MiR-139-3p通过靶向下调TRPV1缓解大鼠神经病理性疼痛

目的:研究miR-139-3p在大鼠神经病理性疼痛发生发展中的作用及其作用机制。方法:将大鼠随机分为假手术组(sham)、坐骨神经慢性压迫损伤模型组(chronic constriction injury group,CCI)、2 mg/kg miR-139-3p模拟物(mimic)鞘内注射组、4 mg/kg miR-139-3p mimic鞘内注射组。术后的第14 d,Real-time PCR法检测大鼠背根神经节(DRG)中miR-139-3p及TRPV1的表达。于注射前及注射后的第1、3、7、14 d,利用von Frey检测大鼠机械性痛阈及热辐射法检测大鼠热痛阈值。Western Blot法检测DRG中TRPV1的表达;ELISA法检测脊髓L4-L5组织中TNF-α及IL-1β的含量;双荧光素酶报告基因法检测miR-139-3p与TRPV1的靶向关系。结果:(1)与sham组相比较,miR-139-3p在CCI大鼠DRG中的表达显著下降,而TRPV1的表达显著上升(P0.05)。(2)与sham组相比较,CCI组中大鼠机械刺激缩足反射阈值及热刺激缩足反射潜伏期显著下降(P0.05);而与CCI组相比较,鞘内注射miR-139-3p mimic可显著促进大鼠机械刺激缩足反射阈值及热刺激缩足反射潜伏期的上升,抑制TRPV1的表达(P0.05)。(3)与sham组相比较,CCI组大鼠TNF-α及IL-1β含量显著上升(P0.05);而与CCI组相比较,鞘内注射miR-139-3p mimic可显著抑制TNF-α及IL-1β的产生(P0.05)。(4)miR-139-3p mimic转染可显著降低荧光素酶报告基因的荧光强度。结论:miR-139-3p通过靶向下调TRPV1的表达缓解大鼠神经病理性疼痛。     

丙戊酸钠减轻博莱霉素致大鼠肺纤维化

目的:探讨丙戊酸钠在博莱霉素诱导的肺纤维化中的作用及机制。方法:42只大鼠随机分为正常对照组、模型组和治疗组。造模采用博来霉素5 mg/kg气管内注射,自造模14 d开始分别采用生理盐水(0.5m L/d)、丙戊酸钠(300 mg·kg-1·d-1)和地塞米松(0.6 mg·kg-1·d-1)腹腔内注射治疗14 d。模型组分别在造模后14和、28 d处死。治疗组在造模后28 d处死。然后通过HE染色、Masson染色、羟脯氨酸(HYP)检测和Western blotting检测α-平滑肌肌动蛋白(α-SMA)及E-钙黏蛋白(E-cadherin)表达的变化,综合分析丙戊酸钠对肺纤维化发展的干预作用。结果:HE染色显示丙戊酸钠治疗组的肺泡结构、肺间质的形态优于生理盐水组和地塞米松治疗组。Masson染色及HYP检测用于衡量肺组织内胶原的分布及含量,可见丙戊酸钠治疗组肺组织内胶原的分布及含量均显著低于地塞米松治疗组及生理盐水组。丙戊酸钠可以降低α-SMA的表达,同时上调上皮标志性蛋白E-cadherin的表达。结论:丙戊酸钠可以通过减少胶原的表达与分布及下调间充质蛋白α-SMA,同时上调上皮蛋白E-cadherin的表达从而减轻博来霉素诱导大鼠肺纤维化。     

环巴明抑制SHH信号通路缓解大鼠神经病理性疼痛

目的拟探讨环巴明抑制SHH信号通路对坐骨神经分支选择性损伤(SNI)大鼠的痛敏改变及脊髓水平BDNF、NR2B变化的影响。方法将大鼠随机分为对照组(control组)、坐骨神经分支选择性损伤组(SNI组)、溶剂对照组(SNI-vehicle组)和环巴明组(SNI-CP组),各组12只。分别于建模前1 d、建模后1和7 d测定机械缩足反应阈(PMWT)。于建模后7 d行为学测量后处死大鼠取L4-6脊髓组织,用Western blot法及实时荧光定量PCR法测定脊髓组织SHH、GLI1及BDNF表达,用免疫组化法测定脊髓组织NR2B蛋白表达。结果与对照组相比,SNI组、SNI-vehicle组和SNI-CP组PMWT均降低,脊髓组织SHH、GLI1及BDNF蛋白及mRNA表达均上调,且脊髓组织NR2B表达亦上调(P0.05);但与SNI组相比,SNI-CP组经环巴明处理后PMWT升高,且脊髓组织SHH、GLI1及BDNF表达下调,脊髓组织NR2B表达亦下调(P0.05)。结论环巴明抑制SHH信号通路能改善SNI大鼠神经病理性疼痛,其机制可能与其调节脊髓水平BDNF和NR2B蛋白表达有关。     

丙戊酸钠在精神科临床中的应用

目的：了解丙戊酸钠在临床上的治疗效果。方法选取我院在2013年1月~2014年1月这1年时间内收治的精神科患者共160例,随机分为对照组及观察组,每组80例。对照组采用常规模式治疗,观察组采用丙戊酸钠药物治疗。统计患者使用药物后的不良反应情况,了解这类药物临床应用于不同精神疾病的作用。结果丙戊酸钠能够有效缓解患者不同精神疾病症状,减轻躁动、抑郁等不良情绪的程度,但临床使用中易出现头晕头痛、血小板减少、胃肠道不适等不良反应。结论丙戊酸钠对于精神科患者而言临床效果较好,能够减轻患者精神疾病程度,但使用时应注意对患者不良反应的预防与治疗,提升临床用药有效性。     

神经病理性疼痛的免疫机制

研究发现,在中枢神经系统及外周神经系统中,免疫细胞和分子在神经病理性疼痛过程中发挥着越来越重要的作用,对传统的以神经元为中心的疼痛理论发起了挑战。神经损伤后外周的肥大细胞、中性粒细胞、巨噬细胞和T淋巴细胞等免疫细胞所产生的级联炎性反应以及胶质细胞的激活是神经病理性疼痛形成和维持的关键因素,这些免疫细胞通过释放大量炎性介质最终导致疼痛的产生。     

GDF10在神经病理性疼痛大鼠脊髓中的表达

目的:观察生长和分化因子10(GDF10)在神经病理性疼痛大鼠脊髓中的表达变化。方法:取雄性SD大鼠60只,通过结扎左侧L5脊神经制备神经病理性疼痛模型,于术前1 d,术后当天及术后1 d、3 d、10 d、21d检测大鼠左后爪50%缩爪阈值,并采用免疫荧光染色及Western blot检测大鼠L5脊髓后角GDF10的表达变化。结果:脊神经结扎大鼠在术后1 d缩爪阈值开始降低,自3 d起,与正常对照组相比差异有统计学意义(P0.05),到10 d阈值下降最明显,至21 d呈现持平状态。免疫荧光检测观察到伤侧L5脊髓组织中GDF10主要表达于脊髓背角神经元细胞的胞浆内。GDF10在术后持续降低,到10 d降低最为显著,与正常组相比差异具有统计学意义(P0.05),一直持续低水平表达至21 d。Western blot证实术后10 d脊髓中GDF10蛋白的表达较正常组大鼠明显降低(P0.05)。结论:大鼠脊神经结扎使脊髓背角中GDF10表达减少,其减少可能与大鼠脊神经损伤后对机械刺激引起的疼痛过敏有关联。     

安定、丙戊酸钠及拉莫三嗪对实验大鼠癫癎持续状态作用的研究

目的：研究安定、丙戊酸钠及拉莫三嗪对实验大鼠癫癎持续状态的治疗作用。方法：采用氯化锂-匹罗卡品癫癎持续状态鼠模型，癫癎持续状态2h后，分别给予上述三种抗癫癎药物治疗，观察比较癫癎持续状态的时间。结果：三种抗癫癎药物对癫癎持续状态有不同程度的控制作用，安定起效最为迅速，丙戊酸钠次之，拉莫三嗪较慢，但安定对意识状态有影响。结论：癫癎持续状态的治疗，安定仍然是首选，但丙戊酸钠及拉莫三嗪亦是有效的药物，早期联合长效抗癫癎药物治疗可能是最佳的选择。     

神经病理性疼痛及其发病机制的研究进展

<正>神经病理性疼痛(neuropathic pain)的特点是致病因素和临床表现的多样化,所造成痛苦轻重不一,差别很大,直接或间接造成神经系统损害[1-3]。IASP官方学术期刊Pain在2011年首期发表了由21家单位署名的NeuPSIG神经病理性痛评价纲要一文中指出,神经病理性痛是由躯体感觉神经系统的损伤或疾病而直接造成的疼痛(pain arising as a direct consequence of a lesion or disease affecting the somatosensory system)。神经病理性疼痛是周围或中枢神经系统原发性或继发性损害或功能障碍或短暂紊乱引起的疼痛(IASP,1994)。作为世界性难题的神经病理性疼痛,全世界患病人     

帕罗西汀合并丙戊酸钠治疗伴有焦虑的抑郁症对照研究

抗抑郁药5-羟色胺冉摄取抑制剂（SSRIs）在临床上已被广泛应用，具有良好的疗效，但是起效较慢，早期不良反应明显，且患者长期应用具有转躁的可能性㈦。心境稳定剂，如卡马西平．丙戊酸钠等，具有稳定患者的激越情绪、改善睡眠障碍的作用。本研究采用丙戊酸钠缓释剂与帕罗两汀早期联合的方法，观察是否可以弥补SSRIs类药物的上述不足。     

不同剂量丙戊酸钠预防治疗偏头痛疗效比较

丙戊酸钠是治疗癫痫的有效药物,作者在1997年开始对29例严重偏头痛患者用丙戊酸钠作预防性治疗组,其中15例为日剂量组,14例为周剂量组.同时对15例口服苯噻啶作对照组,经观察比较,日剂量组的总有效率为92.8%,周剂量组的总有效率为86.6%.对照组的总有效率为73.3%,日剂量组与对照组间统计学处理有显著差异(p<0.05).     

Role of spinal cholecystokinin in neuropathic pain after spinal cord hemisection in rats

In the present study we determined whether spinal cholecystokinin (CCK) or the cholecystokinin receptor is involved in below-level neuropathic pain of spinal cord injury (SCI). The effect of the CCK_B receptor antagonist, CI-988 on mechanical allodynia and the expression level of CCK and CCK_B receptor were investigated. Spinal hemisection was done at the T13 level in rats under enflurane anesthesia. CI-988 was administered intraperitoneally and intrathecally and behavioral tests were conducted. After systemic injection, mechanical allodynia was reduced by higher doses of CI-988 (10 and 20 mg/kg). Intrathecal CI-988 (100, 200 and 500 μg) dose-dependently increased the paw withdrawal threshold in both paws. Following spinal hemisection, CCK mRNA expression increased on the ipsilateral side at the spinal segments caudal to the injury and both sides of the spinal L4-5 segments without any significant changes in CCK_B receptor mRNA levels. These results suggest that up-regulation of spinal CCK may contribute to maintenance of mechanical allodynia following SCI and that clinical application of CI-988 or similar drugs may be useful therapeutic agents for management of central neuropathic pain.     

Spinal cord stimulation induces c-Fos expression in the dorsal horn in rats with neuropathic pain after partial sciatic nerve injury

Spinal cord stimulation (SCS) is an established treatment for intractable neuropathic pain, especially CRPS-1. The mechanisms of action of SCS have only been partly elucidated and include suppression of the hyper-excitability of the Wide Dynamic Range neurons and a GABA increase in the dorsal horn. In the present study we demonstrate an increase of c-Fos immunoreactive cells in the dorsal horn after SCS, suggesting early cellular activation that may preclude earlier described electrophysiological and biochemical changes in the dorsal horn after SCS. In a rat model of neuropathic pain, allodynia was induced and quantified using the von Frey test. In 11 rats a SCS device was implanted and spinal cord stimulation performed. Withdrawal threshold were measured every 15 min up to 90 min. A sham group (n = 6) also had a SCS device implanted, but did not receive SCS. After SCS the animals were perfused and histology was performed for quantification of c-Fos immunoreactivity in the dorsal horns. We found a significant increase in c-Fos in the SCS group compared to our sham group and control tissue, indicating late cellular activity in the dorsal horn after SCS.     

Repeated administration of systemic gabapentin alleviates allodynia-like behaviors in spinally injured rats

The effect of systemic gabapentin, a novel antiepileptic and analgesic, was tested on allodynia-like behaviors in spinal cord injured rats. On the first day of treatment 30 mg/kg intraperitoneal gabapentin did not alleviate hyper-reactivity to mechanical and cold stimulation. The allodynia was significantly reduced by 100 mg/kg gabapentin, which however, produced sedation and motor impairments. Repeated administration of 30 mg/kg gabapentin once a day produced a gradually increasing anti-allodynic effect. Total alleviation of mechanical allodynia was observed in most rats after the third administration of gabapentin. Thus, build-up of the antiallodynic effect of gabapentin may develop through a time dependent mechanism or alternatively through a gradual accumulation of the effective central nervous system concentration of the drug.     

JNK/MCP-1信号通路在姜黄素抗糖尿病神经病理性疼痛中的作用

 目的:观察JNK/MCP-1通路在姜黄素抗大鼠糖尿病神经病理性疼痛（DNP）中的作用及机制。方法:雄性SD大鼠诱导为2型糖尿病神经病理性痛大鼠（DNP）模型,将其随机分为6组（n=27）： DNP组、姜黄素组（Cur组）、溶剂对照组（DSC组）、JNK抑制剂组 (DJ组)、JNK抑制剂溶剂对照组(DJS组)、姜黄素+单核细胞趋化蛋白 1 (MCP-1)激动剂组（DM组）。另取27只正常大鼠为正常对照组（C组）,给药后3 d、7 d、14 d时测定机械缩足痛阈和热缩足潜伏期,并在同一时点取脊髓腰膨大及L4~6背根神经节（DRG）,用免疫印迹法测定脊髓和DRG中p-JNK水平,用ELISA测定脊髓和DRG中的MCP-1含量。结果:与DNP组相比,在给药后的7 d、14 d Cur组、DJ组、DM组p-JNK的表达明显下降（P<0.05）;与C组相比,链脲佐菌素给药后其它6组MCP-1含量出现明显下降;与DNP组相比,在给药后的7 d、14 d Cur组、DJ组MCP-1出现明显上升,而DM组出现进一步下降（P<0.05）。结论: DNP大鼠脊髓和DRG中的p-JNK、MCP-1表达明显升高,姜黄素减轻2型糖尿病大鼠神经病理性疼痛的机制可能与JNK/MCP-1信号通路有关。     

Antiallodynic effects of acupuncture in neuropathic rats

Peripheral nerve injury often results in abnormal neuropathic pain such as allodynia or hyperalgesia. Acupuncture, a traditional Oriental medicine, has been used to relieve pain and related symptoms. However, the efficiency of acupuncture in relieving neuropathic pain is not clear. The aim of this study was to investigate the anti-allodynic effects of acupuncture through behavioral and electrophysiological examinations. Male Sprague-Dawley rats were subjected to neuropathic surgery consisting of a tight ligation and transection of the left tibial and sural nerves, under pentobarbital anesthesia. The acupuncture experiment consisted of four different groups, one treated at each of three different acupoints (Zusanli (ST36), Yinlingquan (SP9), and a sham-acupoint) and a control group. Behavioral tests for mechanical allodynia and cold allodynia were performed for up to two weeks postoperatively. Extracellular electrophysiological recordings were made from the dorsal roots using platinum wire electrodes. Mechanical and cold allodynia were significantly reduced after acupuncture treatment at the Zusanli and Yinlingquan acupoints, respectively. Electrophysiological neural responses to von Frey and acetone tests were also reduced after acupuncture at the same two acupoints. These results suggest that acupuncture may be beneficial in relieving neuropathic pain.     

Effects of clonidine on bilateral pain behaviors and inflammatory response in rats under the state of neuropathic pain

This study was conducted to investigate the effects of clonidine on bilateral pain behaviors and inflammatory responses in neuropathic pain induced by partial sciatic nerve ligation (PSNL), and to better understand whether the antinociception of clonidine was related to α₂-adrenoceptor mechanisms. Rats were divided randomly into five groups: sham-operation with saline, i.p.; PSNL with clonidine (0.2 mg/kg) or saline, i.p.; PSNL with yohimbine (2 mg/kg) followed by clonidine (0.2 mg/kg), i.p.; and PSNL with naloxone (0.3 mg/kg) followed by clonidine (0.2 mg/kg), i.p. On post-operative days 1, 3, 7, 14, and 21, both ipsilateral and contralateral pain behaviors were measured. In rats receiving antagonists, bilateral behavioral changes were measured on day 14. Bilateral paw pressure threshold and paw withdrawal latencies were measured, and the extent of glial activation was dertermined by measuring macrophage antigen complex-1 (Mac-1) and glial fibrillary acidic protein (GFAP). Additionally, the levels of tumor necrosis factor α (TNF-α) and interleukin (IL)-6 were determined. PSNL induced bilateral behavioral hyperalgesia, with the ipsilateral level displaying a higher extent of behavior changes than the contralateral side. In addition, the glial activation markers and cytokine production were augmented bilaterally. Clonidine caused significant attenuation of bilateral mechanical allodynia and thermal hyperalgesia, accompanied by inhibition of glial activation and the expression of cytokines. The effects of clonidine were blocked by the α₂-adrenoceptor antagonist yohimbine and partially reversed by the μ-opioid receptor antagonist naloxone. These data suggest that the bilateral antinoceptive effects of clonidine might mediate through immunomodulation by acting on α₂-adrenoceptor in rats undergoing neuropathic pain.     

基于LC-MS的紫杉醇以及奥沙利铂致神经病理性疼痛大鼠脊髓背角代谢组分析

目的 从代谢组学的角度探讨紫杉醇和奥沙利铂两种经典化疗药物的致神经病理性疼痛机制.方法 清洁级成年雄性Sprague Dawley(SD)大鼠随机分成3组:生理盐水组(S组)11只、奥沙利铂组(0组)15只和紫杉醇组(P组)19只,取大鼠模型脊髓背角用液相色谱-质谱联用技术(LC-MS)进行代谢组学检测并分析代谢组变化...     

Local expression of inducible nitric oxide synthase in an animal model of neuropathic pain

Peripheral nerve injury is associated with local inflammation and neuropathic pain. In this study we investigated the local expression of the inducible isoform of nitric oxide synthase (iNOS) following a chronic constriction injury (CCI) to the sciatic nerve, a rat model of neuropathic pain. Western blot analysis and immunohistochemical co-localization methods were used to identify temporal and spatial expression of iNOS and its cells of origin. Changes in mRNA were analyzed by RT-PCR and iNOS specific primers. We report that CCI injury induced local iNOS expression in both macrophages and Schwann cells within and distal to the injury site. The local increase in iNOS mRNA expression paralleled both the temporal and spatial protein expression. This study supports the hypothesis that CCI is associated with a local inflammatory reaction mediated at least in part by iNOS. Local activation of the iNOS-NO system may play an important role in the pathogenesis of peripheral nerve injury and neuropathic pain.