L－谷氨酸分别兴奋大鼠内外侧缰核引起血压和痛阈变化的关系

本实验探讨分别兴奋缰核不同部位引起血压和痛阈变化的关系。实验分别在戊巴比妥钠和乌拉坦麻醉的大鼠上进行,采用玻璃微电极微量注射的方法,将Ｌ－谷氨酸（Ｌ－Ｇｌｕ）分别注入到大鼠内侧缰核（ＭＨｂ）和外侧缰核（ＬＨｂ）,分别观察痛阈和血压变化。结果显示：ＭＨｂ兴奋可明显提高痛阈和血压,痛阈提高５３％,血压由１３．８７±２．１４升高至１６．２１±２．４２ｋＰａ（Ｐ＜０．００１）。而ＬＨｂ兴奋引起痛阈降低３６％,血压由１４．８±２．０６降低到达１３．０９±１．８２ｋＰａ（Ｐ＜０．００１）。应用同一动物,分别兴奋内侧和外侧经核,同时观察痛阈和血压变化,所得结果和分组实验一致。结果表明兴奋缰核对痛阈和心血管活动的影响具有部位特异性,同时在现出两者之间的密切联系。     

损毁缰对应激性高血压形成的影响

目的和方法：运用核团损毁和微量注射的方法观察损毁缰核（Ｈｂ）对应激性高血压（ＳＩＨ）形成进程的影响及ＳＩＨ大鼠Ｈｂ内神经元对Ｌ－谷氨酸反应性的变化。结果：（１）损毁双侧Ｈｂ延缓了ＳＩＨ的形成进程;（２）在ＳＩＨ大鼠内侧Ｈｂ（ＭＨｂ）微量注射不同浓度的ＣＩｕ,血压明显升高;呈浓度依赖性,升高值与正常大鼠ＭＨｂ注入等量Ｇｌｕ引起的升高值相比,有显著性差异;（３）在ＳＩＨ大鼠外侧Ｈｂ（ＬＨｂ）注入不同浓     

侧脑室注射血管紧张素Ⅱ对大鼠血压和缰核内神经元电活动的影响

实验观察了侧脑室注射（ｉｃｖ）及缰核（ｈａｂｅｎｕｌａ ｎｕｃｌｅｕｓ）内微电泳血管紧张素Ⅱ（ＡⅡ）与「Ｓａｒ＾１,Ｔｈｒ＾３」－ＡⅡ（ＳＴ－ＡⅡ,ＡⅡ拮抗剂）对正常和诮激性高血压（ｓｔｒｅｓｓ－ｉｎｄｕｃｅｄ ｈｙｐｅｒｔｅｎｓｉｏｎ ＳＩＨ）大鼠血压及内外侧缰核（ＭＨｂ、ＬＨｂ）内心血管神经元入电活动的影响。结果如下：ｉｃｖ ＡⅡ或ＳＴ－ＡⅡ,正常鼠和ＳＩＨ大鼠血压均升高或降低,ＳＩＨ鼠较正常     

缰核参与应激性高血压的形成及其机制研究

电击大鼠足底形成应激性高血压（ＳＩＨ）,研究了缰核（Ｈｂ）在其中的作用机制。损毁Ｈｂ可降低ＳＩＨ升高的幅度。ＳＩＨ鼠内外侧Ｈｂ（ＭＨｂ,ＬＨｂ）对谷氨酸（Ｇｌｕ）的敏感性高于正常鼠。足底电击使血浆和Ｈｂ内血管紧张素Ⅱ（ＡｎｇⅡ）明显升高,侧脑室和ＭＨｂ分别注射ＡｎｇⅡ或ｓａｒａｌａｓｉｎ,在ＳＩＨ鼠引起明显的血压变化。微电泳ＡｎｇⅡ,ｓａｒａｌａｓｉｎ可分别明显改变ＳＩＨ鼠Ｈｂ内神经元的放电活动。     

大鼠脚内核的镇痛作用

本实验应用核团内微量注射L谷氨酸,利多卡因,bieuculline,GABA以及用辐射热甩尾法测痛等手段观察脚内核的镇痛作用,向双侧脚内核注射25 100nmol的L谷氨酸可引起大鼠痛阈升高,这个作用可为缰核内注射2 利多卡因0.5mol或0.2 bieuculline0.5mol所阻断,反之,向缰核内注射200nmolGABA可引起大鼠痛阈升高,上述实验表明,参与痛觉调制,脚内核缰核的GABA能纤维参与了脚内核的痛觉调制活动。     

电刺激内脏大神经对外侧缰核单位放电的影响

外侧缰核(LHN)内存在着对躯体伤害性刺激放电增多的痛兴奋神经元(LHPE)和放电减少的痛抑制神经元(LHPI)。刺激或损毁缰核可以分别引起动物痛阈的降低或升高,并且影响针刺镇痛的效应。缰核与内脏痛之间的关系目前则了解甚少。本实验主要探讨LHN能否接受和整合内脏伤害性传入冲动以及这种冲动到达LHN的可能途径。     

大鼠下丘脑-缰核系统对中缝大核痛反应神经元放电的影响

在大鼠尾部给以伤害性刺激后,外侧缰核和中缝大核的单位按其反应型式可分为四种类型,即痛兴奋单位、广动力型单位、痛抑制单位和无反应单位。电刺激下丘脑外侧区对外侧缰核中各种单位的自发放电主要产生抑制作用,对其中痛兴奋单位和痛抑制单位的自发放电尤为明显。刺激下丘脑外侧区对中缝大核中痛兴奋单位的自发放电有明显兴奋作用,刺激外侧缰核则有抑制作用,损毁外侧缰核后,下丘脑外侧区的兴奋作用消失。分别刺激下丘脑外侧区和外侧缰核对中缝大核中痛抑制单位的自发放电都有明显的抑制作用;损毁外侧缰核后下丘脑外侧区的抑制作用仍存在。以上结果提示,下丘脑外侧区影响中缝大核活动的途径有二。其一可能是通过去除外侧缰核对中缝大核中痛兴奋单位的紧张性抑制作用;另外还可能通过外侧缰核以外的途径抑制中缝大核中痛抑制单位的活动。     

缰核痛相关神经元对伤害性刺激和吗啡的反应

目的:观察缰核痛相关神经元对经典镇痛药吗啡的反应,了解缰核的痛觉属性.方法:实验在浅麻醉下的成年大鼠进行.通过脑室插管微量注射,或经五管微电极电泳吗啡、纳络酮、八肽胆囊收缩素(CCK-8)等,并记录缰核内痛相关神经元的单位放电.结果:在内侧缰核、外侧缰核记录的痛相关神经元放电,又可分为痛兴奋性神经元和痛抑制性神经元.在缰核微电泳吗啡后,痛兴奋性神经元以抑制反应为主,痛抑制性神经元以兴奋反应为主.微电泳纳洛酮可以翻转吗啡对缰核的作用.在吗啡耐受大鼠腹腔注射吗啡10 mg/kg,LHb痛相关神经元表现为镇痛效应的数量远大于MHb痛相关神经元的,表明外侧缰核受吗啡的作用程度高于内侧缰核.对吗啡耐受大鼠脑室注入CCK拮抗剂后,再由腹腔注射吗啡,可减弱对吗啡的耐受程度.反之,在腹腔注射吗啡(10 mg/kg)10 min后,侧脑室注射CCK-8(15 ng/10μl),CCK-8可拮抗吗啡对LHb的镇痛作用,但对MHb的拮抗作用不明显.结论:缰核的痛兴奋性神经元和痛抑制性神经元对伤害性(痛)刺激敏感而不易发生适应.其中外侧缰核神经元对吗啡的敏感性高于内侧缰核神经元.     

损毁和刺激垂体对大鼠痛阈的影响

采用局限性损毁和刺激垂体的方法,以行为测痛为指标,观察大鼠垂体在痛觉调节中的作用以及地塞米松（Ｄｅｘ）对其影响。实验结果显示,损毁垂体中间叶（ＩＬ）及邻近的前叶（ＡＬ）,大鼠痛阈明显低于手术前的痛阈（Ｐ＜０．０１）。电刺激垂体的上述同样部位,大鼠痛阈明显高于手术基础值及自身假刺激值（Ｐ＜０．００１）。经Ｄｅｘ处理的动物,电刺激垂体不再引起痛阈升高。结果表明,大鼠垂体ＩＬ及靠近ＡＬ与痛调节有关,这种     

阻断缰核或内侧前脑束对 L-谷氨酸刺激隔区引起的镇痛作用的影响

以辐射热-甩尾潜伏期作为测定大鼠痛阈的指标,用向隔区内微量注射 L-谷氨酸和向缰核或内侧前脑束微量注射利多卡因,可逆性刺激和阻断上述核团。L-谷氨酸刺激隔区使大鼠痛阈明显提高,并且在13.6—100nmol 呈现剂量-效应关系。利多卡因阻断缰核,使隔区的镇痛作用明显减弱(P<0.001)。而阻断内侧前脑束对隔区的镇痛作用无明显影响(P>0.05)。结果表明隔区在脊髓水平抑制痛觉信息的传导主要是下行通过缰核实现的。     

Ultrastructural features and acetylcholinesterase histochemistry of the rat habenular complex

The ultrastructural features and the acetylcholinesterase (AChE) localization of the rat habenula have been studied. On the basis of different morphology and AChE content, it is suggested that at least two types of neurons are present in the medial habenula (MHb) and three types of neurons in the lateral habenula (LHb). In particular, actively AChE-synthesizing neurons have been noticed in both LHb and MHb. Some unusual ultrastructural arrangements of the endoplasmic reticulum have been described in habenular neurons. Finally, the most common types of synaptic contacts present in the habenular complex have been surveyed.     

芦沙坦的降压效应和内、外侧缰核神经元单位放电的关系

目的和方法 :观察腹腔注射 (i.p) 2mg kg和 10mg kg芦沙坦 (losartan)对大鼠股动脉血压 (aterialbloodpressure ,AP)和心率 (heartrate,HR)的影响以及与缰核 (Hb)神经元活动的关系。用玻璃微电极记录内侧缰核 (MHb)、外侧缰核(LHb)神经元单位放电活动 ,观察 10mg kg芦沙坦对其放电频率的影响。结果 :2mg kg芦沙坦对大鼠AP和HR无明显影响 ;(10mg kg芦沙坦可显著降低大鼠动脉血压 ,但对心率无明显影响。 10mg kg芦沙坦可使LHb内 6 6 6 6 % 12 18)神经元单位放电频率增加 ,使MHb内 6 1 90 % (13 2 1)神经元单位放电频率减少。结论 :10mg kg芦沙坦可明显地降低大鼠AP ,但 2mg kg芦沙坦对AP无明显影响 ;10mg kg芦沙坦可兴奋LHb和抑制MHb,产生降压效应     

Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process.     

褪黑色素对缰核痛神经元单位放电的影响及可能机制

目的通过观察褪黑色素对缰核痛神经元单位放电的影响,进一步证明褪黑色素的中枢镇痛作用及可能机制。方法：应用细胞外神经元单位放电记录方法,记录缰核神经元痛相关神经元放电,并观察外侧缰核痛神经元在褪黑色素作用下电活动的改变,及对伤害性刺激痛敏感性的改变,在此基础上观察纳洛酮的翻转作用。结果：褪黑色素影响外侧缰核痛神经元的电活动,并使外侧缰核痛神经元对伤害性刺激敏感性降低,此种作用可被纳洛酮翻转。结论：褪黑色素可通过作用于外侧缰核的阿片受体而影响其痛相关神经元对痛刺激的反应,这可能是褪黑色素中枢镇痛机制之一。     

Electrical stimulation of the primate lateral habenula suppresses saccadic eye movement through a learning mechanism

The lateral habenula (LHb) is a brain structure which represents negative motivational value. Neurons in the LHb are excited by unpleasant events such as reward omission and aversive stimuli, and transmit these signals to midbrain dopamine neurons which are involved in learning and motivation. However, it remains unclear whether these phasic changes in LHb neuronal activity actually influence animal behavior. To answer this question, we artificially activated the LHb by electrical stimulation while monkeys were performing a visually guided saccade task. In one block of trials, saccades to one fixed direction (e.g., right direction) were followed by electrical stimulation of the LHb while saccades to the other direction (e.g., left direction) were not. The direction-stimulation contingency was reversed in the next block. We found that the post-saccadic stimulation of the LHb increased the latencies of saccades in subsequent trials. Notably, the increase of the latency occurred gradually as the saccade was repeatedly followed by the stimulation, suggesting that the effect of the post-saccadic stimulation was accumulated across trials. LHb stimulation starting before saccades, on the other hand, had no effect on saccade latency. Together with previous studies showing LHb activation by reward omission and aversive stimuli, the present stimulation experiment suggests that LHb activity contributes to learning to suppress actions which lead to unpleasant events.     

How changing the inversion/eversion foot angle affects the nondriving intersegmental knee moments and the relative activation of the vastii muscles in cycling

Nondriving intersegmental knee moment components (i.e., varus/valgus and internal/external axial moments) are thought to be primarily responsible for the etiology of overuse knee injuries such as patellofermoral pain syndrome in cycling because of their relationship to muscular imbalances. However the relationship between these moments and muscle activity has not been studied. Thus the four primary objectives of this study were to test whether manipulating the inversion/eversion foot angle alters the varus/valgus knee moment (Objective 1) and axial knee moment (Objective 2) and to determine whether activation patterns of the vastus medialis oblique (VMO), vastus lateralis (VL), and tensor fascia latae (TFL) were affected by changes in the varus/valgus (Objective 3) and axial knee moments (Objective 4). To fulfill these objectives, pedal loads and lower limb kinematic data were collected from 15 subjects who pedaled with five randomly assigned inversion/eversion angles: 10 deg and 5 deg everted and inverted and 0 deg (neutral). A previously described mathematical model was used to compute the nondriving intersegmental knee moments throughout the crank cycle. The excitations of the VMO, VL, and TFL muscles were measured with surface electromyography and the muscle activations were computed. On average, the 10-deg everted position decreased the peak varus moment by 55% and decreased the peak internal axial moment by 53% during the power stroke (crank cycle region where the knee moment is extensor). A correlation analysis revealed that the VMO/VL activation ratio increased significantly and the TFL activation decreased significantly as the varus moment decreased. For both the VMO/VL activation ratio and the TFL activation, a path analysis indicated that the varus/valgus moment was highly correlated to the axial moment but that the correlation between muscle activation and the varus moment was due primarily to the varus/valgus knee moment rather than the axial knee moment. The conclusion from these results is that everting the foot may be beneficial towards either preventing or ameliorating patellofemoral pain syndrome in cycling.     

Different hip rotations influence hip abductor muscles activity during isometric side-lying hip abduction in subjects with gluteus medius weakness

The purpose of this study was to establish the effects of different hip rotations during isometric side-lying hip abduction (SHA) in subjects with gluteus medius (Gmed) weakness by investigating the electromyographic (EMG) amplitude of the Gmed, tensor fasciae latae (TFL) activity, and gluteus maximus (Gmax), and the activity ratio of the Gmed/TFL, Gmax/TFL, and Gmed/Gmax. Nineteen subjects with Gmed weakness were recruited for this study. Subjects performed three isometric hip abductions: frontal SHA with neutral hips (SHA-N), frontal SHA with hip medial rotation (SHA-MR), and frontal SHA with hip lateral rotation (SHA-LR). Surface EMG amplitude was measured to collect the EMG data from the Gmed, TFL, and Gmax. A one-way repeated-measures analysis of variance was used to determine the statistical significance of the Gmed, TFL, and Gmax EMG activity and the Gmed/TFL, Gmax/TFL, and Gmed/Gmax EMG activity ratios. Gmed EMG activity was significantly greater in SHA-MR than in SHA-N. TFL EMG activity was significantly greater in SHA-LR than in SHA-N. The Gmed/TFL and Gmed/Gmax EMG activity ratios were also significantly greater in SHA-MR than in SHA-N or SHA-LR. The results of this study suggest that SHA-MR can be used as an effective method to increase Gmed activation and to decrease TFL activity during SHA exercises.     

Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin

The lateral habenula (LHb) has recently been identified as a key regulator of the reward system by driving inhibition onto dopaminergic neurons. However, the nature and potential modulation of the major input to the LHb originating from the basal ganglia are poorly understood. Although the output of the basal ganglia is thought to be primarily inhibitory, here we show that transmission from the basal ganglia to the LHb is excitatory, glutamatergic, and suppressed by serotonin. Behaviorally, activation of this pathway is aversive, consistent with its role as an "antireward" signal. Our demonstration of an excitatory projection from the basal ganglia to the LHb explains how LHb-projecting basal ganglia neurons can have similar encoding properties as LHb neurons themselves. Our results also provide a link between antireward excitatory synapses and serotonin,?a neuromodulator implicated in depression.     

Electrical Stimulation of Lateral Habenula during Learning: Frequency-Dependent Effects on Acquisition but Not Retrieval of a Two-Way Active Avoidance Response

The lateral habenula (LHb) is an epithalamic structure involved in signaling reward omission and aversive stimuli, and it inhibits dopaminergic neurons during motivated behavior. Less is known about LHb involvement in the acquisition and retrieval of avoidance learning. Our previous studies indicated that brief electrical stimulation of the LHb, time-locked to the avoidance of aversive footshock (presumably during the positive affective “relief” state that occurs when an aversive outcome is averted), inhibited the acquisition of avoidance learning. In the present study, we used the same paradigm to investigate different frequencies of LHb stimulation. The effect of 20 Hz vs. 50 Hz vs. 100 Hz stimulation was investigated during two phases, either during acquisition or retrieval in Mongolian gerbils. The results indicated that 50 Hz, but not 20 Hz, was sufficient to produce a long-term impairment in avoidance learning, and was somewhat more effective than 100 Hz in this regard. None of the stimulation parameters led to any effects on retrieval of avoidance learning, nor did they affect general motor activity. This suggests that, at frequencies in excess of the observed tonic firing rates of LHb neurons (>1–20 Hz), LHb stimulation may serve to interrupt the consolidation of new avoidance memories. However, these stimulation parameters are not capable of modifying avoidance memories that have already undergone extensive consolidation.