Mei Jianfeng, Pasternak Gavril W
The Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 1002, USA.
J Pharmacol Exp Ther. 2007 Sep;322(3):1278-85. doi: 10.1124/jpet.107.121137. Epub 2007 Jun 1.
sigma(1) Receptors have been implicated in the modulation of opioid analgesia. In the current study, we examined the role of sigma(1) systems in the periaqueductal gray (PAG), the rostroventral medulla (RVM), and the locus coeruleus (LC) of the rat, regions previously shown to be sensitive to morphine. Morphine was a potent analgesic in all three regions. Coadministration of the sigma(1) agonist (+)-pentazocine diminished the analgesic actions of morphine in all three regions, although the PAG was far less sensitive than the other two regions. Blockade of the sigma(1) receptors with haloperidol in the RVM markedly enhanced the analgesic actions of coadministered morphine, implying a tonic activity of the sigma(1) system in this region. This effect was mimicked by down-regulation of RVM sigma(1) receptors using an antisense approach. However, no tonic sigma(1) activity was observed in either the LC or the PAG. The RVM also was important in modulating analgesia elicited from morphine microinjected into the PAG. The analgesic actions of morphine given into the PAG could be attenuated by (+)-pentazocine placed into the RVM, whereas haloperidol in the RVM enhanced PAG morphine analgesia. These studies illustrate the pharmacological importance of sigma(1) receptors in the brainstem modulation of opioid analgesia.
σ1受体与阿片类镇痛的调节有关。在本研究中，我们研究了σ1系统在大鼠导水管周围灰质（PAG）、延髓头端腹内侧区（RVM）和蓝斑（LC）中的作用，这些区域先前已被证明对吗啡敏感。吗啡在所有这三个区域都是一种强效镇痛药。σ1激动剂（+）-喷他佐辛与吗啡共同给药会减弱吗啡在所有这三个区域的镇痛作用，尽管PAG的敏感性远低于其他两个区域。在RVM中用氟哌啶醇阻断σ1受体可显著增强共同给药的吗啡的镇痛作用，这意味着该区域的σ1系统存在紧张性活动。使用反义方法下调RVM的σ1受体可模拟这种效应。然而，在LC或PAG中均未观察到σ1的紧张性活动。RVM在调节由微量注射到PAG中的吗啡所引发的镇痛方面也很重要。注入RVM的（+）-喷他佐辛可减弱注入PAG的吗啡的镇痛作用，而RVM中的氟哌啶醇则增强PAG吗啡的镇痛作用。这些研究说明了σ1受体在脑干对阿片类镇痛的调节中的药理学重要性。
