| Project/Area Number |
18613024
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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 |
Pain science
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
DAI Yi Hyogo College of Medicine, Faculty of Medicine, Assistant Professor (20330441)
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| Co-Investigator(Kenkyū-buntansha) |
NOGUCHI Koichi Hyogo College of Medicine, Faculty of Medicine, Professor (10212127)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,080,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | TRPA1 / PAR-2 / PIP2 / PLC / DRG / inflammation / pain / patch clamp / ion channel / neuron |
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| Research Abstract |
Proinflammatory agents trypsin and mast cell tryptase cleave and activate PAR2, which is expressed on sensory nerves to cause neurogenic inflammation. Transient receptor potential channels V1 (TRPV1) and Al (TRPA1) are excitatory ion channel on primary sensory nerves of pain pathway. Here, we show that a functional interaction of PAR2 with TRPV1 or TRPA1 in primary sensory neurons could contribute to the sensation of inflammatory pain.
Frequent colocalization of the TRP channels with PAR2 was found in rat dorsal root ganglion (DRG) neurons.
PAR2 activation could increase both the TRPV1 and TRPA1 currents evoked by its agonists in HEK293 cells transfected with the TRP channels, as well as DRG neurons. However, the cellular mechanism of these potentiation showed Application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP2) suppressed potentiation of TRPA1. Decrease of plasma membrane PIP2 levels through antibody sequestration or PLC-mediated hydrolysis mimicked the potentiating effects of PAR2 activation at the cellular level. Thus, the increased TRPA1 sensitivity may have been due to activation of PLC, which releases the inhibition of TRPA1 from plasma membrane PIP2. These results identify for the first time to our knowledge a sensitization mechanism of TRPA1 and a novel mechanism through which trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation.
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