title: Study of breakthrough cancer pain in an animal model induced by endothelin-1.
abstract: 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.
authors.affiliation: Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan Province, China.
authors.forename: Yixun
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gan
authors.affiliation: Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan Province, China.
authors.forename: Raoxiang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Medical Experimental Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Huang
authors.affiliation: Medical Experimental Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan Province, China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pathology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Orthopaedics, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zang
authors.affiliation: Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: huangdong6619@vip.163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sichuan Medical University, Luzhou, Sichuan Province, China; Visiting Professor, Central South University, Changsha, Hunan Province, China. Electronic address: shousongc@gmail.com.
authors.forename: Shousong
authors.initials: S
authors.lastname: Cao
mesh_terms: D000200:Action Potentials; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D059390:Breakthrough Pain / Q000139:chemically induced / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1; D006614:Hindlimb / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000503:physiopathology*; D009412:Nerve Fibers / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D012584:Sciatic Nerve / Q000503:physiopathology
chemical_list: D000701:Analgesics, Opioid; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D009020:Morphine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
keywords: Animal model; BQ-123; Breakthrough cancer pain; Cancer; Endothelin-1