The periaqueductal gray contributes to bidirectional enhancement of antinociception between morphine and cannabinoids.
The periaqueductal gray contributes to bidirectional enhancement of antinociception between morphine and cannabinoids.
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DOI：
10.1016/j.pbb.2012.10.002
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发表时间：
2013-01
影响因子：
3.6
通讯作者：
Morgan, Michael M.
中科院分区：
文献类型：
--
作者：
Wilson-Poe, Adrianne R.;Pocius, Edvinas;Herschbach, Melissa;Morgan, Michael M.
阿片类药物和大麻素的联合给药可以增强疼痛缓解，即使在不同的日子给药。已显示重复全身施用吗啡增强12小时后施用的四氢大麻酚（THC）的抗伤害感受作用，并且已显示将大麻素受体激动剂HU-210重复显微注射到腹外侧导水管周围灰质（PAG）中增强一天后施用的吗啡的抗伤害感受作用。本研究的主要目的是测试大麻素/阿片类药物相互作用是双向的假设。实验1表明，每天两次向雄性Sprague-Dawley大鼠的腹外侧PAG中微量注射吗啡，持续2天，增强了一天后测量的HU-210的抗伤害性作用。在实验2中，每天两次全身注射THC增强了一天后施用的吗啡的抗伤害性作用。这些结果补充了先前提到的研究，表明吗啡和大麻素的相互作用是双向的，腹外侧PAG在这种作用中起着重要作用。与PAG相反，将HU-210或大麻素受体激动剂WIN 55，212 -2重复给予RVM具有神经毒性作用。大鼠在重复给予大麻素后生病，无论是单独给予还是与吗啡一起给予。据推测，这种神经毒性作用是由RVM显微注射后的高大麻素浓度引起的，因为大鼠在重复全身性THC给药后没有生病。这些发现表明，交替阿片类药物和大麻素治疗可以产生比单独给予任何化合物更持久和更有效的镇痛作用。
Co-administration of opioids and cannabinoids can enhance pain relief even when administered on different days. Repeated systemic administration of morphine has been shown to enhance the antinociceptive effect of tetrahydrocannbinol (THC) administered 12 hours later, and repeated microinjection of the cannabinoid receptor agonist HU-210 into the ventrolateral periaqueductal gray (PAG) has been shown to enhance the antinociceptive effect of morphine administered one day later. The primary objective of the present study was to test the hypotheses that this cannabinoid/opioid interaction is bidirectional. Experiment 1 showed that microinjection of morphine into the ventrolateral PAG of male Sprague-Dawley rats twice daily for 2 days enhanced the antinociceptive effect of HU-210 measured one day later. In Experiment 2, twice daily systemic injections of THC enhanced the antinociceptive effect of morphine administered one day later. These results complement the previously mentioned studies by showing that morphine and cannabinoid interactions are bidirectional and that the ventrolateral PAG plays an important role in this effect. In contrast to the PAG, repeated administration of HU-210 or the cannabinoid receptor agonist, WIN 55,212-2, into the RVM had a neurotoxic effect. Rats became ill following repeated cannabinoid administration whether given alone or with morphine. Presumably, this neurotoxic effect was caused by the high cannabinoid concentration following RVM microinjection because rats did not become ill following repeated systemic THC administration. These findings indicate that alternating opioid and cannabinoid treatment could produce a longer lasting and more potent analgesia than either compound given alone.
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影响因子：
3.4
作者：
Finn, DP;Beckett, SRG;Chapman, V
通讯作者：
Chapman, V
影响因子：
2.9
作者：
Lane, DA;Morgan, MM
通讯作者：
Morgan, MM
影响因子：
5.5
作者：
Connor, M;Christie, MJ
通讯作者：
Christie, MJ
影响因子：
5
作者：
Cichewicz, DL;Welch, SP;Smith, FL
通讯作者：
Smith, FL
DOI：
10.1124/jpet.102.045575
发表时间：
2003-03-01
影响因子：
3.5
作者：
Cichewicz, DL;McCarthy, EA
通讯作者：
McCarthy, EA