The model provides a platform for further study of the pathogenesis of breakthrough cancer pain and related targeted intervention.
Cancer patients with bone metastases often suffer breakthrough pain. However, little progress has been made in the treatment of breakthrough pain and its associated mechanism(s) in the patient with cancer due to lacking of resembling and predictive animal models. We previously have demonstrated that endothelin-1 plays an important role in breakthrough cancer pain. In the present study, we have established an animal model of breakthrough cancer pain induced by endothelin-1. The animal model of breakthrough cancer pain is strictly followed the definition and meets the characteristics of breakthrough pain. The model is reliable, reproducible and easy to be produced. To our knowledge, this is the first report for establishing such an animal model. In addition, we also found that a selective ETA receptor antagonist BQ-123 could reverse endothelin-1 induced breakthrough pain. We further studied the characteristics of pain behaviors such as hind limb use score and voluntary wheel running as well as the electrophysiology of sciatic nerve fibers with the model. The murine model shows high resemblance compared to the breakthrough cancer pain in the patients with cancer clinically. It provides a platform for further study of the pathogenesis of breakthrough cancer pain and targeted intervention.