Involvement of receptor-mediated regulation of Ca channel and second messengers in pain transmission and modulation
| Project/Area Number |
04454388
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
麻酔学
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
ISHIKAWA Toshizoh Yamaguchi Univ. Research School of Med. Associate, 医学部, 助手 (90034991)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KURODA Yasuhiro Yamaguchi Univ. Research Hospital Associate, 医学部・附属病院, 助手 (80234615)
NAKAKIMURA Kazuhiko Yamaguchi Univ. Research School of Med. Associate, 医学部, 助手 (50180261)
MAEKAWA Tsuyoshi Yamaguchi Univ. Professor Hospital, 医学部・附属病院, 教授 (60034972)
SAKABE Takefumi Yamaguchi Univ. Professor School of Med., 医学部, 教授 (40035225)
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥3,200,000 (Direct Cost: ¥3,200,000)
|
|---|
| Keywords | Analgesia / Tolerance / Spinal cord / G Protein / Adenylate cyclase / Protein kinase C / Ca channel / Nitric oxide / NMDA antagonist / N-type Ca channel / α2-receptor / Intracellular spinal transduction / 鎮痛 / 耐性発現 / オピオイド / モノアミン / α_2受容体 / 情報伝達系 / G蛋白質 / アデニル酸シクラーゼ |
|---|
| Research Abstract |
The intracellular signal transducing(ICST) system has recently been suggested to play an important role in pain transmission and modulation. The present study was undertaken to examine whether N20 analgesia is mediated the activities of Ca channel and 2nd messenger systems inb the rat spinal cord. Inaddition, we examined possibel involvement of these activities o fICST systems in inflammatory responses.
Wistar rats were exposed to 75% N20. N20 produced analgesia assessed by tail-flick latency. However, this effect was reduced during second exposure sullggesting the development of acute tolerance.
At the end of the first exposure, 3H-clonidine (alpha-2 receptor) binding by using in vitro autoradiography icreased accompanied by both decreases in 3H-forskolin(adenylate cyclase) and 125I- CgTX(N-type Ca channel)bindings. At the end of second exposure these bindings returned to the control levels, while 3H-PDBu(protein kinase C) increased. This acute tolerance was inhibited by Ca channel antagonist, NMDA antagoist, and inhibitor of nitric oxide (NO) synthase. In inflammatory study, the increase in neuronal activities(glucose utilization) was accomanied with receptor(NK-1, NMDA)-mediated activation of both voltage dependent Ca channel(3H-PN 200-110 binding) and phospholiration of protein(3H-PDBu binding) at laminae 1-2 of dorsal horn after injection of mustard oil. L-type Ca channel antagonist and NMDA receptor antagonist suppressed painrelated behavior and alteration in signal transducing systems.
These results suggest that the receptor (NK-1, NMDA ; alpha-2, mu)-mediated regulation of Ca channel and 2nd messenger systems, interacting with protein kinase C and NO-cGMP systems, are involved in pain transmission and modulation.
|
Report
(3 results)
Research Products
(13 results)
