期刊
NEUROPHARMACOLOGY
卷 67, 期 -, 页码 57-65出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2012.10.030
关键词
Pain; C-C chemokine receptor 5; Mu-opioid receptor; Periaqueductal gray; Naloxone
资金
- Priority Research Centers Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2009-0094035]
- National Research Foundation of Korea (NRF)
- Korea Government (MEST) (MRC) [2010-0029480]
Chemokines are small chemotactic cytokines that elicit many physiological and pathological effects through binding to their corresponding receptors. Recent studies have suggested that C-C chemokine receptor (CCR) 5 interacts with mu-opioid receptor and modifies a nociceptive reaction. We examined effects of CCR5 deficiency on pain responses by employing CCR5 knockout (KO) mice. We found that pain responses of CCR5 KO mice to chemical or inflammation stimuli were milder than those of CCR5 wild type (WT) mice. However, there was no remarkable change in thermal nociception. To prove the involvement of CCR5 deletion in lowered nociception, we examined pain reactions with CCR5 WT mice following treatment of a CCR5 antagonist (D-Ala(1)-peptide T-NH2, DAPTA). Chemical or inflammatory pain behavior was significantly relieved by intracerebroventricular infusion of the inhibitor. When we assessed expression level of mu-opioid receptor (MOR) in the periaqueductal gray where the receptors are critical for analgesic effects, immunoreactivity of MOR was significantly higher in CCR5 KO mice than WT mice without change in phosphorylation level of the receptor. Reduced nociceptive responses in CCR5 KO mice were moderated by administration of naloxone and d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), MOR antagonists. Our data indicate that CCR5 deficiency is related to up-regulation of MOR without an increase in the receptor desensitization which might result in increased analgesic effects against chemical or inflammatory stimuli. Alternatively, higher amount of opioid ligands in CCR5 mice might be linked to these results. Therefore, CCR5 appears to be a therapeutic target for treatment of pain related diseases such as inflammatory hyperalgesia. (c) 2012 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据