| Project/Area Number |
12470498
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SATOH Masamchi Kyoto University, Grad. Sch. of Pharmaceu. Sci., Professor, 薬学研究科, 教授 (80025709)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Takayuki Kyoto University, Grad. Sch. of Pharmaceu. Sci., Instructor, 薬学研究科, 助手 (30303845)
MINAMI Masabumi Kyoto University, Grad. Sch. of Pharmaceu. Sci., Assistant Professor, 薬学研究科, 助教授 (20243040)
SAJI Hideo Kyoto University, Grad. Sch. of Pharmaceu. Sci., Professor, 薬学研究科, 教授 (40115853)
宮武 伸一 大阪医科大学, 医学研究科, 助教授 (90209916)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2001: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2000: ¥10,500,000 (Direct Cost: ¥10,500,000)
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| Keywords | Basolateral amygdala / Central amygdala / Affective component of pain / Pain / c-fos / Condtioned place aversion / Morphine / Glutamate |
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| Research Abstract |
We investigated the role of the amygdala in sensory and negative affective components of the pain experience in rats. We found that somatic noxious stimulus by intraplanter injection of formalin increased c-fos mRNA expression in lateral (LaA) and basolateral (BLA) nuclei of the amygdala, while visceral noxious stimulus by intraperitoneal injection of acetic acid induced c-fos mRNA especially in the central nucleus of the amygdala (CeA). Both somatic and visceral noxious stimuli produced aversive avoidance behavior from the environment associated with them (conditioned place aversion (CPA)). The somatic noxious stimulus-induced CPA was abolished by the both excitotoxic lesion of BLA and CeA, while visceral noxious stimulus-induced CPA was abolished by the lesion of CeA, but not BLA. These results suggest somatic and visceral noxious stimuli activated different subnuclei of the amygdala,and produce negative affective cpmponents of pain via different mechanisms.
On the other hand, microinjection of morphine into the bilateral BLA not only produced antinociceptive effects in the paw pressure test and formalin test, but also decreased formalin stimulus-induced CPA in dose-dependent manner. Both effects of morphine were antagonized by co-treatment of naloxone. In vivo microdialysis study revealed that formalin stimulus increased extracellular glutamate level in BLA, and the increase was suppressed by morphine treatment in BLA. Furthermore, microin-jection of NMDA receptor antagonist MK-801, but not non-NMDA receptor antagonist CNQX nor metabotropic glutamate receptor antagonist AP-3, into the bilateral BLA decreased formalin stimulus-induced CPA, while these glutamate antagonists had no effect on formalin-induced noxious behavior.These results suggest that |l-opioid receptors within BLA are involved in the regulation of sensory and negative affective components of pain by inhibiting glutamatergic system in BLA.
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