Reversing pathological neural activity using targeted plasticity

Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations. However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing tones with brief pulses of vagus nerve stimulation completely eliminated the physiological and behavioural correlates of tinnitus in noise-exposed rats. These improvements persisted for weeks after the end of therapy. This method for restoring neural activity to normal may be applicable to a variety of neurological disorders.     

癌痛及其处理对癌症患者生存质量的影响

目的 :探讨癌痛及其处理对癌症患者生存质量的影响。方法 :对 4 8例癌痛患者采用线段分级法(VAS)和 KPS评分法于治疗前后进行评估。结果 :无论是轻度、中度还是重度疼痛 ,均严重影响患者的日常生活、情绪、行走能力、工作、睡眠 ,且随着疼痛程度的加重 ,影响也逐渐加深 ;经三阶梯止痛法治疗后生存质量明显提高 ,治疗前后比较有显著的差异 (P<0 .0 5 )。结论 :疼痛是影响癌症患者生存质量的一个重要因素 ,对癌痛患者应给予必要的止痛治疗 ,以提高患者的生存质量     

结肠镜复位术治疗慢性肠扭转引起不完全性肠梗阻30例临床分析

目的探讨结肠镜复位术治疗慢性结肠扭转引起的不完全性肠梗阻的临床经验.方法对30例慢性结肠扭转引起不完全性肠梗阻患者通过结肠镜复位治疗的疗效进行分析.结果 30例反复出现不完全性肠梗阻患者经结肠造影或结肠镜诊断为存在结肠扭转,局部肠管扭曲严重,除外其他因素引起不完全性肠梗阻,所有患者经结肠镜复位术治疗后腹痛、腹胀、便秘等不适症状明显缓解,无恶心、呕吐症状,能自主排气、排便.结论临床上反复出现痉挛性腹痛、腹胀及恶心、呕吐、排气、排便减少的老年患者和便秘患者,应考虑存在慢性结肠扭转的可能,经结肠镜诊断后即可行肠镜复位术治疗,该术式成功率高,风险小,术后腹痛、腹胀及便秘等不适症状可明显缓解.     

Reversal of pathological pain through specific spinal GABAA receptor subtypes

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.     

The neural mechanisms of pain-related affect and memory

The pain experience includes a sensory-discriminative and an emotional-affective components. The affective dimension refers to the unpleasantness or aversion of sensation. The great progress at the genetic, molecular, cellular, and systemic levels on the study of the sensory dimension of pain has been made over past four decades. However, “to consider only the sensory features of pain, and ignore its motivational and affective properties, is to look at only part of the problem and not even the most important part of that”. A line of clinic observations indicate that the patients with chronic pain suffer from much more affective disturbance than pain itself. Obviously, physiological arousal and hypervigilance to pain cause negative affect, such as anxiety, anger, worry, aversion, even tendency of suicide, these negative affective states in turn enhance pain sensation. Today, more and more attention has been paid to the study on mechanisms underlying affective dimension of pain. In order to deepen and expand our understanding of the nature of pain, this review summarizes the main progress and recent findings from our laboratory regarding affective component of pain in neuroanatomy, neurophysiology, and cell biochemistry.     

运动疗法对慢性下腰痛的康复研究

目的:探讨运动疗法对慢性下腰痛的康复功效;方法:采用文献资料法、实验法以及数理统计法进行研究;将符合本实验纳入标准和排除标准的18例慢性下腰痛患者,进行为期一个月的运动疗法治疗;结果:18例患者腰部疼痛度明显减轻,VAS实验前后数据成显著性差异(P0.01);腰部活动度得到改善(P0.01);腰部肌肉力量增长(P0.01);本体感觉偏离度改善较小(P0.01);结论:运动疗法对下腰痛有显著疗效。     

杏仁核在疼痛及疼痛引起的情感和认知障碍中的作用

疼痛是一种不愉快的感觉和情绪体验, 伴随有强烈的负性情绪(如厌恶、恐惧、焦虑等)。 杏仁核作为边缘系统的皮质下中枢,在情绪反应中具有重要作用。我们的研究表明杏仁核在疼痛调制,特别是疼痛情绪反应中起关键作用。本文综述了杏仁核在疼痛及疼痛引起的焦虑行为和认知功能障碍中的作用。     

电热药物治疗带治疗神经病合并疼痛100例疗效观察

目的：研究电热药物治疗带,对某些神经病合并疼痛的治疗效果。方法：通过对各种神经病合并疼痛病人的治疗前后临床观察,解决了慢性疼痛单纯药物治疗效果较差的问题。结果：电热药物治疗带对退行性骨关节病变、慢性肌肉损害所致疼痛疗效较好。而对枕神经、耳大神经等单神经痛疗效较差。结论：电热药物治疗带,在热疗基础上辅以活血化瘀止痛的消痛散（中药）,加强其治疗效果,改善局部血液循环,疗效达93％,此治疗带适用于各种慢性损伤,尤以运动系统各组织、骨骼、关节、肌肉、肌腱等慢性损害疗效较为满意。     

戴望舒前期诗作的现代性解读

从现代性的角度对戴望舒前期诗作进行解读,可知其在传统与现代之间的徘徊中表现出的忧郁、痛苦、迷茫的思想与情感。     

探寻卡夫卡小说的社会意义——对《变形记》指引“苦痛”的思考

《变形记》作为卡夫卡短篇小说的代表作,以其真实的细节、象征、反讽等独特的艺术形式构筑出一个梦魇般的生活世界,具有独特的美学价值。然而其作为文学的功用不仅于此,它指引出现代人当下的生存困境及个体生命的苦痛,在唤醒我们对于自身主体意识关注的同时,引导我们以自省的姿态去改变令人不满的生存状态,探寻实现个体生命与社会和谐的途径,彰显着巨大的社会意义。     

故乡风景与“怀乡人”面相——基于鲁迅《故乡》与莫言《白狗秋千架》的比较分析

在传统的“归乡叙事”中，对故土风景和人事的回忆和描述是故事的主题。鲁迅因循《故乡》中残旧破碎的“风景’’确立自己的启蒙者角色，并呼应其内心的悲痛和焦虑。《白狗秋千架》中的莫言则在传统的“归乡叙事’’之上，更多地复原故乡“风景”的多面之相，不仅消解了启蒙的意味，在更深的层面上，展示了故乡旺盛狂野的生命力。联系两部作品产生时的历史语境，可以一窥“怀乡人”面目。     

Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain

Modern pain-control theory predicts that a loss of inhibition (disinhibition) in the dorsal horn of the spinal cord is a crucial substrate for chronic pain syndromes. However, the nature of the mechanisms that underlie such disinhibition has remained controversial. Here we present evidence for a novel mechanism of disinhibition following peripheral nerve injury. It involves a trans-synaptic reduction in the expression of the potassium-chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways. In our experiments, the resulting shift in the transmembrane anion gradient caused normally inhibitory anionic synaptic currents to be excitatory, substantially driving up the net excitability of lamina I neurons. Local blockade or knock-down of the spinal KCC2 exporter in intact rats markedly reduced the nociceptive threshold, confirming that the reported disruption of anion homeostasis in lamina I neurons was sufficient to cause neuropathic pain.     

改良肾大部切除大鼠诱发慢性肾衰模型的建立

对5/6切除大鼠肾脏诱发其慢性肾功能衰竭的动物模型进行改良,该方法省时省力,可以减少麻药用量不当造成的大鼠死亡,随差血肌酐(Scr)、尿素氮(BUN)的增加,肾衰逐渐加重,为药理研究及筛选治疗慢性肾衰的有效药物提供了一种实验对象。     

沙尘污染对长期暴露人群呼吸系统症状的影响

以沙尘天气多发的甘肃省民勤县和基本不受沙尘污染的平凉市为调查点,采用流行病学现况调查法,对在调查点长期居住、无职业性粉尘接触史的40岁以上728名农民进行呼吸系统症状发生状况调查.结果显示,民勤县农民慢性咳嗽、咳嗽加重、慢性咳痰、咳痰加重、呼吸困难加重及胸痛加重的发生率分别是平凉市的1.6,5.0,1.7,3.6,1.6,3.7倍(P＜0.05);除呼吸困难加重外,民勤县不吸烟农民上述症状发生率分别是平凉市的1.8,4.9,1.9,2.9,3.9倍(P＜0.05);民勤县女性慢性咳嗽、咳嗽加重、慢性咳痰及胸痛加重发生率分别是平凉市的1.7,4.3,1.8,3.5倍(P＜0.05),男性咳嗽加重及慢性咳痰发生率分别是平凉市的10.0,1.5倍(P＜0.05);民勤县40～50岁农民慢性咳嗽、咳嗽加重、慢性咳痰、胸痛加重发生率分别是平凉市的1.8,9.4,2.1,6.0倍(P＜0.05).沙尘污染明显影响暴露人群呼吸系统症状的发生,主要影响40～50岁人群,尤其是女性.     

不同手术方式治疗腹股沟疝气效果分析

目的:对比不同手术方式治疗腹股沟疝气的临床疗效,为选择合理有效的手术方式提供指导。方法 :收集我院2010年11月到2012年3月期间110例行腹股沟疝气手术患者的临床资料,按照不同的手术方式将其分为平片式无张力疝修补术组(56例)及填充式无张力疝修补术组(54例),比较两组手术患者围手术期的临床指标(手术时间、出血量、住院时间、术后疼痛、并发症),术后随访1年,对比其术后恢复情况。结果:两组手术患者临床指标差异无统计学意义(P>0.05)。结论:较填充式无张力疝修补术相比,平片无张力疝修补术具有解剖清晰、术后并发症发生率低等特点,但是需根据个体化选择手术方式和修补材料,能够有效地降低甚至是避免并发症的产生。     

下颌骨弥散型硬化性骨髓炎的病因与治疗研究现状(综述)

下颌骨弥散型硬化性骨髓炎(DSO)表现为受累下颌骨反复发作的肿痛伴张口受限，X片表现为弥漫性骨硬化伴骨溶解；组织学改变主要为骨硬化伴不规则骨增生、骨髓由纤维组织取代、骨内可见典型的淋巴细胞与浆细胞浸润。其病因的假说有(1)下颌骨的炎症、(2)SAPHO综合征的局部表现、(3)慢性肌腱膜炎等。主要治疗手段有(1)药物治疗、(2)手术治疗等。     

胃食管反流性疾病与呼吸系统疾病（综述）

胃食管反流病（GERD）十分常见,它是一种病理生理基础可涉及多个领域、学科的疾病。对GERD与哮喘、睡眠呼吸暂停综合征、医院内肺炎、反流性咽喉炎、慢性咳嗽、不明原因胸痛、肺纤维化等呼吸系统疾病的关系作一综述。     

Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence

Morphine is a powerful pain reliever, but also a potent inducer of tolerance and dependence. The development of opiate tolerance occurs on continued use of the drug such that the amount of drug required to elicit pain relief must be increased to compensate for diminished responsiveness. In many systems, decreased responsiveness to agonists has been correlated with the desensitization of G-protein-coupled receptors. In vitro evidence indicates that this process involves phosphorylation of G-protein-coupled receptors and subsequent binding of regulatory proteins called beta-arrestins. Using a knockout mouse lacking beta-arrestin-2 (beta arr2-/-), we have assessed the contribution of desensitization of the mu-opioid receptor to the development of morphine antinociceptive tolerance and the subsequent onset of physical dependence. Here we show that in mice lacking beta-arrestin-2, desensitization of the mu-opioid receptor does not occur after chronic morphine treatment, and that these animals fail to develop antinociceptive tolerance. However, the deletion of beta-arrestin-2 does not prevent the chronic morphine-induced up-regulation of adenylyl cyclase activity, a cellular marker of dependence, and the mutant mice still become physically dependent on the drug.     

教师常见职业病的成因及其防治——一次健康采点调查的启示

本文介绍了教师中常见职业病(失眠症、胃病、慢性喉炎,腰腿痛)的现状、发病原因、临床表现等。有针对性的提出了防治措施。     

论《赵氏孤儿》的悲剧快感

《赵氏孤儿》是著名的古典悲剧,给人带来悲的世界,但这种悲不是绝望的悲,是一种给人奋发向上的悲。悲剧中既有痛感的体现,也有一种快感在其中。讨论《赵氏孤儿》戏剧的悲剧快感,主要从韩厥两难处境、屠岸贾的过场作用对《赵氏孤儿》加以审美的分析和提炼,从艺术自身的角度看待《赵氏孤儿》方能体会到它长久不衰的魅力。