| Project/Area Number |
11671479
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Chiba University |
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Principal Investigator |
SHIMOYAMA Megumi Chiba University, School of Medicine, Research Associate, 医学部, 助手 (10206253)
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| Co-Investigator(Kenkyū-buntansha) |
AOE Tomohiko Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (90311612)
SHIMOYAMA Naohito National Cancer Center Hospital, Attending, 中央病院, 医長
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | cancer pain / neuropathic pain / animal model / hyperalgesia / allodynia / mouse |
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| Research Abstract |
We developed a mouse model of neuropathic pain by inoculating Meth A sarcoma cells to the immediate proximity of the sciatic nerve in BALB/c mice. The tumor grows predictably with time and gradually compresses the nerve and thereby causes nerve injury. Time courses of thermal hyperalgesia and mechanical sensitivity to von Frey hairs were determined as well as incidence of signs of spontaneous pain. We compared this model with the chronic constriction injury(CCI)model, which is a neuropathic pain model widely utilized in the rat. Furthermore, to determine the difference in nerve injury between the two models, we performed histological examination of the nerve by light and electron microscopy.
Gradual but progressive compression of the sciatic nerve by growth of a tumor resulted in a gradual development of thermal hyperralgesia and mechanical allodynia in the ipsilateral hind paw. However, further compression to the nerve reversed the mechanical hypersensitivity and produced mechanical hyposensitivity. Histologically, gradual compression by the tumor resulted in a progressive damage to the both myelinated and unmyelinated fibers. However, the degree of damage to the myelinated fibers was considerably less compared to that of the CCI mice. In the CCI mice, severe damage to myelinated fibers was observed while unmyelinated fibers were damaged to a lesser degree.
These results suggest that progressive compression of a nerve by a malignant tumor results in nerve damage with a profile considerably different from that of chronic constriction injury produced by loose ligation of the nerve. Our new tumor model may be useful in studies of neuropathic cancer pain due to nerve compression by malignant tumors.
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