Modification of Morphine Dependence under Chronic Pain and Its Mechanism
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- SUZUKI Tsutomu
- Department of Toxicology, School of Pharmacy, Hoshi University
Bibliographic Information
- Other Title
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- 慢性疼痛下におけるモルヒネ依存の修飾とその機序
- マンセイ トウツウ カ ニ オケル モルヒネ イゾン ノ シュウショク ト ソノ キジョ
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Abstract
Clinical studies have demonstrated that when opiates are used to control cancer pain, psychological dependence and analgesic tolerance are not a major concern. The present study was, therefore, designed to investigate the modulation of rewarding effects of opiates under inflammatory chronic pain in SD rats. Formalin (2.5%, 50 μl) or carrageenan (1%, 100 μl) was injected into the plantar surface of the rat paw. Formalin and carrageenan reduced the paw pressure threshold. The hyperalgesia lasted for 9 to 13 days. Rewarding effect of morphine was evaluated by conditioned place preference paradigm. Morphine produced a significant place preference. This effect was significantly attenuated in inflamed groups as compared with the respective non-inflamed groups. Furthermore, the morphine-induced place preference in the inflamed group gradually recovered to the respective control level as the inflammation healed. On the other hand, we found that κ-opioid receptor agonists markedly inhibit rewarding effect of μ-opioid receptor agonists. Therefore, to elucidate the mechanism of this attenuation, the effects of pretreatment with κ- and δ-opioid receptor antagonists, nor-binaltorphimine (nor-BNI) and naltrindole (NTI), on the development of the morphine-induced place preference under inflammation were examined. Nor-BNI, but not NTI, eliminated the suppression of the morphine-induced place preference in inflamed groups. The morphine-induced increase in dopamine turnover in the limbic forebrain was suppressed under inflammation, and the suppression was abolished by the pretreatment with nor-BNI. These results suggest that endogenous κ-opioid systems may be activated by chronic inflammatory nociception, resulting in the suppression of the development of rewarding effects produced by morphine.
Journal
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- YAKUGAKU ZASSHI
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YAKUGAKU ZASSHI 121 (12), 909-914, 2001-12-01
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282681104405760
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- NII Article ID
- 110003648498
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- NII Book ID
- AN00284903
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- COI
- 1:CAS:528:DC%2BD3MXovFWqtr8%3D
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- ISSN
- 13475231
- 00316903
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- NDL BIB ID
- 5992355
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- PubMed
- 11766405
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed