2000 Fiscal Year Final Research Report Summary
The mechanism of hyperalgesia in duced by NMDA receptor activation.
| Project/Area Number |
10671430
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | University of the Ryukyus |
|---|
Principal Investigator |
HIGA Yasutoshi University of the Ryukyus, Department of Anesthesiology, assistant., 医学部・附属病院, 助手 (00228701)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKARA Itaru University of the Ryukyus, Department of Anesthesiology, assistant., 医学部, 助手 (60305208)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Keywords | NMDA / MK-801 / GLUTAMATE / SPINAL CORD / RAT / HYPERALGESIA |
|---|
| Research Abstract |
Bolus injection of N-methyl-D-aspartate (NMDA) in to the intrathecal (IT) space of rat produces short lasting thermal hyperalgesia with pain behavior represented by vocalization, scratching and biting. These behavioral effects after IT injection of NMDA impedes the testing of the pain threshold of the paw. Moreover, the short lasting hyperalgesia kept us from examining the post treatment effect of any drugs after onset of the hyperalgesic state. To produce long lasting thermal hyperalgesia with little pain behavior, we applied continuous intrathecal infusion of NMDA in the rat. To evaluate the character of this model, effects of pre or post-treatment of MK801, a non-competitive NMDA antagonist, on the hyperalgesia, and gluatamate concentration in cerebro spinal fluid were tested. Method : Male Sprague-Dawley rats were used. IT catheters and loop catheters for microdyalysis were implanted according to the Yaksh method. Five to seven days after the surgery, NMDA (0,60,120,180 pmol/min) w
… More
ere continuously infused through the IT catheter by the flow rate of 1μl/min for 30min, followed by 5 minutes interval assessment of paw thermal withdrawal latency (TWL) in response to light heat for 45 minutes. Experiments were performed according to a protocol approved by the Animal Care Committee of the University of the Ryukyus. Results : TWL in the 120 and 180 p mol/min groups were reduced 27.7% and 32.8% from the control value, respectively, 10 minutes after starting the IT infusion. Maximum reduction of TWL appeared after 25 minutes in both groups, and recovered 10 minutes after the infusion was terminated. MK-801 (non-competitive NMDA antagonist) injected prior to NMDA infusion completely abolish this hyperalgesia. However, MK-801 reduced the efficacy when given after established the hyperalgesia by NMDA infusion. Glutamate concentration in CSF was reduced by MK-801 when given prior to NMDA infusion.
Conclusion : Continuous IT infusion of NMDA produced long lasting thermal hyperalgesia, which was dose dependent. The efficacies of MK-801 on hyperalgesia and glutamete concentration in CSF were reduced when given after established the hyperalgesia by NMDA activation. Less
|
