Murphy Anne Z, Behbehani Michael M
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267 USA.
Pain. 1993 Nov;55(2):183-193. doi: 10.1016/0304-3959(93)90147-H.
We have previously demonstrated that the nucleus raphe magnus (NRM) sends a predominantly inhibitory projection to the lateral reticular nucleus (LRN); however, the pharmacology of this pathway is not known. The purpose of this study was to examine the role of norepinephrine in the NRM-LRN system using both electrophysiological and behavioral techniques. Sixty-nine LRN cells were recorded extracellularly. Cells were tested for their response to noxious and innocuous peripheral stimulation applied to the dorsal body surface. The majority of cells were classified as wide dynamic range, with inhibition being the predominant response; receptive fields were located primarily on the tail and hind limbs. The effect of excitatory amino acid glutamate (GLU) administration into NRM (GLU-NRM) was tested on all 69 cells. GLU-NRM inhibited 55 of 69 LRN cells tested; 7 cells were excited and 7 cells did not respond. Thirty-nine LRN cells were tested for their response to norepinephrine (NE) iontophoretically applied in LRN (NE-LRN). Two distinct types of effects were noted. In 9 cells, both NE-LRN and GLU-NRM produced a strong inhibition, with the magnitude of effect between the 2 drugs significantly correlated. In a second group of cells (n = 12), GLU-NRM produced an inhibitory effect while NE-LRN had no effect on the cells' baseline firing rate. However, when the 2 drugs were applied simultaneously, NE-LRN blocked the inhibitory effects of NRM stimulation. The effect of the alpha 2-receptor antagonist yohimbine (YOH) on NRM-evoked responses was tested in 30 LRN cells. The majority of these cells were inhibited by GLU-NRM. Similar to the dichotomous effect noted by NE-LRN, YOH applied iontophoretically in LRN (YOH-LRN) had two predominant effects on NRM-produced inhibition. In 14 of 27 cells, YOH-LRN significantly potentiated the inhibitory effects of NRM stimulation by increasing the duration of the inhibitory epoch an average of 100 sec. In 7 of 27 cells, YOH directly applied in LRN partially antagonized NRM-evoked inhibition. In a second series of experiments, microinjection cannulas were placed within NRM and LRN in order to determine the effect of blocking alpha 2-receptor activity within LRN on NRM stimulation-produced analgesia in an intact animal. Administration of D,L-homocysteic acid in NRM resulted in a significant increase in baseline tail-flick latency of approximately 140%. Pretreatment with YOH (3 micrograms in 0.5 microliter) in LRN resulted in a significant potentiation of this analgesic effect.(ABSTRACT TRUNCATED AT 400 WORDS)
我们之前已经证明，中缝大核（NRM）向外侧网状核（LRN）发出主要为抑制性的投射；然而，该通路的药理学情况尚不清楚。本研究的目的是使用电生理学和行为学技术来研究去甲肾上腺素在NRM-LRN系统中的作用。对69个LRN细胞进行了细胞外记录。测试这些细胞对施加于背部体表的有害和无害外周刺激的反应。大多数细胞被归类为广动力范围，抑制是主要反应；感受野主要位于尾部和后肢。对所有69个细胞测试了向NRM注射兴奋性氨基酸谷氨酸（GLU）（GLU-NRM）的效果。GLU-NRM抑制了69个测试的LRN细胞中的55个；7个细胞被兴奋，7个细胞无反应。对39个LRN细胞测试了通过离子导入法在LRN中施加去甲肾上腺素（NE）（NE-LRN）后的反应。观察到两种不同类型的效应。在9个细胞中，NE-LRN和GLU-NRM均产生强烈抑制，两种药物的效应大小显著相关。在第二组细胞（n = 12）中，GLU-NRM产生抑制作用，而NE-LRN对细胞的基础放电率无影响。然而，当同时应用这两种药物时，NE-LRN阻断了NRM刺激的抑制作用。在30个LRN细胞中测试了α2受体拮抗剂育亨宾（YOH）对NRM诱发反应的影响。这些细胞中的大多数被GLU-NRM抑制。与NE-LRN观察到的二分效应相似，在LRN中离子导入应用YOH（YOH-LRN）对NRM产生的抑制有两种主要效应。在27个细胞中的14个中，YOH-LRN通过将抑制期的持续时间平均增加100秒，显著增强了NRM刺激的抑制作用。在27个细胞中的7个中，直接在LRN中应用YOH部分拮抗了NRM诱发的抑制。在第二系列实验中，将微量注射套管置于NRM和LRN内，以确定阻断LRN内α2受体活性对完整动物中NRM刺激产生的镇痛作用的影响。在NRM中给予D，L-高半胱氨酸导致基线甩尾潜伏期显著增加约140%。在LRN中用YOH（0.5微升中含3微克）预处理导致这种镇痛作用显著增强。（摘要截断于400字）
