Radiation-induced alteration of pain-related signals in an animal model with bone invasion from cancer.
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.
Seong
Jinsil
J
Department of Radiation Oncology, Yonsei University College of Medicine, CPO Box 8044, Seoul, Republic of Korea. jsseong@yumc.yonsei.ac.kr
Park
Hee Chul
HC
Kim
Jiyoung
J
Kim
Un Jung
UJ
Lee
Bae Whan
BW
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
D013373:Substance P; D015740:Calcitonin Gene-Related Peptide