1996 Fiscal Year Final Research Report Summary
Modulation of the development of tolerance to morphine by NOSI
| Project/Area Number |
07671662
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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 | Shimane Medical University |
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Principal Investigator |
KIRIHARA Yumiko Shimane Medical University, Anesthesiology, Technical Official, 医学部, 教務職員 (90234400)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yoji Shimane Medical University, Anesthesiology, Associate Professor, 医学部, 助教授 (50162243)
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| Project Period (FY) |
1995 – 1996
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| Keywords | morphine / NO / tolerance / spinal |
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| Research Abstract |
Two intrathecal catheters were implanted in the subarachnoid space in male Sprague-Dawley rats under anesthesia. One of the following regimens was infused in a double blind fashion ; 1) morphine ; 1 mug/kg/hr (M1) or 5 mug/kg/hr (M5), 2) ketamine ; 250 mug/kg/hr (K250), 3) L-NAME 15 mug/kg/hr (NA15), 4) L-NMMA ; 30 mug/kg/hr (NM30), 5) combination of those ; morphine 5 mug/kg/hr+ketamine 250 mug/kg/hr (M5K250), morphine 5 mug/kg/hr+L-NAME 15 mug/kg/hr (M5NA15), morphine 5 mug/kg/hr+L-NMMA 30 mug/kg/hr (M5NM30) and 4) saline (S). Tail flick (TF) test and colorectal distension (CD) test were employed to measure responses to noxious somatic and visceral stimuli, respectively. Measurements were performed every day for 7days and a challenge test with intrathecal morphine 5 mug was done to assess the development of morphine tolerance on day 7.
M5, but not M1, increased the %MPEs in TF test to 60% and 80%, and the %MPEs in CD test increased to 40% and 46%, respectively, on day 1 or day 2. K250, NA15, and NM30 did not increase %MPEs in neither tests. M5NA15 increased the %MPEs to 50% on day 3 and 30% on day 4 in TF test and to 30% and 25% in CD test, respectively. M5K increased the %MPEs in both TF and CD to 90%. M5 produced significant decrease %MPEs compared with S in morphine challenge test. However, the decreases in %MPEs were inhibited following the M5NA15, M5NM30, or M5K250 infusion.
NOSI and NMDA receptor antagonists increased the somatic and visceral antinociception of morphine and attenuated the development of morphine tolerance to those antinociceptive effects.
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