猫红核小细胞部向三叉神经感觉核簇的投射——WGA-HRP顺行追踪法研究

将WGA—HRP溶液注入于猫红核吻侧段,顺行追踪了红核向三叉神经感觉核簇投射的纤维行径及终未分布,发现红核有下行纤维投射于对侧三叉神经感觉核簇各亚核。结合作者等既往的研究肯定此投射的起源为对侧红核吻侧2/3段小细胞部背外侧的中、小型细胞群。投射终末以尾侧亚核的深层相当于脊髓背角Ⅳ、Ⅴ、Ⅵ层的地区最为密集,特别是V层最为集中。鉴于此区又是三叉神经初级传入纤维的投射区,还有三叉神经二级感觉(特别是痛觉)神经元胞体及树突的存在,因而作者等认为此区应属于尾侧亚核的一个部分,而不应将之归属于网状结构。红核向此区的投射可能和三叉初级传入纤维之间或两者与二级感觉神经元之间有汇聚的关系。这种汇聚可能对口面部的感觉特别是痛觉的传递产生某种调节作用。     

髋膝关节置换后假体周围感染的治疗

背景：假体周围感染是关节置换后医生及患者最不愿意遇到的并发症之一，其顽固性和难治性一直是让关节科医生头痛的难题。目的：综述国内外近年临床最新治疗髋、膝关节置换后假体周围感染的常用临床治疗手段，包括抗生素治疗、手术治疗、生物治疗、中医药治疗等，以期促进国内治疗假体周围感染的研究进展。方法：第一作者检索中国知网(CNKI)、万方、维普、PubMed等数据库2000年1月至2022年10月的文献，通过阅读题目初筛获得762篇文献，然后通过阅读摘要，排除内容重复、数据可靠性低、观点过时的文献后获得194篇文献，再通过精读原文最终纳入88篇文献。结果与结论：(1)治疗假体周围感染过程中，组合型抗生素给药方案或有助于根除感染；(2)Ⅱ期翻修术仍是治疗假体周围感染的金指标；(3)Ⅰ期翻修术缺乏大样本的临床研究，需要更多的临床观察；(4)生物治疗中的噬菌体疗法、新式载药系统已少量应用于临床，在假体周围感染的预防和根除上表现出其优势特点；(5)中医药配合抗生素、手术治疗手段能提高预防、治疗假体周围感染的效果，但缺乏高等级的循证医学证据。     

基于3D Shepp-Logan头部模型的三维医学图像重建仿真

Shepp-Logan头部模型是计算机断层图像重建(CT)领域仿真计算普遍采用的经典模型。我们提出一种新思路—以3D Shepp-Logan头部模型作为三维医学图像重建领域进行仿真实验和算法性能评测的基本参考模型。首先介绍了3D Shepp-Logan头部模型的设计与实现以及仿真投影数据的计算,进而描述了所设计的三维医学图像重建仿真计算过程。数值实验部分给出了基于3D Shepp-Logan头部模型的三维医学图像重建仿真实验。实验结果表明了新思路的可行性和模型计算的准确性。     

外周伤害性痛刺激对大鼠背海马神经元的影响

为了探讨海马在痛觉调控中的作用，本文应用FOS免疫组化技术结合镇痛药物分析了大鼠对化学性痛刺激的反应。结果表明：将5％福尔马林（100μl）向左前爪掌心皮下注射1h后，双侧海马出现大量的FOS免疫反应阳性神经元；吗啡（5．0mg／kg）预处理10min后再进行福尔马林注射，大鼠双侧背海马内的FOS免疫反应阳性神经元数量显著减少；吗啡（10．0mg／kg）预处理组大鼠，其背海马内的FOS免疫反应阳性神经元数量进一步减少；而纳洛酮在一定程度上具有翻转吗啡的作用。结果提示，海马参与了痛觉调控机制，特别是痛觉情绪的调控机制。     

电刺激尾核头部对丘脑后核痛相关神经元电活动的影响

在61只大鼠的丘脑后核(PO)记录到了516个神经元,其中44.19％是痛相关神经元。它们的痛反应能被吗排类物药所抑制。电刺激尾核头部对痛相关神经元主要产生抑制作用。本文就以上结果在痛觉生理和镇痛中的意义进行了讨论。     

利用医学文献信息资源的途径

医学科研工作者在从事一项课题研究之前 ,首先要对国内外的文献作系统的检索、收集和阅读 ,以了解和分析相关研究的现状 ,在前人或他人已取得的成果或研究进展的基础上 ,寻求获得科学创新的先进起点。随着计算机、通讯技术的飞速发展 ,人们可通过因特网、联机检索等手段方便地获取信息 ,但对于大多数医学科研人员而言 ,特别是基层医务人员 ,由于某些条件的限制 ,查找医学文献信息的途径首选仍是利用图书馆的各种检索工具及图书馆提供的信息服务去获取 ,而笔者在实际工作中却发现不少读者缺乏查阅医学文献的知识及其检索技能 ,为此本文将介绍…     

背根神经节电压门控钠离子通道与神经性疼痛的研究进展

神经性疼痛属于慢性疼痛,以痛觉过敏为特征,表现为自发性持续或间歇性烧灼痛,同时对疼痛刺激的反应性增高.由于发病机制尚不清楚,一直以来是困扰医学界的难题.背根神经节(DRG)作为痛觉传入的第一级神经元在痛觉的外周机制中起着极为重要的作用,对背根神经节上离子通道的认识,对于阐明神经性疼痛的机制有重要意义.本文结合近年来对背根节上电压门控钠通道的研究进展,对其与神经性疼痛的关系加以综述,望有助于同行了解相关领域的最新研究动态.     

内脏痛的脊髓通路研究进展

脊髓背索不仅是一条非伤害性躯体感觉通路,还参与内脏痛觉信息的上行传递,特别是在内脏出现炎症或肿瘤等病理变化时,其作用尤为明显。突触后背索是实现这一传递过程的主要结构。脊髓侧索也是内脏痛觉信息,尤其是痛觉的“自主情感成分”上行传递的重要途径。内脏痛觉信息在上行传递过程中,接受高位颈髓、延脑、丘脑以及小脑等中枢结构的下行调制。源于延脑腹外侧区的下行易化作用可能通过提高脊髓内脏神经元的敏感性,使内脏痛觉信息的上行传递呈现放大效应。     

精神分裂症DA-5-HT平衡假说的再评价

研究发现,脑内神经元的数字以10~(10)计,从此就不难想象CNS中各类神经元以及各类、各个神经元间相互联系的复杂性,这种复杂性及其相互联系为神经介质的相互作用提供了可靠的背景,这种联系及影响有两种类型:其一,一个神经元可以与多种类型的神经元建立联系,即会聚式联系;其二,完成特定功能的神经核团或通路有多种神经介质的参与,即相随作用形式,这些结果表明,神经介质间存在着相互联系和相互影响。中枢神经介质的异常与精神分裂症的关系倍受关注,而且形成多种假说并应用于临床指导治疗、预后估计、疗效判断等,诸如多巴胺假说指导治疗、去甲肾上腺素(NE)理论作为预后疗效依据、5-HT假说     

基于分级检索策略的医学图像检索方法研究

相似病例对医生的诊断大有益处,快速、准确地从医学图像库中检索出相似病理图像是非常重要的.本文提出了一种结合图像纹理特征和形状特征的基于分级检索策略的医学图像检索新方法.该方法先计算图像的灰度共生矩阵,提取能量等纹理特征量,进行初检索,再通过Canny算子提取图像边缘,用投影法计算外边缘在垂直和水平方向上的投影,对初检索结果按形状特征进行二级检索.实验表明,本文方法有较高的查全率和查准率.     

Acupuncture-evoked responses of subnucleus reticularis dorsalis neurons in the rat medulla.

Recordings were made from neurons in subnucleus reticularis dorsalis of the rat. Two populations of neurons could be distinguished: those with total nociceptive convergence which were driven by activating A delta- and C-fibers from any part of the body and those with partial nociceptive convergence which were driven by activating A delta-fibers from any part of the body or C-fibers from some, mainly contralateral, regions. The effects on subnucleus reticularis dorsalis neurons of manual acupuncture, performed by a traditional Chinese acupuncturist at the "Renzhong", "Sousanli", "Changqiang", and "Zusanli" acupoints and at a non-acupoint next to "Zusanli", were studied. Acupuncture stimulation for 30 s at the acupoints or the non-acupoint strongly excited all the total nociceptive convergence neurons tested; these neurons responded with a discharge of rapid onset which was often followed by after-discharges lasting for approximately 30-60 s. The majority but not all of the partial nociceptive convergence neurons responded to 30 s of acupuncture stimulation at the acupoints or the non-acupoint. This was especially the case when the stimulus was applied to contralateral or midline parts of the body. The potency of acupuncture as a means of activating subnucleus reticularis dorsalis neurons varied significantly with the area of the body being stimulated such that: contralateral greater than midline greater than ipsilateral areas. The levels of induced activity were of similar magnitude to those evoked by noxious mechanical stimuli applied under identical experimental conditions. No differences were found between the capacities to activate subnucleus reticularis dorsalis neurons of the "Zusanli" point and the adjacent non-acupoint, no matter whether these were stimulated ipsi- or contralaterally; this suggests a lack of topographical specificity in the activation of these neurons. Since subnucleus reticularis dorsalis neurons are activated exclusively or preferentially by noxious inputs, it is concluded that the signals elicited by manual acupuncture travel through pathways responsible for the transmission of nociceptive information. Since acupuncture, a manoeuvre which is known to elicit widespread extrasegmental antinociceptive effects, activates subnucleus reticularis dorsalis neurons which, anatomically, send dense projections to the dorsal horn at all levels of the spinal cord, we would suggest that this structure may be involved not only in signalling pain but also in modulating pain by means of spino-reticulo-spinal feed-back mechanisms.     

Thalamic mechanism of pain: shell theory of thalamic nociception

In both cats and Japanese macaques, there are nociceptive specific (NS) and wide dynamic range (WDR) neurons in the shell region of the caudal ventrobasal (VB) complex of the thalamus. This comprises both the nucleus ventralis posteromedialis proper (VPM proper), and the nucleus ventralis posterolateralis (VPL). These two classes of nociceptive neurons are spatially segregated, WDR neurons being located both more anteriorly and in a narrow belt around the VB complex. Both NS and WDR neurons are somatotopically organized. These two classes of nociceptive neurons may constitute a thalamic link in the pain pathway from both the dorsal horn of the spinal cord and its trigeminal homologue, to the primary somatosensory cortex. Visceral sympathetic afferent inputs also project to the VPL part of the shell region of the caudal VB complex, there being viscerosomatic convergence onto both NS and WDR neurons. Visceral and cutaneous pain pathways thus appear to share a common projection locus in the shell region of the caudal VB complex.     

Evidence of a specific spinal pathway for the sense of warmth in humans

While research on human sensory processing shows that warm input is conveyed from the periphery by specific, unmyelinated primary sensory neurons, its pathways in the central nervous system (CNS) remain unclear. To gain physiological information on the spinal pathways that convey warmth or nociceptive sensations, in 15 healthy subjects, we studied the cerebral evoked responses and reaction times in response to laser stimuli selectively exciting Adelta nociceptors or C warmth receptors at different levels along the spine. To minimize the conduction distance along the primary sensory neuron, we directed CO(2)-laser pulses to the skin overlying the vertebral spinous processes. Using brain source analysis of the evoked responses with high-resolution electroencephalography and a realistic model of the head based on individual magnetic resonance imaging scans, we also studied the cortical areas involved in the cerebral processing of warm and nociceptive inputs. The activation of C warmth receptors evoked cerebral potentials with a main positive component peaking at 470-540 ms, i.e., a latency clearly longer than that of the corresponding wave yielded by Adelta nociceptive input (290-320 ms). Spinal neurons activated by the warm input had a slower conduction velocity (2.5 m/s) than the nociceptive spinal neurons (11.9 m/s). Brain source analysis of the cerebral responses evoked by the Adelta input yielded a very strong fit for one single generator in the mid portion of the cingulate gyrus; the warmth-related responses were best explained by three generators, one within the cingulate and two in the right and left opercular-insular cortices. Our results support the existence of slow-conducting second-order neurons specific for the sense of warmth.     

Descending influence from the nucleus locus coeruleus/subcoeruleus on visceral nociceptive transmission in the rat spinal cord

Visceral nociceptive signals are the subject of descending modulation from the locus coeruleus/subcoeruleus (LC/SC). We have recently found dorsal horn neurons whose visceral nociceptive responses are not inhibited by the descending LC/SC system (LC/SC-unaffected neurons) in the rat. The aim of the present study was to estimate a possible role of LC/SC-unaffected neurons for pain processing and pain-related responses. We focused on the fact that nociceptive signals from a visceral organ produce not only visceral pain but also visceromotor reflexes (muscular defense). Different effects of LC/SC stimulation can be expected between visceral pain and visceromotor reflexes. To accomplish our objective, the descending colon was electrically stimulated, and both the evoked discharge (ED) in the ventral posterolateral (VPL) nucleus of the thalamus and the electromyogram (EMG) of the abdominal muscle were simultaneously recorded under halothane anesthesia. The ED recorded from the VPL was completely inhibited with the increase of LC/SC stimulus intensity, while the EMG of the abdominal muscle still remained even after the ED disappeared. This result suggests that the minimum visceromotor reflex responses are maintained by the presence of LC/SC-unaffected neurons, which play the important role of protecting the visceral organs. Considering a role of muscular defense, the presence of the LC/SC-unaffected neurons may be advantageous for the individual under an abnormal pain state, such as inflammation.     

Spinal cord hyperexcitability and its role in pain and hyperalgesia

Sensitization of spinal cord nociceptive neurons is commonly interpreted as the cause for the hypersensitivity that characterizes chronic pain states in humans. However, in spite of much basic research in this area it has not been possible to demonstrate a direct link between the hyperexcitability of spinal cord neurons observed experimentally and the underlying mechanism of a chronic pain state. The word sensitization is also used in the literature with various and different meanings from the qualification of a cellular process of enhanced excitability at synaptic level to the characteristics of a chronic pain syndrome. In this article the various meanings of sensitization are described and the relevance of the hyperexcitability of spinal cord neurons to the generation of clinically relevant pain states is discussed. A proposal is made to restrict the use of the word sensitization to the cellular process of enhanced excitability observed experimentally after repetitive stimulation of nociceptive afferents. Caution is also recommended when associating neuronal sensitization in the spinal cord with the mechanisms of chronic pain conditions.     

蛋白酶激活受体4在内脏高敏感性疼痛调节机制的研究进展

研究发现位于初级感觉神经元的蛋白酶激活受体4(PAR4)是参与外周疼痛和炎症机制的重要调节受体。越来越多的证据显示PAR4活化在内脏高敏感性疼痛的调节中起着重要作用,其机制可能是作用于肥大细胞和感觉神经元TRPV1受体,进而抑制内脏高敏感性疼痛反应,这为内脏痛的治疗提供了新的靶点。本文以肠易激综合征为基础,对PAR4调控肥大细胞和TRPV1介导内脏高敏感机制的研究进展进行了综述。     

Prevention of electrical stimulation-induced increase of c-fos immunoreaction in the caudal trigeminal nucleus by kynurenine combined with probenecid

The systemic administration of nitroglycerine, regarded as a migraine model, was previously observed to result in an increased number of c-fos immunoreactive secondary sensory neurons in the caudal trigeminal nucleus, which forward nociceptive impulses to the thalamus. The present investigation tested the hypothesis of whether kynurenine in combination with systemically administered probenecid protects second-order trigeminal neurons against stimulation arriving via central processes of trigeminal ganglion cells. Electrical stimulation of the trigeminal ganglion, one of the experimental migraine models, is known to induce an increase in the number of c-fos immunoreactive second-order nerve cells projecting to the thalamus. Since the synapses between first- and second-order trigeminal neurons are presumed to be mediated by excitatory amino acids, postsynaptic NMDA receptors should be inhibited by kynurenic acid, an endogenous NMDA receptor antagonist. Kynurenic acid, however, does not cross the blood-brain barrier, and its use as a neuroprotective agent is therefore not feasible. In contrast, kynurenine, from which kynurenic acid is formed on the action of kynurenine aminotransferase, passes the blood-brain barrier without difficulty. After the i.p. injection of kynurenine combined with probenecid it was found that the stimulation-induced increase in the c-fos immunoreactivity of the secondary sensory neurons does not occur.     

The role of calcitonin gene-related peptide on the increase in transient receptor potential vanilloid-1 levels in trigeminal ganglion and trigeminal nucleus caudalis activation of rat

Calcitonin gene-related peptide (CGRP) and transient receptor potential vanilloid-1 (TRPV1) play an important role in the development of pain and migraine pathogenesis. Increase in plasma CGRP levels is associated with delayed migraine-like attacks in migraine patients. Although several lines of evidence have indicated a key role of CGRP in migraine pain, its mechanisms remain unclear. In this study, we aimed to investigate the functional role of CGRP on trigeminal nociceptive pathway by determining the alteration in TRPV1 levels in trigeminal ganglion (TG) and the activation of trigeminal nucleus caudalis (TNC) of rat. Post intravenous injection of CGRP (600 ng/kg) at 60 min significantly increased the levels of TRPV1, CGRP, phosphorylated protein kinase C and phosphorylated cyclic AMP responsive element-binding protein in TG of rats. The number of small and medium TRPV1 and CGRP positive immunostaining neurons accompanying with co-localization of TRPV1 with CGRP neurons were significantly increased in TG of CGRP-injected rats. The sustained increase in c-Fos expression in TNC neurons was also observed in CGRP-injected rats. These results indicate that CGRP may participate in trigeminal nociceptive system sensitization by induced increase in TRPV1 and CGRP levels in TG neurons and activation of the central neurons in TNC.     

Tumor necrosis factor α sensitizes spinal cord TRPV1 receptors to the endogenous agonist N-oleoyldopamine

Modulation of synaptic transmission in the spinal cord dorsal horn is thought to be involved in the development and maintenance of different pathological pain states. The proinflamatory cytokine, tumor necrosis factor α (TNFα), is an established pain modulator in both the peripheral and the central nervous system. Up-regulation of TNFα and its receptors (TNFR) in dorsal root ganglion (DRG) cells and in the spinal cord has been shown to play an important role in neuropathic and inflammatory pain conditions. Transient receptor potential vanilloid 1 (TRPV1) receptors are known as molecular integrators of nociceptive stimuli in the periphery, but their role on the spinal endings of nociceptive DRG neurons is unclear. The endogenous TRPV1 receptor agonist N-oleoyldopamine (OLDA) was shown previously to activate spinal TRPV1 receptors. In our experiments the possible influence of TNFα on presynaptic spinal cord TRPV1 receptor function was investigated. Using the patch-clamp technique, miniature excitatory postsynaptic currents (mEPSCs) were recorded in superficial dorsal horn neurons in acute slices after incubation with 60 nM TNFα. A population of dorsal horn neurons with capsaicin sensitive primary afferent input recorded after the TNFα pretreatment had a basal mEPSC frequency of 1.35 ± 0.20 Hz (n = 13), which was significantly higher when compared to a similar population of neurons in control slices (0.76 ± 0.08 Hz; n = 53; P < 0.01). In control slices application of a low concentration of OLDA (0.2 uM) did not evoke any change in mEPSC frequency. After incubation with TNFα, OLDA (0.2 uM) application to slices induced a significant increase in mEPSC frequency (155.5 ± 17.5%; P < 0.001; n = 10). Our results indicate that TNFα may have a significant impact on nociceptive signaling at the spinal cord level that could be mediated by increased responsiveness of presynaptic TRPV1 receptors to endogenous agonists. This could be of major importance, especially during pathological conditions, when increased levels of TNFα and TNFR are present in the spinal cord.     

Cytotoxic targeting of isolectin IB4-binding sensory neurons.

The isolectin I-B4 (IB4) binds specifically to a subset of small sensory neurons. We used a conjugate of IB4 and the toxin saporin to examine in vivo the contribution of IB4-binding sensory neurons to nociception. A single dose of the conjugate was injected unilaterally into the sciatic nerve of rats. The treatment resulted in a permanent selective loss of IB4-binding neurons as indicated by histological analysis of dorsal root ganglia, spinal cord, and skin from treated animals. Behavioral measurements showed that 7-10 days after the injection, conjugate-treated rats had elevated thermal and mechanical nociceptive thresholds. However, 21 days post-treatment the nociceptive thresholds returned to baseline levels.These results demonstrate the utility of the IB4-saporin conjugate as a tool for selective cytotoxic targeting and provide behavioral evidence for the role of IB4-binding neurons in nociception. The decreased sensitivity to noxious stimuli associated with the loss of IB4-binding neurons indicates that these sensory neurons are essential for the signaling of acute pain. Furthermore, the unexpected recovery of nociceptive thresholds suggests that the loss of IB4-binding neurons triggers changes in the processing of nociceptive information, which may represent a compensatory mechanism for the decreased sensitivity to acute pain.