鞘内注射巴氯芬对镜像痛大鼠机械痛敏的影响

目的探讨鞘内注射巴氯芬对镜像痛大鼠机械痛敏的影响。方法选取SD大鼠40只,随机分为3组：模型组（n=24）、模型对照组（H组,n=8）、正常组（W组,n=8）。将Walker256乳腺癌细胞注入左侧胫骨髓腔制备大鼠癌痛模型,然后将模型组大鼠24只,随机分成3组（n=8）：Ⅰ组鞘内注射生理盐水;Ⅱ组、Ⅲ组分别鞘内注射巴氯芬0.1μg及0.3μg。术后9d鞘内给药,注射容积10μl。给药前0.5h（T1）、给药后的0.5、1、2、4、8、24h测定大鼠双足机械缩爪阈值（MWT）、评价运动功能。结果Ⅱ组、Ⅲ组在鞘内给药后0.5h开始痛阈值明显增加,与Ⅰ组比较差异有统计学意义（P〈0.01）;Ⅱ组、Ⅲ组大鼠运动功能不受明显影响。结论鞘内注射巴氯芬可以明显降低由骨癌痛模型引发镜像痛的机械痛敏。     

附子对脊神经结扎大鼠痛阈的影响

 目的 观察附子对脊神经结扎大鼠痛阈的影响,并初步探讨其镇痛机制.方法 24只雄性SD大鼠随机分为正常对照组、神经痛组和附子治疗组,每组各8只.左侧L5脊神经结扎术后8 d,附子治疗组给予附子2 g/kg灌胃,连续5 d,1次/ d;神经痛组给予同等剂量的生理盐水.术前至术后12 d每天检测大鼠痛阈变化.术后12 d取各组大鼠左侧L5和L4及右侧L5 DRG,观察DRG中交感神经纤维及篮状结构数量的变化.结果 附子治疗组大鼠治疗后痛阈逐渐增高,与神经痛组比较差异具有统计学意义(P<0.05);附子治疗组大鼠左侧L5和L4 DRG中TH阳性纤维平均累计光密度明显低于神经痛组,右侧L5 DRG中TH阳性纤维的平均累计光密度在附子治疗前后差异无统计学意义.附子治疗组DRG中篮状结构的数量较神经痛组减少,但两组比较差异无统计学意义.结论 附子确能提高脊神经结扎大鼠的痛阈,其机制可能与抑制脊髓DRG中交感神经的芽生相关.     

经皮神经电刺激大鼠涌泉穴的fMRI表现和对痛阈的影响

目的:观察经皮神经电刺激(TENS)法刺激大鼠涌泉穴的fMRI表现,为揭示针灸镇痛的中枢机制提供可视实验数据。方法:使用热板仪测定大鼠TENS前后痛阈的变化,利用fMRI血氧水平依赖(BOLD)技术获取TENS涌泉穴的脑功能图像,并显示激活区域。结果:实验组TENS 20 min后痛阈值比实验前显著提高,与对照组相比差异有显著性意义;经皮神经电刺激大鼠右足涌泉穴时大脑激活区域有双侧的额叶皮质1区、2区、双侧的扣带皮质1区、2区、对侧的尾壳核、对侧岛叶皮质、皮质后肢代表区和顶皮质1区。结论:TENS后大鼠痛阈显著增高,提示针刺涌泉穴具有镇痛效应;其机制可能与引起中枢内与痛有关的皮层激活,从而使针刺部位的传入冲动在中枢神经系统内整合,并通过调节神经递质和激素的释放而对疼痛产生抑制作用。     

前扣带回NMDA受体NR2A亚单位与睡眠剥夺模型大鼠外周疼痛感受阈值的关系

目的 观察睡眠剥夺(SD)模型大鼠外周疼痛感受阈值的改变及其中枢痛觉感受区域前扣带回兴奋性谷氨酸受体(NMDA)的表达变化.方法 80只雄性SD大鼠随机均分为4组:正常对照(Con)组,睡眠剥夺(SD)24h(SD24h)组,SD48h组及SD72h组.采用小平台水环境法制作睡眠剥夺大鼠模型,采用热敏测试仪测定各组大鼠足底热刺激缩足潜伏期以反映足部热痛阈值的变化.同时采用Western blotting和免疫荧光技术检测大鼠脑组织皮质前扣带回NR2A和NR2B蛋白的表达.结果 SD48h组及SD72h组大鼠热刺激缩足潜伏期分别为6.87±1.56s和5.18±1.15s,较对照组Con组(8.08±1.86s)有明显降低(P<0.05),而SD24h组(7.97±1.58s)与对照组无明显差异.Western blotting检测结果显示,SD48h、SD72h组大鼠脑组织ACC区域NR2A蛋白表达(0.52±0.12,0.57±0.13)较Con组(0.41±0.12)有明显上调(P<0.05),SD24h组(0.43±0.14)与对照组比较无显著性差异;而NR2B的蛋白在各组间的表达(SD24h组、SD48h组、SD72h组和Con组依次为0.68±0.19、0.76±0.18、0.74±0.16和0.74±0.19)的NR2B表达无显著差异.免疫荧光检测结果显示,与Con组(12.04±3.17)比较,SD48h组(15.19±3.56)及SD72h组(16.1±3.88)NR2A表达明显上调(P<0.01),SD24h组(12.59±2.79)无显著差异.NR2B蛋白在各组间的表达(SD24h组、SD48h组、SD72h组和Con组依次为32.51±7.45、34.1±6.78、33.59±5.85、33.04±8.57)无显著差异.结论 睡眠剥夺48h和72h后,大鼠足部痛阈下降,同时伴行脑皮质前扣带回区域NMDA受体NR2A亚单位的表达上调.     

大鼠FK506套管模型与自体神经移植模型脊髓背角c-fos表达的比较研究

目的建立大鼠外消旋聚乳酸/FK506（PDLLA/FK506）复合套管模型和大鼠外周神经自体神经移植神经再生模型,观察对比各模型神经恢复过程中机械痛觉超敏的变化及脊髓背角c-fos表达的改变,探讨两种神经再生模型中神经再生与神经性疼痛的联系。方法雄性Wistar大鼠60只随机分成3组,每组20只。A组为自体神经移植再生模型组;B组为PDLLA/FK506套管修复模型组;C组假手术组。分别制成模型,术后24d起检测机械刺激阈值,术后27d起计数c-fos阳性细胞。结果 A、B组各项指标与C组比较有显著差异（P〈0.05）;A组与B组比较c-fos表达阳性细胞计数及机械痛阈无显著差异。结论两种模型再生神经生长进入去神经支配区域时,均出现支配区域的痛觉超敏和疼痛相关行为,神经性疼痛程度无差异。     

鞘内注射TNP-ATP对骨癌痛大鼠机械痛敏的影响

目的 观察骨癌痛大鼠鞘内注射P2X受体抑制剂TNP-ATP后的患侧后肢机械缩足反射阈值(MWT)和双后肢负重差值变化.方法 雌性SD大鼠32只,随机分为4组(n=8):Sham组、Model组、ddH2O组和TNP-ATP组.Sham组左胫骨髓腔注射PBS液5 μl,其他3组分别注射Walker256细胞悬液5 μl(2×107个/ml).建模后5 d,所有大鼠皆鞘内置管;建模后7 d,ddH2O组鞘内注射ddH2O 10 μl,TNP-ATP组鞘内注射TNP-ATP(30 nmol)10 μl ,其余两组不进行鞘内注射.在建模前、建模后3、6、9、12 d用Von Frey丝测定大鼠患侧后肢机械缩足反射阈值,用负重仪测大鼠双后肢负重差值.结果 与Sham组比较,Model组和ddH2O组建模后第6～12 d左后肢痛觉超敏,MWT值进行性下降,双后肢负重差值进行性增加.TNP-ATP组鞘内给药后患侧后肢MWT升高,双后肢负重差值减小.结论 鞘内注射TNP-ATP能减轻但不能完全抑制大鼠胫骨癌痛引起的机械痛敏.     

中脑导水管周围灰质内神经降压素对β-内啡肽在痛行为反应中作用的影响

 为观察中脑导水管周围灰质内神经降压素对β-内啡肽在痛行为反应中作用的影响,以钾离子透入法引起大鼠甩尾反应为痛行为反应指标测定痛阈,发现大鼠中脑导水管周围灰质(PAG)内注人β-内啡肽(β-EP)后大鼠痛行为反应阈值升高.PAG内注入微量神经降压素(NT)后,可加强β-EP的镇痛效应,而注入抗神经降压素血清(ANTS)后,则降低β-EP的镇痛效应.提示,PAG内的NT和β-EP在痛行为反应的调制中有着密切关系.     

大鼠骨癌痛模型的制备及电压依赖性钠通道Nav1.8在其背根神经节的表达研究

目的 建立大鼠骨癌痛模型并观察电压依赖性钠通道Nav1.8在其背根神经节(DRG)的表达,以探讨Nav1.8在癌症性疼痛中的作用.方法 在雌性SD大鼠左胫骨内注射Walker256细胞(103/μl、104/μl、105/μl)后1、3、5、7、10、14天观察机械痛敏阈值和CO2激光热痛敏阈值的变化,与对照组大鼠进行比较,分析癌痛组大鼠出现痛阈降低的时间.于接种细胞后14天取双侧胫骨做病理切片观察肿瘤生长情况.RT-PCR检测癌痛组及对照组大鼠L5～L6DRG Nav1.8基因的表达.结果 所有接种Walker256细胞的大鼠均可见胫骨内实质性肿瘤的膨胀性生长和严重的骨质重构.各癌痛组大鼠分别于第7～14天出现进行性加重的疼痛行为学改变,其左侧(癌痛侧)DRG Nav1.8的表达明显升高(P＜0.05),对侧的表达与对照组之间无明显差异.结论 胫骨内注射Walker256细胞的大鼠在产生浸润性生长的骨肿瘤同时,可伴进行性的痛觉过敏,是骨转移瘤相关疼痛研究可靠的动物模型.Nav1.8基因在骨癌痛模型大鼠DRG中的表达水平上调,提示该通道可能参与骨癌痛的发生过程.     

大鼠皮层神经元机械性损伤模型中p75NTR、Bax、Bcl -2表达及细胞凋亡

目的 研究大鼠神经元机型性损伤后p75 NTR、Bax、Bcl -2表达改变及神经细胞凋亡情况,分别探讨其在神经元凋亡过程中的作用机制及相互作用方式. 方法 制备大鼠神经元体外培养机械性损伤模型,测定损伤后神经元细胞的凋亡率,依据不同损伤程度分为轻、中、重度损伤组和对照组,应用特异性抗体细胞免疫法检测各组别间神经元Bax、Bcl -2表达的差异.应用Western blot法检测各组间p75NTR蛋白表达水平的差异. 结果 损伤后神经元细胞的凋亡率明显高于正常对照组神经元.重度损伤组较中度损伤组和轻度损伤组显著升高(P＜0.05).机械性损伤各组均有Bax、Bcl -2的表达,且不同损伤程度组别间表达水平差异有统计学意义.重度损伤组Bax显著高于中度损伤组和轻度损伤组(P＜0.05). 结论 p75 NTR表达、Bax/Bcl -2比值与神经元凋亡密切相关.p75NTR早期表达可能是神经元损伤后细胞凋亡的因素之一,Bax、Bcl -2可能与这一过程相关.     

骨癌痛模型大鼠痛行为与脊髓星形胶质细胞活化的关系

目的 观察前列腺癌骨转移疼痛模型大鼠的痛行为学与腰段脊髓背角星形胶质细胞活化的关系.方法 雄性SD大鼠60只,随机分为3组,每组20只.A组(模型组):于胫骨骨髓腔内注射10μl前列腺癌细胞;B组[氟代柠檬酸(FCA)处理组]:建立模型后2周,鞘内单次注射氟代柠檬酸;C组(对照组):左侧后肢胫骨注射10/μl Hanks液.术后1、3、5、 7、 10、14、21d检测大鼠后肢足底机械性触诱发痛[测定大鼠足底缩爪阈值(PWT)]和热痛敏[测定大鼠对热刺激的反应潜伏期(HRL)],对部分动物进行灌流固定,取大鼠模型侧后肢胫骨,HE染色观察骨结构的破坏情况.并取脊髓L4-L6节段,采用免疫荧光组织化学法观察脊髓内星形胶质细胞的表达及活化情况.结果 C组大鼠术后各时间点机械性触诱发痛和热痛敏无显著差异;在术后的前7d,与C组大鼠相比,A、B组PWT的差异无统计学意义,第10d起A、B组大鼠的PWT低于C组.给予FCA后2d(术后第14天),B组PWT显著高于A组,但随着时间的延长,B组PWT有逐渐降低的趋势.大鼠后肢胫骨HE染色可见术后14d时A组胫骨骨小梁广泛破坏.免疫荧光组织化学染色结果显示,C组大鼠术后各时间点胶质细胞活化水平无显著差异,A组和B组大鼠在术后的前7d与C组大鼠相比无显著差异,此后A组大鼠的星形胶质细胞活化水平持续升高,而B组大鼠星形胶质细胞维持在较低的活化水平.结论 星形胶质细胞的活化水平与前列腺癌骨转移痛模型大鼠痛行为密切相关.     

Quantitative assessment of metabolic bone disease in rat models by dual tracer method

The usefulness of radionuclide techniques for early differential diagnosis of metabolic bone disease has been controversial. We tried to develop a new method to distinguish alterations in bone metabolism prior to radiologic changes, measuring 24-hr whole-body retention (WBR) and femoral uptake of two radiopharmaceuticals (47Ca-chloride, 99mTc-MDP). Control normal (C), osteoporosis (P) osteomalacia (M) and steroid-induced osteoporosis (S) were produced in 60 eight-week old Wistar male rats by means of dietary manipulation and steroid administration. Fine detail radiographs of the femurs and bone specimens were obtained over six weeks at two week intervals. Good correlation between WBR and femoral uptake of 47Ca was noted (r = 0.86, p less than 0.01). WBR ratios of 47Ca were significantly higher in the M and S groups and were lower in the P group when compared to the C group throughout the study. WBR ratios of 99mTc-MDP were significantly higher in the M group and were lower in the S group from the 2nd week. Fine detail radiographs analysis by microdensitometry revealed significant osteopenia in the S, M and P groups from the 4th week. The dual tracer method was found to distinguish alterations in bone metabolism in the groups examined prior to detectable radiologic changes.     

大麻素受体2在胫骨癌痛大鼠脊髓的表达及意义

目的探讨大麻素受体2（CB2）在胫骨癌痛大鼠脊髓的表达及其在癌痛产生和维持中的作用。方法 雌性SD大鼠42只,体重160～180g,随机分为5组：对照组（C组）、假手术组（S组）、骨癌痛组（BCP组）、DMSO（二甲基亚砜）组（D组）和CB2选择性拮抗剂AM630组（A组）。采用右侧胫骨干骺端骨髓腔内注射5μlWalker256（4×105）乳腺癌细胞制备大鼠胫骨癌痛模型,于接种后第7d从S组和BCP组分别随机选取6只,同C组的大鼠一起处死取脊髓,采用免疫印迹技术观察脊髓CB2的表达,在接种后的第1、2及第3天按照分组D组和A组分别鞘内注射DMSO0.15μl和溶于1%DMSO的AM63015μg。分别于注射肿瘤前1d、注射后的第1、3、5、7、14、21d（T0～6）测定机械痛阈和热痛阈。结果免疫印迹显示C组大鼠脊髓基本没有CB2的表达,与C组及S组相比,BCP组接种后第7d脊髓CB2表达水平升高。鞘内注射AM630癌细胞后大鼠接种后肢提前出现机械痛觉过敏现象。结论脊髓CB2参与大鼠胫骨癌痛的产生和维持。     

Therapy of metastatic bone pain.

Bone metastasis is a common sequella of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Currently, the treatment of bone pain remains palliative at best with systemic therapy (analgesics, hormones, chemotherapy, steroids, and bisphosphonates) as well as local treatments (such as surgery, nerve blocks, and external beam radiation). However, many of these treatments are limited in their efficacy or duration and have significant side effects that seriously limit the cancer patient's quality of life. Various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studies, improved survival. Additional radiopharmaceuticals are under investigation and appear promising. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment.     

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after⁸⁹Sr administration. Patients received 2 MBq/kg (118–148 MBq) of⁸⁹Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%–66% reduction in white cell count and a 14%–75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that⁸⁹Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.     

Mirror-image Artifact of a Cephalhematoma Mimicking an Epidural Hematoma in a Newborn

Teaching Point: When performing ultrasound examination of a cephalhematoma, the occurrence of a mirror-image artifact can mimic the presence of an epidural hematoma.     

Magnetic field distribution in models of trabecular bone

A magnetostatic model consisting of a tetragonal lattice of struts of diamagnetic material, mimicking vertebral trabecular bone, was developed. The model allows estimation of the magnetic field histogram within the lattice's unit cell as a function of geometric parameters. The field was computed analytically from the induced magnetic surface charge density on the faces of the struts. The contribution from the induced magnetic field to the effective transverse relaxation rate, R₂ was obtained as the mean decay rate of the Fourier transformed histograms, for both fixed and randomly oriented lattices. The model predicts the field distribution to increase with both strut thickness and density, paralleling material density. Finally, significant changes in R₂′ are predicted at constant material density, in that the field distribution widens with simultaneously increasing strut number density and decreasing strut thickness.