Relative contribution of the dorsal raphe nucleus and ventrolateral periaqueductal gray to morphine antinociception and tolerance in the rat.
Relative contribution of the dorsal raphe nucleus and ventrolateral periaqueductal gray to morphine antinociception and tolerance in the rat.
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DOI：
10.1111/ejn.13378
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Morgan MM
中科院分区：
文献类型：
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作者：
Campion KN;Saville KA;Morgan MM
中缝背核（DRN）位于中脑导水管周围灰质（PAG）的腹侧。电或化学激活整个区域的神经元产生抗伤害感受。本手稿的目的是确定腹外侧PAG和DRN是否是不同的抗伤害性系统。通过确定将吗啡微注射到每个结构中的抗伤害感受效力（实验1），创建产生抗伤害感受的有效微注射位点的地图（实验2），并将抗伤害感受耐受性的发展与将吗啡重复微注射到腹外侧PAG和DRN中进行比较（实验3），来测试该假设。吗啡累积注射（1.0、2.2、4.6和10 μg/0.2 μl）到PAG腹外侧（D_（50）= 3.3 μg）比外侧（4.3 μg）或内侧（5.8 μg）DRN更有效。94%的吗啡注射到PAG腹外侧后产生抗伤害感受，而只有68.3%和78.3%的注射到DRN的外侧和内侧产生抗伤害感受。重复微量注射吗啡到腹外侧PAG产生的耐受性表明吗啡和生理盐水预处理大鼠之间的效力的528%的差异。与此相反，相对较小的变化发生在重复微量注射吗啡到外侧和内侧方面的DRN（107%和49%，分别）。这些数据表明，腹外侧PAG和DRN是不同的抗伤害性结构。与DRN相比，腹外侧PAG注射的抗伤害性更强，但由于耐受性的发展，这种抗伤害性很快消失。微量注射吗啡产生更大的抗伤害性和更大的耐受性，这种抗伤害性注射到腹外侧中脑导水管周围灰质（PAG）相比，中缝背核（DRN）的外侧或内侧方面。这些数据表明，腹外侧PAG和相邻的DRN是不同的疼痛调制系统。
The dorsal raphe nucleus (DRN) is embedded in the ventral part of the caudal periaqueductal gray (PAG). Electrical or chemical activation of neurons throughout this region produces antinociception. The objective of this manuscript is to determine whether the ventrolateral PAG and DRN are distinct antinociceptive systems. This hypothesis was tested by determining the antinociceptive potency of microinjecting morphine into each structure (Experiment 1), creating a map of effective microinjection sites that produce antinociception (Experiment 2), and comparing the development of antinociceptive tolerance to repeated microinjections of morphine into the ventrolateral PAG and DRN (Experiment 3). Morphine was more potent following cumulative injections (1.0, 2.2, 4.6, &10 μg/0.2 μl) into the ventrolateral PAG (D50 = 3.3 μg) compared to the lateral (4.3 μg) or medial DRN (5.8 μg). Antinociception occurred following 94% of the morphine injections into the ventrolateral PAG, whereas only 68.3% and 78.3% of the injections into the lateral and medial aspects of the DRN produced antinociception. Repeated microinjections of morphine into the ventrolateral PAG produced tolerance as indicated by a 528% difference in potency between morphine and saline pretreated rats. In contrast, relatively small changes in potency occurred following repeated microinjections of morphine into the lateral and medial aspects of the DRN (107% and 49%, respectively). These data indicate that the ventrolateral PAG and DRN are distinct antinociceptive structures. Antinociception is greater with injections into the ventrolateral PAG compared to the DRN, but this antinociception disappears rapidly because of the development of tolerance. Microinjection of morphine produced greater antinociception and greater tolerance to this antinociception following injections into the ventrolateral periqueductal gray (PAG) compared to the lateral or medial aspects of the dorsal raphe nucleus (DRN). These data indicate that the ventrolateral PAG and adjacent DRN are distinct pain modulatory systems.