2010 Fiscal Year Final Research Report
Sensitization of DRG neurons by inflammatory mediators
| Project/Area Number |
20602017
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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 |
疼痛学
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| Research Institution | Hyogo University of Health Sciences |
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Principal Investigator |
DAI Yi Hyogo University of Health Sciences, 薬学部, 准教授 (20330441)
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| Project Period (FY) |
2008 – 2010
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| Keywords | TRPA1 / P2X3 / PAIN / Inflammation |
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| Research Abstract |
The TRPA1/P2X3 ion channel is localized on nociceptors of sensory neurons. Both bradykinin receptor 2 (B2R) or Proteinase-activated receptor-2 (PAR-2) are expressed in a subset of primary afferent neurons and is involved in inflammatory nociception. In this study, the functional interaction of the B2R or PAR-2 and TRPA1/P2X3, was investigated by morphological, molecular-biological and electrophysiological analyses in rat dorsal root ganglion (DRG) neurons or HEK cells transfected with TRPA1 or P2X_3. We found that many TRPA1s or P2X_3s were functionally co-expressed with the B2R or PAR-2 in rat DRG neurons. Using whole-cell patch clamp technique, we observed that B2R/PAR-2 activation increased the TRPA1/P2X currents evoked by allyl isothiocyanate or alpha beta-methylene adenosine 5'-triphosphate in DRG neurons, respectively. Inhibitors of phospholipase C (PLC), or protein kinase A (PKA) suppressed these potentiations. Application of a PLC activator or a PKA activator mimicked the B2R/PAR-2 mediated potentiation of TRPA1 or P2X current, respectively. Thus, the increased TRPA1 or P2X sensitivity may be due to the activation of PLC and/or PKA, which are downstream of the B2R and PAR-2 signal. These findings indicate that in inflammatory disease, Bradykinin or PAR-2 agonists may potentiate TRPA1 or P2X_3 ion channels to induce pain ; the mechanism of this potentiation is likely to be a result of activation of PLC or PKA signals.
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[Journal Article] Activation of extracellular signal-regulated protein kinase in sensory neurons after noxious gastric distention and its involvement in acute visceral pain in rats2008
Author(s)
Sakurai J, Obata K, Ozaki N, Tokunaga A, Kobayashi K, Yamanaka H, Dai Y, Kondo T, Miyoshi K, Sugiura Y, Matsumoto T, Miwa H, Noguchi K
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Journal Title
Gastroenterology 134(4)
Pages: 1094-103
Peer Reviewed
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