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Neuroscience Bulletin 2011年第5期27卷 343-350页

作者：陈军第四军医大学疼痛生物医学研究所西安710038 首都医科大学疼痛生物医学研究所北京100069

The concept of pain has remained a topic of long debate since its emergence in ancient times. The initial ideas of pain were formulated in both the East and the West before 1800. Since 1800, due to the development of experimental sciences, different theories of pain have emerged and become central topics of debate. However, the existing theories of pain may be appropriate for the interpretation of some aspects of pain, but are not yet comprehensive. The history of pain problems is as long as that of human beings;however, the understanding of pain mechanisms is still far from sufficient. Thus, intensive research is required. This historical review mainly focuses on the development of pain theories and the fundamental discoveries in this field. Other historical events associated with pain therapies and remedies are beyond the scope of this review.

关键词： pain theory history

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Roles of the hippocampal formation in pain information processing

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Neuroscience Bulletin 2009年第5期25卷 237-266页

作者：刘明刚陈军首都医科大学疼痛生物医学研究所北京100069 第四军医大学附属唐都医院疼痛生物医学研究所西安710038

Pain is a complex experience consisting of sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Now it has been gradually known that noxious information is processed by a widely-distributed, hierarchically- interconnected neural network, referred to as neuromatrix, in the brain. Thus, identifying the multiple neural networks subserving these functional aspects and harnessing this knowledge to manipulate the pain response in new and beneficial ways are challenging tasks. Albeit with elaborate research efforts on the cortical responses to painful stimuli or clinical pain, involvement of the hippocampal formation （HF） in pain is still a matter of controversy. Here, we integrate previous animal and human studies from the viewpoint of HF and pain, sequentially representing anatomical, behavioral, electrophysiological, molecular/ biochemical and functional imaging evidence supporting the role of HF in pain processing. At last, we further expound on the relationship between pain and memory and present some unresolved issues.

关键词： pain hippocampal formation anatomy behavior electrophysiology functional imaging

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Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices:Multi-electrode array recordings

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Neuroscience Bulletin 2009年第5期25卷 309-318页

作者：何莹刘明刚巩克瑞陈军首都医科大学疼痛生物医学研究所北京100069 第四军医大学附属唐都医院疼痛生物医学研究所西安710038

Objective There is substantial evidence supporting the notion that the anterior cingulate cortex （ACC） is an important limbic structure involved in multiple brain functions such as sensory perception, motor conflict monitoring, memory, emotion and cognition. It has been shown that long term potentiation （LTP） is an important synaptic model of neural plasticity in the ACC, however, little is known about the spatiotemporal properties of ACC at network level. The present study was designed to see the LTP induction effects across different layers of the ACC by using different conditioning stimuli （CS） protocols. Methods A unique multi-electrode array recording technique was used in the acutely-dissociated ACC slices of rats. Long and short train theta burst stimulation （TBS） paradigms were applied in layer V-VI as the CS and the LTP induction effects were compared across different layers of the ACC. Briefly, both long and short train TBS are composed of bursts （4 pulses at 100 Hz） with a 200 ms interval, however, the former （TBS1） was with 10 trains and the latter （TBS2） was with 5 trains. After test stimulation at layer V-VI in the ACC, network field potentials （FPs） could be simultaneously recorded across all layers of the ACC. Results The waveforms of FPs were different across different layers. Namely, positive-going waveforms were recorded in layer I and negative-going waveforms were recorded in layers V-VI, in contrast, complex waveforms were localized mainly in layers II-III. Following application of two CS protocols, the induction rate of LTP was significantly different between TBS 1 and TBS2 regardless of the spatial properties. TBS1 had more than 60% success, while TBS2 was less than 25% in induction of LTP. Moreover, both the 2 CS protocols could induce LTP in layers II-III and layers V-VI without layer-related difference. However, no LTP was inducible in layer I. Conclusion The present findings indicate that stimulation protocols may, at least in part, accoun

关键词： long term potentiation anterior cingulate cortex theta burst stimulation multi-electrode array recordings rat

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Effects of SKF-96365, a TRPC inhibitor, on melittin-induced inward current and intracellular Ca^2+ rise in primary sensory cells

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Neuroscience Bulletin 2011年第3期27卷 135-142页

作者：丁静肖勇吕丹杜意如崔秀玉陈军首都医科大学疼痛生物医学研究所北京100069 第四军医大学唐都医院疼痛生物医学研究所西安710038

Objective Melittin （MEL） is a major component of bee venom and can produce both persistent spontaneous nociception and pain hypersensitivity when injected subcutaneously in the periphery. The present study aimed to examine the roles of transient receptor potential canonical （TRPC） channels in mediation of MEL-indueed activation of primary nociceptive cells. Methods Whole-cell patch-clamp and laser scanning confocal calcium detection were used to evalu- ate the effects of SKF-96365, a TRPC inhibitor, applied on the acutely isolated dorsal root ganglion （DRG） cells of rat, on MEL-induced increase in intracellular calcium concentration （[Ca2＋]i） and inward current. Results Under voltage- clamp mode, 43.9% （40/91） DRG cells were evoked to give rise to the inward current by 2 pmol/L MEL, which could be significantly suppressed by 3 doses of SKF-96365 （1, 5 and 10μmol/L） in a dose-dependent manner. Of the other 210 cells, 67.6% responded to MEL with an intracellular Ca2＋ rise, as revealed by confocal calcium imaging. Of these MEL- sensitive cells, 46.5% （66/142） were suppressed by the highest dose of SKF-96365. Conclusion MEL-induced activation of small to medium-sized DRG cells can be suppressed by SKF-96365, suggesting the involvement of TRPC channels in the mediation of MEL-induced activation of primary nociceptive cells.

关键词： melittin transient receptor potential canonical channel dorsal root ganglion patch-clamp technique calciumimaging

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共情神经科学:探索亲社会行为、利他主义和道德的生物学基础

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学习与探索 2019年第7期 139-147页

作者：陈军第四军医大学唐都医院疼痛生物医学研究所

传统上共情被认为是人类独有的能力,所以长期以来该领域一直由"共情人类中心论"所统治。结合近十年来动物共情研究的突破性进展和共情词源与定义的演化,本文成功地梳理出一条新的"共情生物进化"时空发展线索,并用... 详细信息

传统上共情被认为是人类独有的能力,所以长期以来该领域一直由"共情人类中心论"所统治。结合近十年来动物共情研究的突破性进展和共情词源与定义的演化,本文成功地梳理出一条新的"共情生物进化"时空发展线索,并用生物进化的观点重新定义了共情;沿着道德哲学、社会学、生物学和神经科学的发展轨迹,论证了共情是亲社会行为、利他主义和道德的生物学基础;提出在"生物-社会心理-脑-行为"的范式下,结合现代神经科学技术去开展共情研究,为共情神经科学的发展开拓了美好前景。

关键词：共情亲社会行为利他主义道德神经科学

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Neural circuits and temporal plasticity in hindlimb representation of rat primary somatosensory cortex:revisited by multi-electrode array on brain slices

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Neuroscience Bulletin 2010年第3期26卷 175-187页

作者：王丹丹李震常颖王蕊蕊陈雪峰赵振宇曹发乐金建慧刘明刚陈军首都医科大学疼痛生物医学研究所北京100069 第四军医大学唐都医院疼痛生物医学研究所暨功能性脑疾病研究所西安710038

Objective The well-established planar multi-electrode array recording technique was used to investigate neural circuits and temporal plasticity in the hindlimb representation of the rat primary somatosensory cortex （S1 area） . Methods Freshly dissociated acute brain slices of rats were subject to constant perfusion with oxygenated artificial cerebrospinal fluid （95% O2 and 5% CO2） , and were mounted on a Med64 probe （64 electrodes, 8×8 array） for simultaneous multi-site electrophysiological recordings. Current sources and sinks across all the 64 electrodes were transformed into two-dimensional current source density images by bilinear interpolation at each point of the 64 electrodes. Results The local intracortical connection, which is involved in mediation of downward information flow across layers II-VI, was identified by electrical stimulation （ES） at layers II-III. The thalamocortical connection, which is mainly involved in mediation of upward information flow across layers II-IV, was also characterized by ES at layer IV. The thalamocortical afferent projections were likely to make more synaptic contacts with S1 neurons than the intracortical connections did. Moreover, the S1 area was shown to be more easily activated and more intensively innervated by the thalamocortical afferent projections than by the intracortical connections. Finally, bursting conditioning stimulus （CS） applied within layer IV of the S1 area could success-fully induce long-term potentiation （LTP） in 5 of the 6 slices （83.3%） , while the same CS application at layers II-III induced no LTP in any of the 6 tested slices. Conclusion The rat hindlimb representation of S1 area is likely to have at least 2 patterns of neural circuits on brain slices： one is the intracortical circuit （ICC） formed by interlaminar connections from layers II-III, and the other is the thalamocortical circuit （TCC） mediated by afferent connections from layer IV. Besides, ICC of the S1 area is spatially limited, with les

关键词： planar multi-electrode array two-dimensional current source density imaging primary somatosensory cortex neural circuits long-term potentiation

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5-HT2C受体亚型参与易化大鼠内嗅区-海马通路的突触传递:平面微电极阵列记录技术研究

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生理学报 2012年第3期64卷 259-268页

作者：许燕金建慧王燕王蕊蕊李震陈军首都医科大学疼痛生物医学研究所北京100069 第四军医大学唐都医院疼痛生物医学研究所暨功能性脑疾病研究所西安710038

本实验旨在运用64通道(8 × 8)平面微电极阵列记录技术(MED-64系统)探讨5-HT2C受体在调节内嗅区-海马突触传递和突触联系中的作用。将急性分离的大鼠海马脑片置于MED-64系统的电极平皿中,持续灌流通入95% O2和5% CO2混合气的人工脑... 详细信息

本实验旨在运用64通道(8 × 8)平面微电极阵列记录技术(MED-64系统)探讨5-HT2C受体在调节内嗅区-海马突触传递和突触联系中的作用。将急性分离的大鼠海马脑片置于MED-64系统的电极平皿中,持续灌流通入95% O2和5% CO2混合气的人工脑脊液,孵育2 h后进行多电极阵列同步记录。选一个电极进行电刺激(刺激强度30～199 μA,正负双波脉冲,单波宽0.1 ms,频率0.1 Hz),其余63个电极作为记录电极。最佳有效刺激部位恰好位于前穿质通路(perforant path, PP)上,电刺激结果可以分别在海马CA1区和齿状回(dentate gyrus, DG)记录到兴奋性突触后场电位(field excitatory post-synaptic potential,fEPSP)。我们以往研究结果已显示内嗅区-CA1和内嗅区-DG直接突触联系是由谷氨酸非NMDA受体所介导的兴奋通路。在稳定地诱导出网络fEPSP后,分别给予5-HT2C受体激动剂DOI和选择性拮抗剂SB242084,观察与计算fEPSP的反应幅值与斜率变化。同时利用双线性内插法计算出64个点的电流源(current source)与电流井(current sink),并将其转换为二维电流源密度(two-dimensional current source density, 2D-CSD)分布图。结果显示,结合fEPSP波的极相与2D-CSD成像,可见电刺激PP纤维在CA1区(腔隙分子层、锥体细胞层)和上部DG的分子层均发生突触兴奋引起的去极化,fEPSP为负向波,在空间上形成2D-CSD成像的电流井(蓝色区域)。同时,可在DG的颗粒细胞层和门部检测出正向波,形成2D-CSD成像的电流源(黄色区域),这反映了颗粒细胞在树突部位发生去极化后很快沿门向CA3传播电信号。在此基础上,给予5-HT2C受体激动剂DOI后,海马内有效突触联系(>基线20%的fEPSP)的空间网络范围显著扩大,突触传递效能显著增强。而相对应的是,给予5-HT2C受体的选择性拮抗剂SB242084,则海马内有效突触联系空间网络范围显著缩小,突触反应强度减弱。以上结果提示,内源性5-HT作用于5-HT2C受体可易化内嗅区-海马突触传递效能,扩大有效突触联系,引起突触反应的兴奋作用。

关键词： 5-TH2C受体内嗅区-海马通路突触传递平面微电极阵列记录技术大鼠

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TRPV1介导甲醛激活初级传入伤害性感受器细胞的作用(英文)

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生理学报 2009年第5期61卷 404-416页

作者：田丽娟杜意如萧勇吕卓敏于耀清崔秀玉陈军首都医科大学疼痛生物医学研究所北京100069 第四军医大学唐都医院疼痛生物医学研究所暨功能性脑疾病研究所西安710038

福尔马林致痛模型是化学伤害性刺激引起急性和持续性痛常用的动物模型。本研究旨在细胞和整体水平上证明TRPV1受体是否参与甲醛溶液(甲醛是福尔马林溶液的主要成分)对初级伤害性感受器细胞的激活过程。运用电流钳记录的92个背根神经节... 详细信息

福尔马林致痛模型是化学伤害性刺激引起急性和持续性痛常用的动物模型。本研究旨在细胞和整体水平上证明TRPV1受体是否参与甲醛溶液(甲醛是福尔马林溶液的主要成分)对初级伤害性感受器细胞的激活过程。运用电流钳记录的92个背根神经节细胞中,大约有34%的中、小细胞对甲醛溶液敏感,产生动作电位的发放,其产生动作电位的潜伏期是(367.34±32.96)s,并且单个动作电位复极化相具有伤害性感受器细胞的特征性,如动作电位间期较长、复极化相有"驼峰"以及较长的后超极化相。在同时给予TRPV1受体抑制剂Capsazepine(CPZ)时,甲醛溶液诱发背根神经节细胞产生的放电可以被阻断,但对细胞膜去极化不能完全阻断。在激光共聚焦钙成像中记录的160个背根神经节细胞中,有32%的细胞对甲醛溶液敏感,可以产生胞内钙离子浓度的升高,同时加入CPZ后,67%的这些甲醛敏感性细胞的胞内钙浓度升高可以被抑制。在电压钳状态下,甲醛溶液可以诱发背根神经节细胞产生内向电流,大约有41%的细胞对甲醛溶液敏感,实验证明甲醛溶液诱发产生内向电流的幅度呈剂量依赖。当同时给予CPZ时比TRPA1受体选择性抑制剂HC-030031抑制内向电流的幅度明显。利用行为学技术方法证明足底注射CPZ可以明显抑制福尔马林溶液所致的第一相全程和第二相内仅第25～55min的自发缩足反射。以上结果提示,甲醛溶液选择性地激活一个亚群的初级传入伤害性感受器细胞,甲醛激活的动作电位的发放主要参与福尔马林诱发的第一相伤害性感受的产生。本实验进一步证明甲醛激活初级伤害性感受器细胞可能是通过TRPV1受体和/或TRPA1受体参与介导的。

关键词：福尔马林试验伤害性感受 TRPV1受体背根神经节膜片钳钙成像

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大黄蒽醌衍生物对大鼠结肠及LoVo细胞水通道蛋白4表达的调节效应

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中国中西医结合杂志 2008年第9期28卷 818-823页

作者：张文生李锋鲍军强王胜春尚刚伟李军昌王长海第四军医大学西京医院中医科暨全军中医内科专科中心西安710032 第四军医大学唐都医院疼痛生物医学研究所

目的探讨大黄总蒽醌对SD大鼠的泻下效应及对结肠水通道蛋白4(aquaporin4,AQP4)表达的影响及大黄酸、大黄素对体外培养LoVo细胞AQP4的调节效应。方法雄性SD大鼠24只随机分为正常对照组、大黄总蒽醌泻下剂量组及高剂量组,分别予大黄总蒽... 详细信息

目的探讨大黄总蒽醌对SD大鼠的泻下效应及对结肠水通道蛋白4(aquaporin4,AQP4)表达的影响及大黄酸、大黄素对体外培养LoVo细胞AQP4的调节效应。方法雄性SD大鼠24只随机分为正常对照组、大黄总蒽醌泻下剂量组及高剂量组,分别予大黄总蒽醌悬液或蒸馏水灌胃5天,观察大鼠结肠粪便含水量;应用Western blot、RT-PCR方法观察其近端结肠AQP4表达的变化。体外培养LoVo细胞并予不同浓度大黄酸/大黄素含药培养液作用24 h及大黄酸/大黄素含药培养液(20 mg/L)不同时间作用,采用Western blot及RT-PCR检测AQP4蛋白及mRNA的表达。结果大黄总蒽醌泻下剂量组及高剂量组作用后,大鼠结肠内粪便含水量明显增加,同时其近端结肠AQP4表达降低且表现为量效关系。大黄酸/大黄素能够显著下调体外培养LoVo细胞的AQP4蛋白及mRNA表达,且表现为剂量-效应及时间-效应关系。结论大黄总蒽醌在发挥泻下作用的同时,能够有效下调大鼠近端结肠AQP4的表达;大黄酸、大黄素可抑制体外培养Lo- Vo细胞AQP4的表达,可能是大黄泻下作用机制之一。

关键词：大黄蒽醌衍生物大黄总蒽醌大黄酸大黄素近端结肠泻下作用 LoVo细胞系水通道蛋白4

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大黄素对LoVo细胞水通道蛋白2表达的调节效应

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中草药 2008年第5期39卷 718-723页

作者：张文生李锋鲍军强王胜春尚刚伟李军昌王长海第四军医大学西京医院中医科暨全军中医内科专科中心陕西西安710032 第四军医大学西京医院药剂科陕西西安710032 第四军医大学唐都医院疼痛生物医学研究所陕西西安710038

目的探讨大黄素对体外培养LoVo细胞水通道蛋白2(aquaporin 2,AQP2)表达的调节效应。方法体外培养LoVo细胞并予不同质量浓度大黄素含药培养液24 h处理及大黄素含药培养液(20 mg/L)不同时间处理,采用免疫细胞化学方法观察LoVo细胞AQP2蛋... 详细信息

目的探讨大黄素对体外培养LoVo细胞水通道蛋白2(aquaporin 2,AQP2)表达的调节效应。方法体外培养LoVo细胞并予不同质量浓度大黄素含药培养液24 h处理及大黄素含药培养液(20 mg/L)不同时间处理,采用免疫细胞化学方法观察LoVo细胞AQP2蛋白表达位置并初步观察AQP2蛋白表达的变化趋势,采用Western blotting及半定量RT-PCR检测AQP2蛋白及mRNA的表达。结果AQP2表达于LoVo细胞的细胞膜,且与大黄素用药浓度及用药时间存在着相关性。进一步的Western blotting证实,不同质量浓度大黄素含药培养液均可抑制AQP2蛋白的表达,药物质量浓度愈大,AQP2蛋白的表达愈低,其中大黄素20 mg/L组及40 mg/L组AQP2蛋白表达显著性降低;大黄素作用3、6 h组,AQP2蛋白表达上升,但与对照组比较,无显著差异;作用12、24、48 h组,AQP2蛋白表达呈进行性下降趋势。半定量RT-PCR结果显示,随着大黄素质量浓度的增加,AQP2 mRNA表达呈进行性下降趋势;在时间-效应方面,随着用药时间的延长,AQP2 mRNA表达呈进行性下降趋势。结论大黄素可抑制LoVo细胞AQP2基因转录与翻译,这提示大黄素对AQP2表达的调节效应可能与大黄的泻下作用有关。

关键词：大黄素 LoVo细胞系水通道蛋白2

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