title: Radiation-induced alteration of pain-related signals in an animal model with bone invasion from cancer.
abstract: Although radiotherapy is highly effective in relieving bone pain from cancer invasion, the mechanism of pain relief remains unclear. To explore the mechanism of radiotherapy-induced analgesia, we have developed an animal model of bone pain resulting from cancer invasion. Using this animal model system, radiation-induced pain response and pain-related signals in the spinal cord were analyzed. The hind paw model of bone pain from cancer invasion was developed by injecting transplantable hepatocellular carcinoma, HCa-1, into the periosteal membrane of the foot dorsum in C3H/HeJ mice. Bony invasion from HCa-1 cells was confirmed by histopathological examinations. We also measured the development of pain-associated behaviors. In this model, changes in the objective level of pain response after irradiation of the tumor were analyzed. Expression of pain-related host signals in the spinal cord, such as calcitonin gene-related peptide (CGRP), substance P, and c-fos, was investigated with immunohistochemical staining. In the histopathological examinations, bone invasion from HCa-1 cells was seen from day 7 and was evident at day 14 after injection. Measurable pain-associated behaviors were developed from day 7. In this model, mice treated with radiotherapy showed decreased objective levels of pain with a higher threshold to graded mechanical stimulation than did control mice from day 3 after irradiation. After irradiation of tumors, significant decreases in the expression of CGRP were shown in the spinal cord, whereas neither substance P nor c-fos showed any alteration. We developed a novel hind paw model of bone pain from cancer invasion that was confirmed by histopathological examination and measurable pain-associated behaviors. Radiotherapy decreased the objective level of pain and the underlying mechanism involved in the alteration of pain-related host signal, CGRP, in the spinal cord.
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, CPO Box 8044, Seoul, Republic of Korea. jsseong@yumc.yonsei.ac.kr
authors.forename: Jinsil
authors.initials: J
authors.lastname: Seong
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Park
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Un Jung
authors.initials: UJ
authors.lastname: Kim
authors.forename: Bae Whan
authors.initials: BW
authors.lastname: Lee
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications / Q000532:radiotherapy* / Q000556:secondary*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D015398:Signal Transduction / Q000528:radiation effects*; D013116:Spinal Cord / Q000503:physiopathology; D013373:Substance P / Q000378:metabolism
chemical_list: D013373:Substance P; D015740:Calcitonin Gene-Related Peptide