Imaging opiate-analgesia related brain regions in a mice cancer-induced bone pain model

• Main Authors: Wen-Hua Chu, 朱玟樺
• Other Authors: Chen-Tung Yen
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/20843045841178991625

碩士 === 國立臺灣大學 === 生命科學系 === 103 === Cancer-induced bone pain (CIBP) is a common pain in patients with advanced cancer. When cancer metastasizes to the bone, it can cause persistent and unbearable pain which often cause patient’s physical and mental suffering. Although CIBP is one of the most serious clinical problems, the pathophysiological mechanism of CIBP has not been elucidated. Opioid, such as morphine, is commonly used in cancer pain management. The aim of this study is to combine the positron emission tomography-computed tomography (PET/CT) imaging and pain behavior tests to investigate the pain- and morphine analgesia-related brain regions in the CIBP mice. We injected 4T1 mouse breast cancer cells into left femur bone marrow cavity of the BALB/c mice, using 18F-NaF as tracer to evaluate the development of cancer cells in the bone environment. Mice in sham control group were injected with phosphate buffered saline. Then, we measured pain related behaviors with limb use observation, von Frey filaments test and acetone stimulus on the day before surgery, Day 7, Day 10 and Day 14 after the surgery to confirm pain development. Morphine doses (10, 15, 30 mg/kg, i.p.) were administered on Day 16 after the surgery. In addition, we investigated spontaneous pain and morphine-analgesic effect on CIBP mice brain by 18F-fluorodeoxyglucose (FDG) PET/CT. In the PET imaging study, each mouse was scanned 3 times: before bone surgery, Day 14, after the surgery, and Day 16, 30 min after the 15 mg/kg morphine treatment. Our results showed that the CIBP mice showed significant spontaneous pain, mechanical allodynia and cold allodynia on 14 days after the 4T1 cancer cells injection. Morphine dose 15 mg/kg was sufficient to relieve spontaneous pain, mechanical and cold allodynia of the CIBP mice between 30 to 60 minutes post-treatment. In PET study, brain glucose metabolic activity of sensory and motor cortex in mice increased during movement, and the results were reversed during sleeping. In order to prevent these results interfering the analysis of CIBP-related brain regions, we removed the activity parameters, and the results showed that in the CIBP condition, glucose metabolic activity were significant increased in bilateral insular cortex and bilateral S2. Morphine analgesia effect may be produced by the observed suppressing contralateral insular cortex and contralateral S2 brain regions, as well as activation of the habenula and PAG. Our data suggest that contralateral insular cortex and contralateral S2 may play an important role in the CIBP.