| Project/Area Number |
24659295
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Pain science
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 神経障害性疼痛 / 転写因子 / スプライシング / 神経因性疼痛 |
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| Research Abstract |
The pathophysiological mechanism for neuropathic pain, one of the most common types of intractable pain, remains largely unknown. Neuropeptide pituitary adenylate-cyclase activating polypeptide (PACAP), which is distributed in the dorsal root ganglia (DRG) and dorsal horn, is required for the development of spinal sensitization and induction of neuropathic pain. Using an L5-sciatic nerve transection mouse model, we found that following nerve injury PACAP mRNA increased in the DRG. REST4, a neuron-specific splicing isoform of REST produced by the neural-specific SR-related protein of 100 kDa (nSR100) and nSR100 itself also increased. This study shows that PACAP expression in the DRG after nerve injury is controlled by REST4, which is produced by nSR100-dependent alternative splicing of the REST gene. We suggest that elucidation of the detailed mechanism of PACAP up-regulation will lead to a viable target for the treatment of neuropathic pain.
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