中缝大核内神经降压素在痛觉调制中的作用

目的:探讨中缝大核(NRM)内神经降压素(NT)在痛觉调制中的作用,及其和内源性5-HT在痛觉调制中的关系.方法:以钾离子透入法引起大鼠甩尾反应的电流强度(mA)为痛反应指标,测定动物痛阈,观察NRM内神经降压素对大鼠痛阈的影响.结果:NRM内注入神经降压素后,大鼠的痛阈明显增加,并在一定范围内呈明确的剂量-效应关系;注入抗神经降压素血清或NT拮抗剂后,大鼠的痛阈则明显降低.NRM内注入噻庚啶后,可阻断NT镇痛的效应.结论:NRM内的神经降压素在痛觉调制的复杂过程中发挥着一定作用,且其效应是通过内源性5-HT系统中介的.     

家兔部分脑区及血浆神经降压素在降压反射中的变化

实验分别采用颈动脉窦流及电刺激减压神经的方法，测定在产生减压效应时，家兔部分脑区及血浆内神经降压素含量的改变，结果表明，颈动脉窦灌流及电刺激减压神经产生明显的减压效应时，家兔垂体，下丘脑，延髓及血浆内神经降压素含量较对照组明显增高，该结果提示，家兔体内源性神经降压素可能参与和感受性反射的调节过程。     

中枢神经系统一氧化氮对大鼠的痛觉调制作用

以钾离子透入引起大鼠甩尾的电流强度（ｍＡ）作为痛反应指标,采用侧脑室微量注射Ｌ－精氨酸（Ｌ－Ａｒｇ）、亚甲基蓝（ＭＢ）等,大鼠痛阈的变化,分析探讨中枢神经系统中一氧化氮（ＮＯ）对大鼠痛觉的调制作用,结果显示：大鼠侧脑室微量注射ＮＯ前体及供体物质Ｌ－Ａｒｇ和硝普钠（ＳＮＰ）均引起明显的痛敏效应。微量注射ＭＢ和Ｌ－ＮＡＭＥ后大鼠痛阈升高非常显著。侧脑室微量注射ＭＢ和Ｌ－Ａｒｇ混合液后,大鼠痛阈较单纯注     

急性颅脑损伤神经降压素含量变化及临床意义

目的和方法应用放免法动态测定51例急性颅脑损伤患者血浆及脑脊液神经降压素含量，以观察神经降压素水平在颅脑损伤组和正常对照组中的变化，并探讨其临床意义。结果颅脑损伤患者急性期血浆及脑脊液神经降压素含量显著高于对照组，且与病情轻重程度明显相关。结论神经降压素参与急性颅脑损伤后继发性病理生理过程；神经降压素受体桔抗剂成为治疗颅脑损伤的有效途径；血浆或脑脊液神经降压素动态含量，可能是判断急性颅脑损伤患者预后的重要因素。     

急性缺血性脑血管病患者血浆神经降压素含量变化的观察

美国生理学家Carraway和Leeman等(1973)从牛的下丘脑提纯P物质时,发现了另一种生物活性物质,能使小鼠的毛细血管通透性增高,皮肤血管扩张及血压下降。由于这种物质位于神经组织,又有降压作用,故称神经降压素(NT)。现已证明NT不仅存在于哺乳动物和人的脑组织,也广泛存在胃肠道及其它组织中,它具有广泛的生物学特性。目前,关于急性缺血性脑血管病(ICVD)患者血浆NT变化报道较少,我们测定了31例ICVD患者血浆NT含     

神经降压素和生长抑素在急性颅脑损伤的临床研究

神经降压素和生长抑素在急性颅脑损伤的临床研究李云辉梁瑞奇杜军成小玲张桂萍刘荣李丽芳王育敏朱蓉一、资料与方法男２２例，女９例，年龄６～６８岁，平均２９．１岁。均于受伤后１２小时内入院。入院时ＧＣＳ≤８分者１３例，ＧＣＳ＞８分者１８例。经ＣＴ或手术证实，...     

脑出血患者血浆神经肽Y和神经降压素的研究

目的：观察脑出血患者浆神经肽Ｙ（ＮＰＹ）和神经降压素（ＮＴ）的水平变化。方法：采用放射免疫方法测定了４６例脑出血患者血浆ＮＰＹ和ＮＴ的含量。结果：血浆ＮＰＹ和ＮＴ水平在发病２４小时内即显著上升,４～７天或１～３天达高峰,８～１５天开始下降,１５天后仍在较高水平。重型患者ＮＰＹ水平显著高于轻型和中型,中、重型患者ＮＴ水平显著高于轻型。结论：ＮＰＹ和ＮＴ参与了脑出血的发生及病理生理过程。     

急性脑血管病患者血浆神经降压素的临床研究

目的 观察脑出血（ＣＨ）、脑梗死（ＣＩ）、蛛网膜下腔出血（ＳＡＨ）患者血浆神经降压素（ＮＴ）水平改变及其动态变化。方法 选择ＣＨ组４６例、ＣＩ组６２例、ＳＡＨ组３０例,用放免法检测血浆ＮＴ浓度。结果 ＣＩ组、ＣＨ组、ＳＡＨ组ＮＴ水平均显著高于对照组,于发病后２４小时内显著升高,１￣３天或４￣７天达高峰,８￣１５天开始下降,１５天后仍在较高水平;随病情加重与病灶扩大显著升高;ＣＩ与ＣＨ伴高血压糖组均显著高于正常血糖组,ＣＨ伴高血压组、伴消化道出血组显著高于正常血压组与无消化道出血组。ＳＡＨ组伴ＤＩＤ组明显高于非ＤＩＤ组。结论 ＮＴ分泌异常参与了ＣＩ、ＣＨ、ＳＡＨ的病理生理过程。     

中枢神经系统一氧化氮对大鼠的痛觉调制作用

以钾离子透入引起大鼠甩尾的电流强度(mA)作为痛反应指标,采用侧脑室微量注射L-精氨酸(L-Arg)、亚甲基蓝(MB)等,观察大鼠痛阈的变化,分析探讨中枢神经系统中一氧化氮(NO)对大鼠痛觉的调制作用.结果显示:大鼠侧脑室微量注射NO前体及供体物质L-Arg和硝普钠(SNP)均引起明显的痛敏效应.微量注射MB和L-NAME后大鼠痛阈升高非常显著.侧脑室微量注射MB和L-Arg混合液后,大鼠痛阈较单纯注射MB组表现出明显降低的趋势,但与L-Arg组相比大鼠痛阈升高明显.提示:提高中枢内NO水平具有明显的痛敏效应,而降低中枢神经系统NO水平表现显著镇痛作用.中枢神经系统NO对大鼠痛觉的调制作用至少部分是通过NO-cGMP途径实现的.     

抗阿片肽血清对中脑导水管周围灰质内神经降压素镇痛作用的影响

本工作以钾离子透入法引起大鼠甩尾反应为痛反应指标，测定动物病阈，发现大鼠中脑导水管周围灰质（PAG）内注入神经降压素（NT）后．大鼠痛阈明显升高；注入抗神经降压素血清后，痛阈明显降低。分别注入纳洛酮、抗甲-脑啡肽血清和抗β-内啡肽血清后，均可明显减弱NT的镇痛效应；注入抗强啡肽血清后，对NT的镇痛效应无显著影响。提示，PAG内NT在痛觉调制中的作用至少部分与PAG内的内源性甲一脑啡肽和β-内啡肽有密切关系。     

The periaqueductal gray-raphe magnus projection contains somatostatin, neurotensin and serotonin but not cholecystokinin

The retrograde transport-HRP-immunocytochemical technique was employed to ascertain if the periaqueductal gray-raphe magnus projection arises from neurons containing somatostatin, neurotensin, serotonin or cholecystokinin. Following HRP injections into the raphe magnus (NRM) double-labeled cells containing HRP reaction product and somatostatin-, neurotensin- or serotonin-like immunoreactivity were identified in the midbrain periaqueductal gray (PAG). No cholecystokinin-like immunoreactive double-labeled neurons were found in the PAG. These results indicate that the PAG-NRM pathway contains somatostatin, neurotensin and serotonin but not cholecystokinin.     

Microinjection of morphine into nucleus reticularis paragigantocellularis of the rat suppresses spontaneous activity of nucleus raphe magnus neurons

Female rats were neonatally treated with estradiol-17 beta-benzoate or the long-acting dibenzoate esters of the isomeric catecholestrogens, 2-hydroxyestradiol-17 beta and 4-hydroxyestradiol-17 beta. Estrogen benzoates were administered subcutaneously from day 1 to 5 of life at doses of 0.05, 0.10, 0.50 and 1.00 micrograms/day. All rats were ovariectomized as adults and, 4 weeks later, the luteinizing hormone (LH) response to progesterone (2.5 mg) was tested after priming with estradiol-17 beta-benzoate (20 micrograms). At a dose of 0.5 micrograms/day, estradiol-17 beta-benzoate and 4-hydroxyestradiol-17 beta-dibenzoate were equally effective in neonatally defeminizing the LH surge mechanism. In contrast, up to a dose of 1.00 micrograms/day, 2-hydroxyestradiol-17 beta-dibenzoate did not interfere with the LH response in adult life. In the pituitary gland and uterus of the neonatally defeminized rats estrogen responsiveness of cytosolic progestin receptor induction was unimpaired. Moreover, in the uterus of these rats nuclear translocation of cytosolic progestin receptors was intact.     

Distributive characteristics of projection from vestibular nuclei to nucleus raphe magnus in rats

BACKGROUND: Morphological studies have confirmed that vestibular nuclei accepts serotoninergic projections from nucleus raphe magnus, nucleus raphes pallidus, etc. But it is still unclear whether there is bi-directional association between vestibular nuclei and nucleus raphe magnus. OBJECTIVE: To observe the characteristics of projective fibers from vestibular nuclei to nucleus raphe magnus using tetramethyl rhodamine (TMR) in rats, so as to provide more sufficient morphological evidence of neural association from vestibular nuclei. DESIGN: An observational experiment. SETTING: Department of Anatomy (K.K. Leung Brain Research Center), the Fourth Military Medical University of Chinese PLA. MATERIALS: Eighteen male SD rats of clean degree, weighing 250-280 g, were provided by the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA. METHODS: The experiments were carried out in the laboratory of Department of Anatomy (K.K. Leung Brain Research Center), the Fourth Military Medical University of Chinese PLA from September 2006 to January 2007. All the rats were anesthetized with intraperitoneal injection of pentobarbital sodium, then according to the coordinates on the rat brain atlas, 0.1 μL TMR (100 g/L) was injected into nucleus raphes magnus via the tip of glass microtubule by means of microinjection. Seven days later, the rats were anesthetized, then perfused and fixed to remove brain, and then frozen coronal brain sections were prepared. The retrogradely labeled neurons in the injected and projected sites were observed under fluorescence microscope. Light filters with evoked wave length of 540-553 nm and emission wave length ≥ 1 580 nm were selected to observe the orange TMR-labeled neurons. All the sections were observed and counted under the fluorescence microscope. MAIN OUTCOME MEASURES: Characteristics and number of retrogradely labeled neurons at different sites of nuclei. RESULTS: Totally 18 SD rats were enrolled, 9 of them were excluded due to the deviation of injected site, and the other 9 were involved in the final analysis of results. The concentrated region of TMR injection was mainly restricted to nucleus raphes magnus, and diffused to the surrounding area to different extents. There were obvious differences in the distributions of the labeled neurons among the subdivisions in vestibular nuclei, as well as the distributions of the labeled neurons at different sites in the same subdivision. The majority of the labeled neurons distributed in the rostral levels of medial vestibular nucleus and the lateral vestibular nucleus, while fewer labeled neurons were observed in superior vestibular nucleus. CONCLUSION: ① There might be bi-directional association between vestibular nucli and nucleus raphe magnus, suggesting that nucleus raphe magnus played a role in the transmission and processing of vestibular information. ② The projection from nucleus raphe magnus to vestibular nucleus has certain distributive characteristics in the region.     

Tooth pulp input to the spinal trigeminal nucleus: A comparison of inhibitions following segmental and raphe magnus stimulation

In rats and cats anaesthetized with urethane a comparison was made of the inhibitory effects of raphe magnus (NRM) and segmental (facial skin) stimulation on neurones in nucleus caudalis excited by tooth pulp stimulation. The upper and lower ipsilateral incisor teeth were used in rats (176 neurones) and the corresponding canine teeth in cats (34 neurones). The recording sites were located in all layer of nucleus caudalis and in the underlying reticular formation. Both the evoked responses and the conditioning effects were similar in the two species. Both forms of conditioning inhibited about half the neurones tested but only a small proportion was influenced from both sources. NRM stimulation had almost identical effects on neurones driven from upper teeth or from lower teeth and tended to act on those cells with longer latencies. Segmental stimulation influenced the majority of shorter latency cells and produced greater inhibitions of upper tooth pulp neurones. Diffuse noxious inhibitory controls were also observed for certain neurones.     

Microinjection of morphine into nucleus reticularis paragigantocellularis of the rat: Suppression of noxious-evoked activity of nucleus raphe magnus neurons

Microinjection of 1 microgram of morphine into nucleus reticularis paragigantocellularis (Pgc) of anesthetized rats depressed both noxious-evoked and spontaneous activity of nociresponsive neurons in the nucleus raphe magnus (NRM). This effect was naloxone-reversible, and was not observed after control injections dorsal to Pgc. The percent change in spontaneous firing was significantly greater than the percent change in pinch-evoked firing. This reduction in NRM neuronal discharge may contribute to the antinociceptive effects produced by microinjection of morphine into Pgc.     

Ascending and cerebellar non-serotonergic projections from the nucleus raphe magnus of the rat

Non-serotonergic ascending and cerebellar projections of rat nucleus raphe magnus (RM) were disclosed using the horseradish peroxidase technique. The ascending bundle rose form rostral RM and was divided into two components; one ascended in raphe regions and the other in reticular formation. The former on innervated n. raphe dorsalis, etc., and the latter n. parafascicularis, zona incerta, etc. On the other hand, the axons innervating neocerebellum originated exclusively from caudal RM.     

The role of acetylcholine in the function of the nucleus raphe magnus and in the interaction of this nucleus with the periaqueductal gray

The nucleus raphe magnus (NRM) plays an important role in the inhibition of pain. Although this region receives afferents from several areas of the brain, the afferent input from the periaqueductal gray (PAG) has been shown to have significant physiological importance. Together, these two sites constitute the major component of a descending network involved in pain inhibition. In this study the role of acetylcholine (ACh) in the function of the NRM was investigated and the possibility that ACh may be a transmitter between the PAG and the NRM was tested. ACh was applied iontophoretically. Scopolamine and gallamine were used to test the type of cholinergic receptors that are present in the NRM. The results of this study shows the following. (1) The majority of the cells in the NRM are excited by ACh. (2) This response to ACh is partially or totally blocked by scopolamine whereas gallamine does not block the response. (3) There is no correlation between the excitatory response to stimulation of PAG and to ACh. There are cells that respond to PAG stimulation by inhibition but are excited by ACh and there are a few cells that are inhibited by ACh but are excited by PAG stimulation. (4) Scopolamine, at a dose that blocks the ACh response, does not block the response to PAG stimulation. (5) There is no correlation between the response to ACh and the type of projection (direct or indirect) to the spinal cord, as tested by stimulation of the dorsolateral funiculus. From these results it is concluded that ACh is an excitatory transmitter at the NRM region but this transmitter does not mediate the interaction between the PAG and NRM.     

The effect of modification of 5-hydroxytryptamine function in nucleus raphe magnus on nociceptive threshold

Thresholds to noxious heat stimulation were increased following microinjection of zimelidine, an inhibitor of 5-hydroxytryptamine (5-HT) re-uptake, into the nucleus raphe magnus (NRM) of rats. Pretreatment with intraperitoneally given cinanserin reduced this effect but pretreatment with intraperitoneally given phenoxybenzamine did not. Fenfluramine, which causes the release of 5-HT from synaptic terminals also elevated nociceptive thresholds following microinjection into NRM. Subanalgesic doses of morphine or zimelidine elevated nociceptive thresholds when microinjected together into NRM. The elevation of nociceptive threshold produced by microinjection of morphine into NRM was reduced by simultaneous microinjection of cinanserin into NRM. Cinanserin alone had no effect when microinjected into NRM. These findings suggest that inhibition of the re-uptake of 5-HT in NRM can elevate nociceptive thresholds and that there may be an interaction between the effects of morphine and 5-HT in NRM.     

The identification of serotonergic neurons in the nucleus raphe magnus by conduction velocity

Histochemical studies have described serotonergic neurons in the nucleus raphe magnus, and since their axons are small, they would be expected to have low conduction velocities. However, previous studies have reported few slow-conducting units in the nucleus. In these studies, raphe-spinal neurons, detected by antidromic activation, were found to exhibit a wide range of conduction velocities, including numbers of slow-conducting units. In a second set of experiments, the number of raphe-spinal units found in control rats and those treated with 5,7-dihydroxytryptamine, a serotonin neurotoxin, were compared. Two groups of slow-conducting units were reduced in treated animals and those units, conducting between 0.7–1.0 m/sec and 3.1–6.0 m/sec, were presumed to be serotonergic. These neurons comprised about 40% of the total found in the nucleus.