| Project/Area Number |
15591617
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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, Graduate School of Medicine, Assistant Professor, 大学院・医学研究院, 講師 (10206253)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | cancer pain / neuropathic pain / spontaneous pain / pain model / dynorphin A / c-fos / astrocyte / dorsal horn / dorsal horn / ostrocyte |
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| Research Abstract |
We investigated some neurochemical changes that take place in the spinal cord dorsal horn in a mouse model of neuropathic cancer pain. The model was produced by inoculation of Meth-A sarcoma cells to the vicinity of the sciatic nerve, which resulted in growth of a tumor mass embedding the nerve. Hind paw-lifting, a behavioral sign of spontaneous pain, was at maximum on day 18,but decreased thereafter. The decrease was likely caused by progression of motor paralysis. On day 18,thermal and mechanical pain thresholds of the affected paw were significantly increased. Histologically, the sciatic nerve presented damages to both unmyelinated and myelinated fibers on day 18,which were more pronounced on day 25. In the spinal cord, c-Fos-positive cells were significantly increased in the superficial and deep layers on day 18. The number of c-Fos-positive cells in the superficial layer correlated with the duration of paw-lifting. The increase in c-Fos-positive cells was still present on day 25 despite decreased paw-lifting. Substance P and calcitonin gene-related peptide were up-regulated on day 18 but down-regulated on day 25. A marked up-regulation of dynorphin A was present on day 18 and persisted through day 25.
Our model caused progressive damage to the sciatic nerve and presented spontaneous pain-behavior while the paw became hyposensitive to mechanical and thermal stimuli. Since the up-regulation of dynorphin A in the dorsal horn persisted and paralleled the increase in c-Fos-positive cells, the release of dynorphin A may be associated with spontaneous pain in our model.
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