Jinsil Seong, Presenter: Nothing to Disclose

Hee Chul Park MD, Abstract Co-Author: Nothing to Disclose

Jung Hee An, Abstract Co-Author: Nothing to Disclose

Jiyoung Kim, Abstract Co-Author: Nothing to Disclose

Unjung Kim, Abstract Co-Author: Nothing to Disclose

Baewham Lee, Abstract Co-Author: Nothing to Disclose

Purpose/Objective: Radiotherapy is an effective modality in relief of bone pain from cancer invasion. While it has been widely used in pain palliation, the exact mechanism is not clear yet. We questioned why pain relief occurrs earlier than radiation-induced tumor control. This study was to explore the mechanism in an animal model system. Materials/Methods: Hind paw model of cancer pain was developed by transplanting murine hepatocarcinoma, HCa-1, into the periosteal membrane of foot dorsum in C3H/HeJ mice. Bone invasion from HCa-1 was histopathologically confirmed in sequential tumor region sampling. By assessing pain-associated behaviour, development of pain in tumor-growing mice and any change of pain level by radiating tumor were objectively examined. Expression of known pain-related molecules involving calcitonin gene-related peptide (CGRP), substance P and c-fos was examined by immuno-histochemical staining. Finally, the differential expression of pain-related signals in the spinal cord was analyzed for 3 experimental groups; control, tumor without radiation, and tumor with radiation by proteomic analysis using high-resolution 2-dimensional gel electrophoresis (2-DE) and mass spectrometry. Results: In the histopathological examinations, bone invasion from HCa-1 was seen from day 7 and evident at day 14 after transplantation. Measurable pain-associated behaviors were developed from day 7. After radiation (25 Gy) on tumors, objective level of pain decreased with a higher threshold to mechanical stimulation than in control. After irradiating tumor, significant decrease in the expression of CGRP was shown in immunohistolochemical staining of the spinal cord, while neither substance P nor c-fos showed any alteration. In 2-DE of spinal cord, 110 spots were identified. There were 4 proteins that increased in tumor without radiation group comparing to control, but decreased in tumor with radiation group. These involved secretagogin, syntenin, cell growth regulatory with ring finger domain, and Ca2+/calmodulin-dependent protein kinase type 1 (CaM kinase 1), which have been known to be involved in the Ca2+-signaling cascade or in controlling vesicular trafficking. Conclusions: We developed a novel 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. Underlying mechanism seems to be related with Ca2+-signaling cascade or controlling vesicular trafficking.

Seong, J, Park, H, An, J, Kim, J, Kim, U, Lee, B, Radiation-induced Relief of Bone Pain from Cancer Invasion: Proteomic Analysis of Pain Signals in an Animal Model.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4417824.html