笔者想承认CCI模型贝内特和谢（1988）的原始描述。 部分支持这项工作是由国家健康与澳大利亚医学研究理事会（编号568637）和新南威尔士州办事处资助科学和医学研究为GMT。

1。慢性坐骨神经无菌技术应该用于外科手术。外科工作表面用70％乙醇消毒和灭菌准备提前无菌文书（例如，罚款的剪刀，镊子，拉钩），纱布，订书钉和棉签。对于多次手术，清洁，并用70％乙醇或干大鼠之间的珠灭菌器resterilise文书。应戴口罩，头发的帽子和无菌手套。 收缩的神经，切成约3厘米长的小件浸泡在无菌生理盐水准备铬肠缝合，以防止干燥。关闭伤口，使用市售无菌丝线。 <ol><li>在室使用在O 2 5％异氟醚诱导的大鼠麻醉，然后提供2％异氟醚在O 2，通过自定义作出口罩和监测在程序的anesthetised的动物。常见的替代麻醉药吸入氟烷或腹腔钠苯巴比妥。作为N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，氯胺酮，应避免，因为这些受体在神经性疼痛的发展的重要。 </li><li>刮胡子的大鼠的左后腿。然后，放置到一个热调节的加热垫的动物在37℃，适用于润滑眼药膏的眼睛。 </li><li>三个70％的异丙醇和碘溶液备用应用消毒剃光面积。 </li><li>与老鼠躺在其胸部/胸部，提升左后腿和中与的femor位置保持在90°至脊椎上使用脚胶带。 </li><li>请在皮肤切口平行，但低于femor 3-4毫米，并从皮肤由通过结缔组织切割的切口周围的肌肉。 </li><li>使用钝的剪刀，切通过臀肌浅和二头肌之间的结缔组织，股四头肌肌肉。 </li><li>使用拉钩扩大两肌肉之间的差距，使坐骨神经清晰的可视化。 </li><li>使用弯曲的钝头镊子，微型剪刀，轻轻地约10毫米坐骨神经周围结缔组织（近端的坐骨神经trifurcation的）。 </li><li>在显微镜下和良好的光源，配合双结连字（铬肠4.0，爱惜康，美国），相距1毫米到坐骨神经trifurcation的，近端。对于每个结扎，用一个单一的宽松循环的开始，然后抓住接近循环的两端，并拧紧，直到循环只是勉强舒适和沿神经结扎不滑动。举行的循环在适当的位置，放置第一完成结上的第二个循环。最后，周边1mm结扎切断，有始有终。收缩的神经应该是最小的，如果观察一个简短的抽搐立即停止，以防止日逮捕Ëepineural血流量。导致过度拧紧了结扎切断，自残（自残），既不必要的副作用，其中排除成功疼痛过敏测试。 </li><li>使用缝线（Mersilk 5.0，爱惜康）关闭固定皮肤肌肉层和主食（Autoclip，9毫米）。接下来，用碘液（Riodine）消毒伤口。 </li><li>密切观察大鼠在麻醉恢复期，并允许它恢复在单独的笼子里，平板纸的床上用品（标准畜牧业床上用品的），为了防止无意识的动物窒息。 给予任何手术后镇痛的调查之前，应考虑到这可能会干扰与疼痛过敏测试。事实上，有证据表明局部麻醉，利多卡因，在伤停补时阶段的应用，可以改变神经痛的发展，并减少前7周的痛觉过敏程度。为进一步讨论这个M东北黑钙土看到8 Bennett 等人的审查。 </li></ol> 2。疼痛行为的测量<ol><li>在实验开始前几天，每天处理的大鼠建议，以习惯的老鼠，其处理程序，减少咬的压力和风险。 </li><li>行为测试之前，需要习惯于大鼠的测试程序和动物外壳。测试环境应保持安静，并很好的控制，具有恒定的温度和湿度水平，每个测试会话类似在一天的时间进行。 </li><li>疼痛过敏测试应执行之前，C​​CI（基线）和CCI后不同时间点几次，所需。 </li></ol> 3。机械痛阈值<ol><li>在一天的测试，地方大鼠成高架地板测试网笼15-30分钟前撤回阈值测量，允许笼勘探和groo的的明活动，停止和老鼠变得轻松和平稳。 </li><li>使用一个动态的足底冯弗雷触觉乌戈·巴西莱（意大利），位置与长丝触摸刺激单位直接下中旬的后肢足底表面，避免了金属丝网，按开始键。这升降机的机械刺激增加力量的后肢足底表面的长丝。 </li></ol>手册·冯·弗雷毛发一系列增加直径校准诱导特定的力量时，适用于皮肤的细丝。它们可以被用来作为替代电子动态足底冯弗雷测量缩爪阈值，如前面所述4触觉。也有电子冯·弗雷aesthesiometers（如印约理事会），美国，瑞典和Somedic几种可供选择的制造商。 <ol start="3"><li>记录从受伤和健侧hindpa机械撤出门槛WS，在平衡重的顺序。此装置适用于压力的爪子和戒断反应时，系统会自动记录和显示应用（克）的最大力量。如果一个含糊的反应时（即在行走或修饰的情况下），重复的刺激，并再次记录阈值。后肢刺激后舔或晃动，伴有疼痛是一种行为的迹象。 </li><li>重复机械性刺激与刺激之间约5分钟的间隔的3倍，记录阈值，然后计算缩爪阈值的平均值。 </li></ol> 4。热退缩潜伏期在实验开始前，应调整的红外（IR）的足底测试仪器的热强度。在我们的实验室中，我们调整给天真大鼠约10秒平均爪退缩潜伏期的红外线强度，我们定在20秒截止延迟，以避免组织大坝年龄失败删除爪子的情况下。 <ol><li>在一天的测试，地方大鼠成玻璃地板测试测量延迟15-30分钟前笼，允许笼勘探和疏导活动，停止和大鼠变得轻松和平稳。 </li><li>使用直接下中旬足底表面的后肢足底热镇痛仪（乌戈·巴西莱，意大利），位置的红外源，按下启动键。这暴露的后肢足底表面的热辐射光束通过一个透明的玻璃表面。也有替代足底热镇痛手段（如印地安人条约理事会，美国和Stoelting，美国）制造商。 </li><li>记录从受伤和未受伤的后爪退缩潜伏期，在平衡重的顺序。此装置会自动记录撤回爪子从热源热刺激发病（秒）的时间。如果发生一个含糊的反应（即在案件ambulaTION或修饰），重复的刺激和记录再次延迟。后肢刺激后舔或晃动，伴有疼痛是一种行为的迹象。 </li><li>约5分钟刺激之间的间隔至少3次重复热刺激，记录的潜伏期，然后计算平均缩爪潜伏期。 </li></ol> 4。代表结果机械撤出阈值和热退缩潜伏期大鼠同侧（受伤）和对侧（健侧）的爪子的一个例子是前（基线）和CCI 图3A和图3B后2-12天。从这些数字可以看出，CCI导致机械撤回阈值和同侧后肢热撤出潜伏期显着减少，说明存在的机械和热痛过敏，慢性神经痛两种功能<html> 。 <img alt="图1" src="/files/ftp_upload/3393/3393fig1.jpg" /> 图1。示意图说明CCI模型结扎的定位。这种神经性疼痛的动物模型，涉及四个宽松的铬肠结扎坐骨神经在大腿中部的水平，安置。它导致受伤，只有部分的传入脚和随后的后肢疼痛过敏。 <img alt="图2" src="/files/ftp_upload/3393/3393fig2.jpg" /> 图2。疼痛测试使用的后肢面积图。中期跖面的脚垫后，由红色虚线圆圈表示，用于疼痛测试。坐骨神经末端分支支配，大多是由该区域。脚跟和脚掌，应避免由于差分皮肤敏感。 3.JPG"/&gt; 图3。在大鼠坐骨神经慢性收缩后的疼痛过敏。 CCI后，有一个缩爪阈值显着减少机械刺激（A）和（B）在受伤的热刺激缩爪潜伏期（同侧），后肢比健侧（对侧）后肢（P均&lt;0.01重复测量2方差分析）。数据显示，平均±SEM，每组7只大鼠。

<ol>
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M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Different+strains+and+substrains+of+rats+show+different+levels+of+neuropathic+pain+behaviors.">Different strains and substrains of rats show different levels of neuropathic pain behaviors.</a> Experimental Brain Research. 129, 167-171 (1999).</li><li>Mogil, J. S., Davis, K. D., Derbyshire, S. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+necessity+of+animal+models+in+pain+research.">The necessity of animal models in pain research.</a> Pain. 151, 12-17 (2010).</li><li>Mogil, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+pain:+progress+and+challenges.">Animal models of pain: progress and challenges.</a> Nat. Rev. Neurosci. 10, 283-294 (2009).</li><li>Langford, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coding+of+facial+expressions+of+pain+in+the+laboratory+mouse.">Coding of facial expressions of pain in the laboratory mouse.</a> Nat. Methods. 7, 447-449 (2010).</li><li>Austin, P. J., Moalem-Taylor, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neuro-immune+balance+in+neuropathic+pain:+involvement+of+inflammatory+immune+cells,+immune-like+glial+cells+and+cytokines.">The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines.</a> J. Neuroimmunol. 229, 26-50 (2010).</li></ol>

动物实验，澳大利亚新南威尔士大学的动物护理和伦理委员会批准，并随后由国际疼痛研究协会发出的指引。

CCI是一种广泛使用的外周神经损伤模型慢性神经痛。它是相对简单的执行，并产生损伤后一个月至少有一个强大和稳定的疼痛过敏。继CCI的，大鼠表现出受伤的后肢（一起举行的脚趾和足底弯曲，脚掌外翻），以及反复晃动，守卫和受伤的暗示在场的自发痛9后肢舔的姿势异常。除了 ​​感觉障碍，一些调查显示，CCI的唤起行为障碍，如扰乱社会互动，睡眠障碍，抑郁和焦虑样行为10-13，但是这是在未能找到这样的行为障碍由他人14,15。因此，CCI是常用调查的病理生理，和潜在的治疗药物，用于治疗神经性疼痛。 我们DESCR国际教育局单方面收缩左侧坐骨神经，但应注意到，许多实验者右侧坐骨神经CCI类似的疼痛和行为结果，。一些研究者可能会发现它更容易执行在一个特定的方面，由于霸道的手术，在实验中切换，而其他方面排除任何偏见。值得注意的是，已包括使用周围神经16,17只有2结扎，缝合材料铬，如纯肠道和polyglactin（vicryl）18,19在大鼠肠道以外的原程序的几个变化。 CCI模型，此外，也利用小鼠进行了修改，其中的过程是相同的，除了使用2-3结扎与各种缝合材料，包括铬羊肠线，尼龙，和普理灵15,20,21。 这种模式的一个限制是CCI的大鼠之间的变异程度，由于variabiliTY缝线结绳记事生产的缢胸闷。这可以部分克服由有经验的研究员，以一致的方式进行手术。此外，用于结扎神经缝合材料的类型，也可以作出贡献的可变性，它被认为化学品从铬肠道调解19,22在这个模型中观察到的一些行为和神经化学影响。特别应考虑到大鼠性别（男性与女性）23岁（青年与老）24,25，饮食26和27株，它可以显着地影响疼痛过敏的发展后，CCI的选择。 疼痛过敏测试，使用电子冯·弗雷触觉或手动用von Frey机械撤出门槛和足底镇痛（哈格里夫斯）米热退缩潜伏期的毛发，以及建立和重新疼痛过敏的小动物的责任量化措施。它们的使用，在与神经性疼痛模型相结合，广泛和允许直接爪子跨越不同的治疗方案的机械和热刺激的敏感性比较，大鼠不同菌株之间。应当指出的是，其他如针点刺试验和冷痛觉异常行为检测，也用于测试CCI引起的疼痛过敏8。 同时，使用自反撤出机械或热刺激是在这个模型和其他神经性疼痛的重大举措，它最近被批评其与人类的症状和参与相当实验者偏见28的相关性较差。因此，使用29疼痛和自发发射的行为30操作性的措施，如额外的典范，将是有益的。 然而，DESpite这些限制，CCI模型和缩爪测量疼痛过敏测试是为了解神经性疼痛的机制，并确定新的止痛目标的关键。在我们的实验室中，我们经常执行CCI和测量机械缩足阈值和热爪子撤出潜伏期，以了解神经免疫的相互作用有助于神经痛31，评估调节免疫系统的潜力，以减轻疼痛过敏。

<table border="1"><tbody><tr><td> 试剂/设备名称 </td><td> 公司 </td><td> 目录编号 </td><td> 评论 </td></tr><tr><td>艳色肠道</td><td>爱惜康</td><td>的G-211 </td><td> 4-0厚度</td></tr><tr><td>异氟醚</td><td> delvet Pty有限公司，七山，新南威尔士州</td><td> N / A </td><td></td></tr><tr><td> mersilk </td><td>爱惜康</td><td>的W-580 </td><td> 5-0厚度</td></tr><tr><td> autoclip </td><td>碧迪</td><td> 427631 </td><td> 9毫米的不锈钢</td></tr><tr><td> riodine </td><td>猎户座</td><td> R1000802F </td><td> 1％W / V碘</td></tr><tr><td>足底热镇痛仪</td><td>乌戈·巴西莱</td><td> 37370 </td><td></td></tr><tr><td>动态跖触觉的</td><td>乌戈·巴西尔é </td><td> 37400 </td><td></td></tr></tbody></table>

chronic constriction of the sciatic nerve and pain hypersensitivity testing in rats

慢性神经性疼痛，从中央或周围神经系统的损害，是一种普遍的和虚弱的状态，影响7-18人口的1,2％。症状包括自发性疼痛（刺痛，烧灼，电休克一样），感觉迟钝，感觉异常，痛觉异常（通常非疼痛刺激产生疼痛）和痛觉过敏（增加疼痛刺激的反应）。感觉症状与行为障碍，如失眠和抑郁，病态的合作。为了研究慢性神经痛几个模仿周围神经损伤的动物模型已开发，使用最广泛的是贝内特和谢的（1988）单方面坐骨神经慢性压迫性损伤（CCI）3（ 图1）。在这里，我们提出一个表演CCI和测试疼痛过敏的方法。 CCI是在麻醉下进行，一方面通过使暴露坐骨神经亲属的切口，并通过切割之间的臀肌浅和股二头肌肌肉结缔组织。四个铬肠道结扎坐骨神经周围松散地绑在1毫米的间隔，只是阻挡而不是逮捕epineural的血流量。关闭伤口缝合肌肉和皮肤中的主食。然后，动物被允许恢复从手术前24小时开始疼痛过敏测试。 行为测试，老鼠被放入测试设备，并允许习惯于测试过程。测试的区域是中旬的后肢跖面（ 图2），属于坐骨神经分布区域内。通过机械刺激使用电子动态足底冯弗雷触觉或手册·冯·弗雷毛发4受伤和未受伤的后爪机械痛阈值评估。机械撤出门槛是施加最大的压力（克），触发爪子撤出。热退缩潜伏期哈格里夫斯等人 （1988）首次描述，测量，后肢被暴露在辐射热束通过一个透明的玻璃表面，使用足底镇痛米5,6。记录的时间为受伤和未受伤的后爪缩爪退缩潜伏期的热量刺激。继CCI的，机械的退出门槛，以及受伤的爪子热退缩潜伏期均明显减少，比基线测量和未受伤的爪子（ 图3）。周围神经损伤与疼痛过敏测试相结合的CCI模型提供了一个模型系统调查的潜在治疗药物的有效性，修改慢性神经性疼痛。在我们的实验室中，我们利用热和机械灵敏度的后爪一起CCI调查的发病机制的神经免疫相互作用的作用治疗神经性疼痛。

Watch this Scientific Journal Video about Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats at JoVE.com

Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats

由于手术简单和健壮的行为结果，坐骨神经慢性缩窄是神经​​痛卓越的动物模型之一。手术后24小时内，疼痛过敏建立并可以使用冯弗雷触觉（机械测试）和足底的镇痛米（热试验）的定量测​​定。

慢性缩窄大鼠坐骨神经疼痛过敏测试

Chronic neuropathic pain, resulting from damage to the central or peripheral nervous system, is a prevalent and debilitating condition, affecting 7-18% of ...

chronic-constriction-sciatic-nerve-pain-hypersensitivity-testing

Nanyang Technological University

Research

JoVE Journal

Medicine

58.6K 次观看.  University of New South Wales. 由于手术简单和健壮的行为结果，坐骨神经慢性缩窄是神经​​痛卓越的动物模型之一。手术后24小时内，疼痛过敏建立并可以使用冯弗雷触觉（机械测试）和足底的镇痛米（热试验）的定量测​​定。

视频: Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory testing in rat SCI models is needed. However, until recently, no single testing approach had been validated for SCI so that standardized methods have not been implemented across labs. Additionally, available testing methods could not be implemented acutely or when severe motor impairments existed, preventing studies of the development of SCI-induced allodynia3. Here we present two validated sensory testing methods using von Frey Hair (VFH) monofilaments which quantify changes in tactile sensory thresholds after SCI4-5. One test is the well-established Up-Down test which demonstrates high sensitivity and specificity across different SCI severities when tested chronically5. The other test is a newly-developed dorsal VFH test that can be applied acutely after SCI when allodynia develops, prior to motor recovery4-5. Each VFH monofilament applies a calibrated force when touched to the skin of the hind paw until it bends. In the up-down method, alternating VFHs of higher or lower forces are used on the plantar L5 dermatome to delineate flexor withdrawal thresholds. Successively higher forces are applied until withdrawal occurs then lower force VFHs are used until withdrawal ceases. The tactile threshold reflects the force required to elicit withdrawal in 50% of the stimuli. For the new test, each VFH is applied to the dorsal L5 dermatome of the paw while the rat is supported by the examiner. The VFH stimulation occurs in ascending order of force until at least 2 of 3 applications at a given force produces paw withdrawal. Tactile sensory threshold is the lowest force to elicit withdrawal 66% of the time. Acclimation, testing and scoring procedures are described. Aberrant trials that require a retest and typical trials are defined. Animal use was approved by Ohio State University Animal Care and Use Committee.

We describe two tactile sensory testing methods for acute or chronic periods of spinal cord injury in rats. These validated procedures can detect the development and maintenance of allodynia-like sensations.

在大鼠脊髓损伤后的急性和慢性触觉测试

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory ...

科研

医学

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50&#8211;60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using trans-thoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.

We describe a stepwise procedure for creating pressure overload and left ventricular hypertrophy in Wistar rats by constriction of the ascending aorta using a small metallic clip. This model is extensively used for studying remodeling changes during cardiac hypertrophy and for identifying and evaluating strategies for regression of such changes.

大鼠建立压力超负荷心肌肥厚模型在升主动脉缩窄

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart ...

Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination, as well as nocturia and general pelvic pain, especially upon bladder filling or voiding. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. One such murine model is urinary bladder distension (UBD). In this model, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure, wires in the superior oblique abdominal muscles record electrical activity from the muscle. This activity is known as the visceromotor response (VMR) and is a reliable and reproducible measure of nociception. Here, we describe the steps necessary to perform this technique in mice including surgical manipulations, physiological recording, and data analysis. With the use of this model, the coordination between primary sensory neurons, spinal cord secondary afferents, and higher central nervous system areas involved in bladder pain can be unraveled. This basic science knowledge can then be clinically translated to treat patients suffering from IC/BPS.

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized in part by pelvic pain. In order to study nervous system contributions to the condition, a physiological model of urinary bladder pain is used in mice and rats.

膀胱胀诱发内脏运动反应为膀胱疼痛小鼠模型

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition ...

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in injured sensory neurons and along the entire nociceptive pathway within the central nervous system. It is usually chronic and challenging to treat. In order to study neuropathic pain and its treatments, different models have been developed in rodents. These models derive from known etiologies, thus reproducing peripheral nerve injuries, central injuries, and metabolic-, infectious- or chemotherapy-related neuropathies. Murine models of peripheral nerve injury often target the sciatic nerve which is easy to access and allows nociceptive tests on the hind paw. These models rely on a compression and/or a section. Here, the detailed surgery procedure for the &#34;cuff model&#34; of neuropathic pain in mice is described. In this model, a cuff of PE-20 polyethylene tubing of standardized length (2 mm) is unilaterally implanted around the main branch of the sciatic nerve. It induces a long-lasting mechanical allodynia, i.e., a nociceptive response to a normally non-nociceptive stimulus that can be evaluated by using von Frey filaments. Besides the detailed surgery and testing procedures, the interest of this model for the study of neuropathic pain mechanism, for the study of neuropathic pain sensory and anxiodepressive aspects, and for the study of neuropathic pain treatments are also discussed.

Neuropathic pain is a consequence of a lesion or disease affecting the somatosensory system. The &#8220;cuff model&#8221; of neuropathic pain in mice consists of the implantation of a polyethylene cuff around the main branch of the sciatic nerve. Mechanical allodynia is tested using von Frey filaments.

神经病理性疼痛小鼠坐骨神经掴型号

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in ...

Chronic Constriction Injury of the Rat's Infraorbital Nerve (IoN-CCI) to Study Trigeminal Neuropathic Pain

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral procedures to study trigeminal neuropathic pain in rats. To meet the specificity of trigeminal neuropathic pain syndromes, the infraorbital nerve (IoN) is subjected to a chronic constriction injury (CCI) by loosely ligating the nerve. An intra-orbital approach is presented here to expose and ligate the IoN in the orbital cavity. After IoN ligation, rats exhibit changes in spontaneous behavior and in response to von Frey hair stimulation that are indicative of persistent pain and mechanical allodynia. Two phases can be defined in the development of the behavioral changes. During the first week following IoN-CCI (phase 1), rats show an increased and asymmetric face grooming activity, i.e., with face wash strokes primarily directed to the nerve-injured IoN territory. A distinction is made between face grooming behavior that is part of a more general body grooming behavior, which remains largely unaffected by IoN-CCI, and face grooming that is neither preceded nor followed by body grooming, which is significantly increased after IoN-CCI. During this period, responsiveness to mechanical stimulation of the IoN territory is reduced. This hyporesponsiveness is abruptly replaced by an extreme hyperresponsiveness whereby even very weak stimulus intensities provoke nocifensive behavior (phase 2). The phenomenological similarities between these behavioral alterations and reported signs of facial pain (i.e., responses to noxious stimulation of the face) suggest the presence of dysesthesia/paresthesia and mechanical allodynia in the ligated IoN territory.

Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain

This manuscript describes a rodent model to study trigeminal neuropathic pain. The methods described include surgical procedures to perform a chronic constriction injury of the rat&#8217;s infraorbital nerve and the post-surgical behavioral tests to measure the changes in spontaneous and evoked behavior that are indicative of persistent pain and allodynia.

老鼠的眶下神经（ION-CCI）研究三叉神经性疼痛性损伤

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral ...

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death. Hypertensive heart disease is one of the key contributing factors of cardiac remodeling associated with heart failure. The most commonly-used animal model mimicking hypertensive heart disease is created via surgical interventions, such as by narrowing the aorta. Abdominal aortic constriction is a useful experimental technique to induce a pressure overload, which leads to heart failure. The surgery can be easily performed, without the need for chest opening or mechanical ventilation. Abdominal aortic constriction-induced cardiac pathology progresses gradually, making this model relevant to clinical hypertensive heart failure. Cardiac injury and remodeling can be observed 10 weeks after the surgery. The method described here provides a simple and effective approach to produce a hypertensive heart disease animal model that is suitable for studying disease mechanisms and for testing novel therapeutics.

A rat model of abdominal aortic constriction that induces cardiac hypertrophy and remodeling is described. An efficient, highly-reproducible, and minimally-invasive method is used to provide a simple yet useful platform for research in myocardial hypertrophy and dysfunction.

心脏重构通过大鼠腹主动脉缩窄的模型

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and ...

Histological Quantification of Chronic Myocardial Infarct in Rats

Myocardial infarction is defined as cardiomyocyte death due to prolonged ischemia; an inflammatory response and scar formation (fibrosis) follow the ischemic injury. Following the initial acute phase, chronic remodeling of the left ventricle (LV) modifies the structure and function of the heart. Permanent coronary ligation in small animals has been widely used as a reference model for a chronic model of MI. Thinning of the infarcted wall progressively develops to transmural fibrosis. Histological assessment of infarct size is commonly performed; nevertheless, a standardization of the methods for quantification is missing. Indeed, important methodological aspects, such as the number of sections analyzed and the sampling and quantification methods, are usually not described and therefore preclude comparison across investigations. Too often, quantification is performed on a single section obtained at the level of the papillary muscles. Because novel strategies aimed at reducing infarct expansion and remodeling are under investigation, there is an important need for the standardization of accurate heart sampling protocols. We describe an accurate method to quantify the infarct size using a systematic sampling of harvested rat heart and image analyses of trichromatic stained histological sections obtained from base to apex. We also provide evidence that calculating the expansion index (EI) allowed for infarct size assessment, taking into account changes of the left ventricle throughout the remodeling.

The post-mortem assessment of myocardial infarction (MI) in rodents is based on quantification of the infarct on stained heart sections. We describe an accurate method to quantify the infarct size using systematic sampling of harvested rat hearts from base to apex and image analyses of trichrome-stained histological sections.

大鼠慢性心肌梗塞的组织学定量分析

Myocardial infarction is defined as cardiomyocyte death due to prolonged ischemia; an inflammatory response and scar formation (fibrosis) follow the ...

Minimally Invasive Transverse Aortic Constriction in Mice

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard open-chest transverse aortic constriction (TAC). Although transverse aortic constriction is a highly functional method for the induction of high pressure in the left ventricle, it is a more difficult and lengthy procedure due to its use of artificial ventilation with tracheal intubation. TAC is oftentimes also less survivable, as the newer method, MTAC, neither requires the cutting of the ribs and intercostal muscles nor tracheal intubation with a ventilation setup. In MTAC, as opposed to a thoracotomy to access to the chest cavity, the aortic arch is reached through a midline incision in the anterior neck. The thyroid is pulled back to reveal the sternal notch. The sternum is subsequently cut down to the second rib level, and the aortic arch is reached simply by separating the connective tissues and thymus. From there, a suture can be wrapped around the arch and tied with a spacer, and then the sternal cut and skin can be closed. MTAC is a much faster and less invasive way to induce left ventricular hypertension and enables the possibility for high-throughput studies. The success of the constriction can be verified using high-frequency trans-thoracic echocardiography, particularly color Doppler and pulsed-wave Doppler, to determine the flow velocities of the aortic arch and left and right carotid arteries, the dimension of the blood vessels, and the left ventricular function and morphology. A successful constriction will also trigger significant histopathological changes, such as cardiac muscle cell hypertrophy with interstitial and perivascular fibrosis. Here, the procedure of MTAC is described, demonstrating how the resulting flow changes in the carotid arteries can be examined with echocardiography, gross morphology, and histopathological changes in the heart.

Minimally invasive transverse aortic constriction (MTAC) conserves the essentials of regular transverse aortic constriction (TAC) while eliminating the use of a ventilator with tracheal intubation. It proves to be a highly desirable method for high-throughput studies on left ventricular overload, particularly in translational studies.

微创横向主动脉缩窄小鼠

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard ...

Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. Neuromodulation techniques for chronic facial pain include deep brain stimulation and motor cortex stimulation, which are complex to perform. Subcutaneous nerve field stimulation is certified for chronic back pain and is the least invasive form of neuromodulation. We applied this technique to treat chronic and neuropathic trigeminal pain as an individual therapy concept. First, trial stimulation is performed. Subcutaneous leads are placed in the painful trigeminal dermatome under local anesthesia. The leads are connected to an external neurostimulator that applies constant stimulation. Patients undergo a 12 day outpatient trial to assess the effect of the stimulation. Electrodes are removed after the trial. If the patient reports pain reduction of at least 50% in intensity and/or attack frequency, a reduction in medication or increase in quality of life, permanent implantation is scheduled. New electrodes are implanted under general anesthesia and are subcutaneously tunneled to an infraclavicular internal pulse generator. Patients are able to turn stimulation on and off and to increase or decrease the stimulation amplitude as needed.
This technique represents a minimal invasive alternative to other more invasive means of neuromodulation for trigeminal pain such as motor cortex stimulation or deep brain stimulation.

Treating chronic or neuropathic facial pain can be challenging when medical or standard treatment fails. Subcutaneous nerve field stimulation is the least invasive form of neuromodulation and is used for chronic back pain. We applied this technology to treat chronic and neuropathic trigeminal facial pain.

皮下三叉神经场刺激难治性面部疼痛

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. ...

Development of Recombinant Proteins to Treat Chronic Pain

Chronic pain is difficult to treat and new approaches to resolve persistent pain are urgently needed. Anti-inflammatory cytokines are promising candidates for treating debilitating pain conditions due to their capacity to regulate aberrant neuro-immune interactions. However, physiologically they work in a network of various cytokines, and therefore their therapeutic effect may not be optimal when used as stand-alone drugs. To overcome this limitation, we developed a fusion protein of the anti-inflammatory cytokines IL4 and IL10. Here, we describe the methods for production and quality control of IL4-10 recombinant fusion protein and we test the effectiveness of the IL4-10 fusion protein to resolve pain in a mouse model of persistent inflammatory pain.

In this paper we provide details for the methods of production and quality control of an IL4-10 recombinant fusion protein. We also show how to test the effectiveness of this protein to resolve pain in a mouse model of inflammatory pain.

重组蛋白治疗慢性疼痛的研究进展

Chronic pain is difficult to treat and new approaches to resolve persistent pain are urgently needed. Anti-inflammatory cytokines are promising candidates ...