| Project/Area Number |
17591654
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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 | Hyogo College of Medicine |
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Principal Investigator |
FUKUOKA Tetsuo Hyogo College of Medicine, Faculty of Medicine, Part-time teacher, 医学部, 非常勤講師 (90399147)
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| Co-Investigator(Kenkyū-buntansha) |
OBATA Koichi Hyogo College of Medicine, Faculty of Medicine, Assistat professor, 医学部, 講師 (70368538)
DAI Yi Hyogo College of Medicine, Faculty of Medicine, Assistat professor, 医学部, 講師 (20330441)
NOGUCHI Koichi Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (10212127)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | TRPA1 / TRPM8 / neuropathic pain / DRG / inflammation / CRPS / cold hyperalgesia / TRP / spinal cord / P2Y / Src / MAPK / p75 / Neuropathic / Pain |
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| Research Abstract |
In the passed several years, our knowledge of the molecular mechanisms of temperature transduction of the primary afferent neurons has greatly increased. Multiple temperature-sensitive ion channels have been cloned and classified into subfamilies of transient receptor potential (TRP) ion channels. TRPV1, the first cloned temperature-sensitive TRP, has activation threshold around 42℃, that is a value we feel hot sensation. On the other hand, the recently cloned TRPA1 and TRPM8 are two potential candidates for cold sensors. We have investigated the contribution of TRPA1 and TRPM8 to the pathomechanisms of cold hyperalgesia that is often seen in complex regional pain syndrome (CRPS) patients. TRPA1 is selectively expressed by a subpopulation of TRPV1-positive dorsal root ganglion (DRG) neurons possessing C-fibers in a TrkA-independent manner. On the contrary, TRPM8 is expressed by TRPV1-negative, TrkA-positive DRG neurons with C-or Adelta-fiber. Noxious cold stimulation to the hind paw of the naive rats induced phosphorylation of ERK in the TRPM8-positive neurons and p38 in the TRPA1-positive neurons, indicating that these two ion channels are cold sensors of different subpopulations of DRG neurons in a normal condition.
Both of TRPA1 and TRPM8 mRNAs are down-regulated in the directly axotomized DRG neurons. Peripheral inflammation increased TRPA1, but not TRPM8, mRNA in the suffered DRG neurons. L5 spinal nerve ligation, a neuropathic pain model, also increased TRPA1, but not TRPM8, mRNA in the spared L4 DRG neurons. Furthermore, intrathecal infusion of antisense oligonucleotide for TRPA1, but not TRPM8, suppressed inflammation-and nerve injury-induced cold hyperalgesia. These data strongly suggest that TRPA1 is the main contributor for cold hypersensitivity in abnormal pain conditions.
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