Molecular Pain | |
(-)-Pentazocine induces visceral chemical antinociception, but not thermal, mechanical, or somatic chemical antinociception, in μ-opioid receptor knockout mice | |
Kazutaka Ikeda4  Ichiro Sora1  Masamichi Satoh2  George R Uhl5  Masabumi Minami3  Soichiro Ide4  | |
[1] Division of Psychobiology, Department of Neuroscience, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan;Department of Pharmacy, Yasuda Women's University, Hiroshima 731-0153, Japan;Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan;Research Project for Addictive Substances, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan;Molecular Neurobiology, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA | |
关键词: Antinociception; Pentazocine; Knockout mice; Opioid receptor; | |
Others : 866232 DOI : 10.1186/1744-8069-7-23 |
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received in 2011-02-07, accepted in 2011-04-10, 发布年份 2011 | |
【 摘 要 】
Background
(-)-Pentazocine has been hypothesized to induce analgesia via the κ-opioid (KOP) receptor, although the involvement of other opioid receptor subtypes in the effects of pentazocine remains unknown. In this study, we investigated the role of the μ-opioid (MOP) receptor in thermal, mechanical, and chemical antinociception induced by (-)-pentazocine using MOP receptor knockout (MOP-KO) mice.
Results
(-)-Pentazocine-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from the (-)-pentazocine-induced mechanical and somatic chemical antinociception experiments, which used the hind-paw pressure and formalin tests, were similar to the results obtained from the thermal antinociception experiments in these mice. However, (-)-pentazocine retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice, an effect that was completely blocked by pretreatment with nor-binaltorphimine, a KOP receptor antagonist. In vitro binding and cyclic adenosine monophosphate assays showed that (-)-pentazocine possessed higher affinity for KOP and MOP receptors than for δ-opioid receptors.
Conclusions
The present study demonstrated the abolition of the thermal, mechanical, and somatic chemical antinociceptive effects of (-)-pentazocine and retention of the visceral chemical antinociceptive effects of (-)-pentazocine in MOP-KO mice. These results suggest that the MOP receptor plays a pivotal role in thermal, mechanical, and somatic chemical antinociception induced by (-)-pentazocine, whereas the KOP receptor is involved in visceral chemical antinociception induced by (-)-pentazocine.
【 授权许可】
2011 Ide et al; licensee BioMed Central Ltd.
【 预 览 】
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