2006 Fiscal Year Final Research Report Summary
Mechanisms of bone cancer pain
| Project/Area Number |
16390455
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
NAMIKI Akiyoshi Sapporo Medical University School of Medicine, Department of Anesthesiology, Professor, 医学部, 教授 (00136954)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAMATA Tomoyuki Sapporo Medical University School of Medicine, Department of Anesthesiology, Assistant professor, 医学部, 講師 (80336388)
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| Project Period (FY) |
2004 – 2006
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| Keywords | TRPV1 / mu opioid receptor / bone cancer / cancer pain / immunohistochemistry / mRNA / CGRP / IB4 |
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| Research Abstract |
Although mu opioid receptor (MOR) agonists are used in treating most type of pain, a recent study suggested that the sensitivity of bone cancer pain to morphine was lower than that of inflammatory pain. However, the reasons for this have remained unclear. In this study, MOR expression and the analgesic effects of morphine in a bone cancer model were compared with those in an inflammatory pain model. A bone cancer pain model and an inflammatory pain model were made by injection of sarcoma cells into the intramedullary space of the femur and hindpaw injection of complete Freund's adjuvant (CFA), respectively. In behavioral study, mice with sarcoma injection showed flinching behavior of comparable magnitude induced by CFA-induced inflammation. Both intraperitoneal and intrathecal morphine was less effective on flinching behavior of mice with bone cancer than that of mice with CFA injection. Western blot analysis showed that MOR expression in dorsal root ganglion (DRG) ipsilateral to sarcoma injection was significantly reduced, while that ipsilateral to CFA injection was increased. In mice with sarcoma injection, the percentage of MOR-positive DRG neurons was lower than that in control mice (30.3% vs. 45.2%, respectively). In particular, MOR expression was reduced among CGRP- and TRPV1-positive DRG neurons, which are believed to be nociceptive (from 61.5% to 41.5% and from 72.1% to 48.4%, respectively). These results suggest that down-regulation of MOR in a distinct population of DRG neurons contribute to the relative inefficacy of morphine in treating bone cancer pain.
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