Development of novel Nav1.7 antagonist by using molecular pharmacological methods
| Project/Area Number |
18K08852
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 55050:Anesthesiology-related
|
|---|
| Research Institution | Shinshu University |
|---|
Principal Investigator |
Ishida Takashi 信州大学, 学術研究院医学系(医学部附属病院), 講師 (60531952)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
清澤 研吉 信州大学, 医学部附属病院, 助教(特定雇用) (50624772)
木村 忠史 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (60344214)
中田 勉 信州大学, 学術研究院総合人間科学系, 准教授 (70452141)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 痛み / 局所麻酔薬 / ナトリウムチャネル |
|---|
| Outline of Final Research Achievements |
Congenital insensitivity to pain is a rare autosomal-recessive disorder. Congenital insensitivity to pain is caused by mutations in the gene encoding for the Nav1.7 channel. We analyzed the DNA from the patient who had no pain perception and a novel mutation in SCA9A was detected. The mutation of SCA9A encoded the pore of Nav1.7 channel. We investigated the mutated Nav1.7 function by electrophysiological method. The result suggests decreased ramp current might contribute to insensitivity to pain. We also created the point mutation knock in mice and investigated the behavior to nociceptive stimuli and the channel function of mutated Nav1.7 at dorsal root ganglion. The knock in mice had reduced pain perception to heat and mechanical stimuli and the amplitude of the current produced by mutated Nav1.7 was decreased.
|
| Academic Significance and Societal Importance of the Research Achievements |
痛みは体の異常や危険を察知するために重要な感覚であるが、手術や疾患による過剰な痛みは不快感を与えるだけでなく日常生活に支障をきたすこともある。今回、新しい鎮痛薬のターゲットを見つけるにあたって無痛症患者が痛みを感じない機序を調べた。無痛症患者では電位依存性ナトリウムチャネル（Nav1.7）の機能が低下していることが明らかとなり、このNav1.7をターゲットとすれば安全かつ効果的な鎮痛薬の開発が行える可能性があることが示された。
|
Report
(4 results)
Research Products
(8 results)
