Lim Grewo, Wang Shuxing, Mao Jianren
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.
Brain Res. 2005 Oct 12;1059(1):20-7. doi: 10.1016/j.brainres.2005.08.002. Epub 2005 Sep 16.
Central cannabinoid receptors (CBRs) have been implicated in the opioid analgesic effects. However, it remains unclear as to whether the expression of central CBRs would be altered after repeated morphine exposure. Here, we show that chronic intrathecal treatment with morphine (10 microg, twice daily for 6 days) induced a time-dependent upregulation of both CB-1 and CB-2 receptors within the spinal cord dorsal horn. This morphine-induced CB-1 and CB-2 upregulation was dose-dependently attenuated by the intrathecal co-administration of morphine with the glucocorticoid receptor (GR) antagonist RU38486 (0.25, 0.5, or 2 microg). The intrathecal RU38486 treatment regimen also attenuated the development of morphine tolerance. These results indicate that the expression of spinal CBRs was altered following repeated morphine exposure and regulated by the activation of central GRs.
中枢大麻素受体（CBRs）与阿片类药物的镇痛作用有关。然而，反复暴露于吗啡后中枢CBRs的表达是否会发生改变仍不清楚。在此，我们发现，慢性鞘内注射吗啡（10微克，每日两次，共6天）可诱导脊髓背角内CB-1和CB-2受体的时间依赖性上调。鞘内联合给予吗啡与糖皮质激素受体（GR）拮抗剂RU38486（0.25、0.5或2微克）可剂量依赖性地减弱这种吗啡诱导的CB-1和CB-2上调。鞘内注射RU38486的治疗方案也减弱了吗啡耐受性的发展。这些结果表明，反复暴露于吗啡后脊髓CBRs的表达发生了改变，并受中枢GRs激活的调节。
