芒果苷对CCI大鼠神经病理性疼痛的改善作用北大核心CSCD

目的:探究芒果苷对慢性缩窄性损伤(CCI)大鼠神经病理性疼痛的作用及机制。方法:采用成年SpragueDawley大鼠构建CCI模型,以模拟临床神经病理性疼痛。将大鼠随机分为假手术组(Sham组)、CCI组、CCI+Man组[手术后立即用40 mg/(kg·d)芒果苷灌胃,连续治疗17 d],10只/组。术后连续17 d观察缩爪机械阈值(PWMT)和缩爪热潜伏期(PWTL);术后17 d,处死大鼠,ELISA检测脊髓中细胞因子IL-1β、IL-6及趋化因子CCL2、CCR2表达水平;免疫荧光法检测脊髓神经元中Cleaved caspase-3和pJNK蛋白表达水平;免疫组化法和Western blot分析脊髓中c-Fos蛋白表达水平。结果:与Sham组相比,CCI组大鼠术后第1~17天的PWMT和PWTL显著降低,脊髓中促炎因子IL-6、IL-1β,趋化因子CCL2、CCR2及c-Fos蛋白水平明显升高(P<0.001);脊髓神经元细胞中Cleaved caspase-3和pJNK蛋白水平明显升高(P<0.001)。经芒果苷治疗后,CCI组大鼠术后第1~17天的PWMT和PWTL显著升高,脊髓中促炎因子IL-6、IL-1β,趋化因子CCL2、CCR2及c-Fos蛋白水平明显降低(P<0.01);脊髓神经元细胞中Cleaved caspase-3和pJNK蛋白水平明显降低(P<0.01)。结论:芒果苷对CCI大鼠的神经病理性疼痛具有改善作用,其可能与降低脊髓炎症、凋亡、c-Fos及pJNK蛋白表达有关。     

TRPM2在损伤性神经性疼痛过程中参与急性疼痛向慢性疼痛的转化

目的 探究TRPM2在损伤性神经性疼痛中的作用和可能机制.方法 建立坐骨神经慢性缩窄性损伤(CCI)大鼠模型,体外培养原代背根神经节(DRG)细胞并完成siRNA的转染,CCI大鼠早期(CCI术后1～4 d)或晚期(CCI术后7～10 d)每天给予阴性对照或siTRPM2处理.RT-PCR检测CCI大鼠DRG和脊髓中TRPM2 mRNA的表达,观察大鼠机械痛敏感性和热痛敏感性情况,测定iNOS、NO和ROS水平.结果 CCI显著增加DRG和脊髓中TRPM2的表达,CCI术后早期敲除TRPM2可减轻损伤引起的神经性疼痛,而后期敲除则没有效果,CCI大鼠敲除TRPM2可显著降低iNOS的表达、NO以及ROS的水平.结论 TRPM2主要参与损伤性神经性疼痛中急性疼痛向慢性疼痛的早期转化,其减轻了早期阶段损伤引起的神经性疼痛,这是一个潜在的神经性疼痛的早期治疗靶点.     

内质网应激特有的caspase-12在神经病理性疼痛大鼠脊髓背角的表达

目的:检测内质网应激特有caspase-12凋亡途径与神经病理性疼痛模型大鼠脊髓背角神经元凋亡之间的关系。方法:SD雄性大鼠随机分为假手术组(sham)和坐骨神经慢性压迫(CCI)模型组。检测大鼠在手术前及术后21 d的热痛敏和机械痛敏;CCI术后21 d,免疫组织化学检测大鼠脊髓背角内葡萄糖调节蛋白78(GRP78)、caspase-12和caspase-3的表达;TUNEL法检测脊髓背角内细胞的凋亡。结果:与假手术组相比,模型组的热痛敏和机械痛敏在术后均明显下降,脊髓背角内GRP78、caspase-12和caspase-3的表达均增高,凋亡染色阳性细胞数目也较多。结论:坐骨神经慢性压迫模型大鼠脊髓背角内神经元凋亡的途径之一是内质网应激特有caspase-12介导的,可能与神经病理性疼痛的发生、发展有关。     

内质网应激介导的JNK通路在大鼠神经病理性疼痛中的作用

目的:检测内质网应激介导的JNK通路在坐骨神经慢性压迫(CCI)模型大鼠中的作用。方法:SD雄性大鼠随机分为假手术组(sham)和模型组(CCI)。CCI前、后1、3、5、7、14 d测定大鼠的热痛敏和机械痛敏;CCI后14 d,免疫组织化学检测大鼠脊髓背角内葡萄糖调节蛋白78(GRP78)、p-JNK、caspase-3和胶质纤维酸性蛋白(GFAP)的表达;TUNEL法检测脊髓背角内的细胞凋亡。结果:与假手术组相比,模型组的热痛敏和机械痛敏在术后均明显下降,脊髓背角内GRP78、p-JNK、caspase-3和GFAP的表达均增高,凋亡染色阳性细胞数目也较多。结论:内质网应激介导的p-JNK途径参与了神经病理性疼痛模型大鼠脊髓背角内神经元凋亡,可能与星形胶质细胞的活化有关。     

辛伐他汀对大鼠坐骨神经慢性压迫性损伤模型氧化应激和炎症的影响

目的探讨辛伐他汀对大鼠坐骨神经慢性压迫性损伤(CCI)模型疼痛及氧化应激和炎症的影响。方法 50只雄性SD大鼠随机分为5组:假手术组+口服灌胃生理盐水组、CCI模型组+口服灌胃生理盐水组、CCI模型+辛伐他汀灌胃(15 mg·kg~(-1)·d~(-1))组、CCI模型+辛伐他汀灌胃(30 mg·kg~(-1)·d~(-1))组,每组10只。术前1 d及术后7 d和14 d观察辛伐他汀灌胃对大鼠患侧热缩足反射潜伏期(TWL)和机械缩足反射阈值(MWT)的影响,第14 d取各组大鼠右侧坐骨神经,检测氧化应激和炎症相关因子的变化情况。结果与假手术组+生理盐水灌胃组相比较,CCI模型+生理盐水灌胃组TWL和MWT显著下降(P<0.05);与CCI模型+生理盐水灌胃组相比较,辛伐他汀灌胃7 d和14 d后,TWL和MWT明显升高(P<0.05)。另外,辛伐他汀灌胃还抑制了CCI损伤引起的氧化应激和炎症反应。结论辛伐他汀灌胃通过抑制氧化应激和炎症反应缓解了神经病理性疼痛。     

阿利吉仑对慢性坐骨神经缩窄性损伤大鼠TNF-α表达的影响

目的探讨阿利吉仑对慢性坐骨神经缩窄性损伤(CCI)大鼠模型热痛阈和机械痛阈表达和肿瘤坏死因子-α(TNF-α)表达的影响。方法通过在坐骨神经上结扎四个松结制备实验CCI大鼠模型,大鼠随机分为正常组、CCI组和阿利吉仑组(50 mg/kg,腹腔注射)。造模后14 d检测各组热痛阈和机械痛阈,实时荧光定量PCR检测坐骨神经TNF-αmRNA表达。结果与正常组比较,模型组和阿利吉仑组热痛阈和机械痛阈显著降低,TNF-αmRNA表达水平显著增高(0.01)。与模型组比较,阿利吉仑组坐骨神经热痛阈、机械痛阈显著增高,TNF-αmRNA表达水平显著降低(0.01)。结论阿利吉仑上调坐骨神经缩窄性损伤大鼠坐骨神经热痛阈和机械痛阈可能与下调TNF-αmRNA表达相关。     

曲尼司特对CsA慢性肾毒性大鼠TGF-β/Smad通路的影响

目的 探讨不同剂量曲尼司特(TNL)对环孢素A(CsA)慢性肾毒性大鼠肾脏彻TGF-β/Smad通路的的影响.方法 雄性SD大鼠34只,随机分成正常对照组、模型组、TNL低剂量治疗组、TNL中剂量治疗组、TNL高剂量治疗组、安博维治疗组.采用低盐饮食加CsA 20 mg/(kg·d)灌胃的方法建立环孢素A慢性肾毒性大鼠模型.用RT-PCR和免疫组织化学检测不同剂量TNL对大鼠肾脏TGF-β1、Snad3、Smad7的影响.结果 TNL能下调CsA慢性肾毒性大鼠肾组织中TGF-β1、Smad3的mRNA水平及在肾脏的表达,上调Smad7的mRNA水平及在肾脏的表达.结论在CsA慢性肾毒性大鼠模型中,TNL可能通过调节TGF-β/Smad通路而发挥抗纤维化的作用,从而减缓CsA慢性肾毒性的进展.     

鞘内注射p38MAPK抑制剂SB203580对CCI大鼠脊髓背角多种嘌呤受体表达的影响

目的:观察鞘内注射p38MAPK磷酸化抑制剂SB203580对慢性坐骨神经结扎(chronic constriction injury,CCI)大鼠热痛阈及脊髓背角P2X_4、P2X_7、P2Y_(12)、P2Y_(13)受体mRNA表达变化的影响。方法:成年SD大鼠随机分为5组(n=8):假手术组(sham组)、CCI模型组(CCI+鞘内注射0.005%DMSO生理盐水)、CCI+鞘内注射SB203580 1μmol/L组、CCI+鞘内注射SB203580 10μmol/L组、CCI+鞘内注射SB203580 50μmol/L组。CCI模型组及CCI+SB203580处理组大鼠均于鞘内置管7 d后行慢性坐骨神经结扎,连续14 d鞘内注射0.005%DMSO生理盐水或SB203580(1,10,50μmol/L),2次/d,分别在术前1 d、术后第1,3,5,7,10,14 d测定给药1 h后热缩足潜伏期(TWL);并在第3,7,14 d取大鼠脊髓背角进行荧光定量PCR,观察脊髓背角P2X_4、P2X_7、P2Y_(12)、P2Y_(13)受体mRNA的表达变化。结果:CCI术后大鼠即形成稳定的热痛敏,与sham组相比,CCI模型组大鼠术后TWL明显缩短(P0.05);与CCI模型组相比,CCI+SB203580 10,50μmol/L处理组大鼠随药物剂量增加,TWL延长更为明显(P0.05)。荧光定量PCR结果显示:与sham组相比,CCI模型组第3,7,14 d,P2X_4、P2X_7、P2Y_(12)、P2Y_(13)受体mRNA的表达上调(P0.05);给予SB203580 50μmoL/L后,大鼠脊髓背角P2X_7、P2Y_(13)受体mRNA表达有所下调(P0.05),但P2X_4和P2Y_(12)受体mRNA表达没有明显变化。结论:鞘内注射p38MAPK磷酸化抑制剂SB203580可以明显抑制CCI大鼠热痛敏行为学表现,其机制与抑制脊髓背角P2X_7、P2Y_(13)受体mRNA表达有关。这提示脊髓背角小胶质细胞p38MAPK活化后上调P2X_7和P2Y_(13)受体基因转录水平可能是p38MAPK在脊髓水平参与伤害性信息传递的机制之一。     

鞘内注射丹参酮ⅡA对坐骨神经慢性压迫大鼠脊髓背角c-fos表达的影响

目的研究丹参酮ⅡA对坐骨神经慢性压迫大鼠脊髓背角内c-fos蛋白的表达,探讨丹参酮ⅡA(TanshinoneⅡA,TSA)的镇痛机制。方法 30只SD雄性大鼠随机分为假手术组(sham组,n=10)和模型组(n=20)。模型组又分为生理盐水组(NS组)和处理组(TSA组,n=10)。模型组在手术当日及术后每日在模型大鼠鞘内注射生理盐水0.1 m L和丹参酮ⅡA20 mg/kg,连续注射14 d。检测各组大鼠在手术前及术后14 d的机械痛阈和热痛阈;术后第14天,免疫组织化学法检测大鼠脊髓背角内c-fos的表达。结果与假手术组比较,生理盐水组大鼠的机械痛阈和热痛阈明显降低,c-fos的表达增多;与生理盐水组比较,处理组的机械痛阈和热痛阈明显升高,脊髓背角内c-fos的表达下降,差异均有明显统计学意义。结论鞘内注射丹参酮ⅡA对坐骨神经慢性压迫模型大鼠的镇痛作用可能与降低脊髓背角内c-fos的表达有关。     

脂肪源性干细胞移植对大鼠慢性坐骨神经缩窄性损伤IL-10和IL-1β表达的影响

目的探讨脂肪源性干细胞(ADSCs)移植对慢性坐骨神经缩窄性损伤(CCI)大鼠热痛阈和机械痛阈表达及坐骨神经中白介素-10(IL-10)和白介素-1β(IL-1β)表达的影响。方法通过在坐骨神经上结扎四个松结制备实验CCI大鼠模型,大鼠随机分为正常组、模型组和ADSCs组。ADSCs组尾静脉注射ADSCs细胞悬液,造模后14 d检测各组热痛阈和机械痛阈,实时荧光定量PCR检测坐骨神经IL-10和IL-1βm RNA表达。结果与正常组比较,模型组、ADSCs组热痛阈和机械痛阈显著降低,IL-10和IL-1βm RNA表达显著增高(0.01)。与模型组比较,ADSC组坐骨神经热痛阈、机械痛阈、IL-10 m RNA显著增高,IL-1βm RNA表达显著降低(0.01)。结论脂肪源性干细胞移植降低CCI神经性疼痛可能与调节CCI大鼠模型坐骨神经IL-10和IL-1β等抗炎症因子和前炎症因子的表达,上调热痛阈和机械痛阈相关。     

穴位电针对慢性神经病理性疼痛大鼠脊髓前列腺酸性磷酸酶表达的影响

目的 观察电针对神经病理性痛大鼠脊髓前列腺酸性磷酸酶（PAP）的表达,及腺苷含量及大鼠痛阈变化的影响,探讨电针镇痛机制。方法 21只雄性SD大鼠采用慢性坐骨神经压缩模型(CCI),取“足三里”及“太冲”穴。设假手术组（sham组）、模型组(CCI组）和电针治疗组（EA组）。采用行为学检测大鼠术前、术后第7天和电针治疗后大鼠机械痛敏值和热敏痛阈值变化,采用Real-time PCR技术检测脊髓PAP mRNA的表达,高效液相色谱法检测脊髓腺苷含量。结果 相比CCI组大鼠,电针组大鼠机械痛敏值和热敏痛阈值明显提高（P<0.05, P<0.05）。电针组大鼠脊髓PAP mRNA表达和腺苷含量比CCI组大鼠显著增加（P<0.05）。与CCI组大鼠相比,电针组大鼠脊髓腺苷含量增加（P<0.01）。结论 电针可提高神经病理性痛大鼠机械痛阈值和热敏痛阈值,其机制可能是通过增加脊髓PAP mRNA的表达和腺苷含量发挥作用。     

慢性压迫性神经损伤大鼠中透明质酸合成变化及其在神经源性疼痛中的作用

慢性神经源性疼痛由于其发病机制尚不完全明确,目前还没有十分有效的治疗手段;神经损伤后炎症反应和免疫调节机制在疼痛的发生中发挥着重要作用,透明质酸(HA)近来被认为是炎症和免疫调节中一个重要的调节分子。为了进一步研究HA是否参与到神经损伤后的病理过程中,我们检测了慢性压迫性神经损伤(CC I)大鼠损伤神经的HA含量。结果显示:与正常神经比较,HA的含量在损伤后7 d明显增加,HA合成酶(HAS)的表达也明显上调。4-甲基伞形酮(4-MU)是HAS的一种抑制剂,我们通过给予4-MU抑制HA的合成,研究HA在慢性神经源性疼痛中的作用,发现给药组CC I大鼠损伤足对热痛刺激的敏感性低于未给药组,同时IL-1β的表达量低于未给药组。以上结果提示HA可能通过对炎症因子的调控参与到损伤后的疼痛机制中,这一结果将有助于慢性神经源性疼痛的治疗。     

The anterior cingulate cortex projection to the dorsomedial striatum modulates hyperalgesia in a chronic constriction injury mouse model

IntroductionThe aim of the study was to study the role of the anterior cingulate cortex (ACC)-dorsal midbrain striatum (DMS) in neuropathic pain in mice.Material and methodsOptogenetics has been increasingly used in neuroscience research to selectively and precisely control the activity of a defined group of central neurons to determine their roles in behavioral functions in animals. The most important opsins are blue-sensitive ChR2 and yellow-sensitive NpHR. Calcium-calmodulin dependent protein kinase Iiα (CaMKIIα) is mostly expressed in the pyramidal excitatory neurons. Mice were injected with AAV2/9-CamKII-ChR2-mCherry, AAV2/9-CamKII-eNpHR3.0-GFP or AAV2/9-CamKII-mCherry virus in the ACC region, and the optical fiber implantation was performed in the ACC or DMS region. Mice were then followed up for 2 to 8 weeks and behavioral tests were carried out in the presence or absence of the blue/yellow light (473 nm/589 nm). Pain behavioral tests with or without the blue/yellow light at the same time were performed on the third and the seventh day after the chronic constriction injury of sciatic nerve model (CCI) was established. The pain thresholds of left and right hind limbs of mice in all groups were measured.ResultsNo matter whether activating the neurons in ACC or DMS, compared with normal mice in the ChR2-off-right group, and the mCherry-on-right group, the thermal pain threshold and mechanical pain threshold of the normal mice in the ChR2-on-right group were significantly lower. When inhibiting the neurons in the ACC or DMS, on day 3 and day 7 after CCI operation, the thermal pain threshold and mechanical pain threshold of the CCI mice of the NpHR-on-right group were significantly higher compared with the NpHR-off-right and mCherry-on-right groups.ConclusionsThe anterior cingulate cortex-dorsal midbrain striatum may be involved in the regulation of neuropathic pain in mice.     

1,8-桉叶素对背根神经节内P2X3受体介导神经病理痛的作用

目的:探讨1,8-桉叶素对大鼠背根神经节(DRG)神经元P2X3受体介导神经病理痛的作用。方法:建立大鼠坐骨神经慢性压迫性损伤模型(CCI)。SD大鼠随机分为假手术(Sham)组,坐骨神经慢性压迫性损伤(模型组,CCI)组、低剂量1,8-桉叶素治疗组、高剂量1,8-桉叶素治疗组、二甲亚砜对照组。检测大鼠术后7、14 d机械缩足反射(MWT)及热缩足反射潜伏期(TWL),观察大鼠行为学变化。免疫组织化学和原位杂交观察神经病理痛大鼠第4~5腰(L_(4-5))DRG神经元P2X3受体表达变化。结果:术后第7和14天,模型组大鼠MWT和TWL明显低于假手术组,低、高剂量治疗组较模型组明显升高,二甲亚砜组与模型组比较无差别;L_(4-5)DRG内P2X3受体表达模型组明显高于假手术组,低、高剂量治疗组较模型组均明显降低,二甲亚砜组与模型组比较无明显区别。结论:1,8-桉叶素抑制CCI大鼠L_(4-5)DRG神经元P2X3受体过表达,从而缓解神经病理性疼痛症状。     

Proteomic analysis of rat brains in a model of neuropathic pain following exposure to electroconvulsive stimulation

Some reports have shown that electroconvulsive shock therapy is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. This study analyzes changes in protein expression in the brainstems of neuropathic pain model rats with or without electroconvulsive stimulation (ECS). A neuropathic pain model rat is produced by chronic constrictive injury (CCI) of the sciatic nerve. An ECS was administered to rodents once daily for 6 days after the CCI operation. After ECS, the latency to withdrawal from thermal stimulation was significantly increased. The expression of several proteins was changed after CCI. Ten proteins that increased after CCI then had decreased expression levels (close to control) after ECS, and 8 proteins that decreased after CCI then had increased expression levels (close to control) after ECS. In conclusion, ECS improved thermal hypersensitivity in a rat CCI model. Proteomic analysis showed that altered expression levels of proteins in the brainstem of CCI model rats returned to close to control levels after ECS, including many proteins associated with pain. This trend suggests an association of ECS with improved hypersensitivity, and these results may help elucidate the mechanism of this effect.     

Analgesic effect of intrathecally γ-aminobutyric acid transporter-1 inhibitor NO-711 administrating on neuropathic pain in rats

To investigate the analgesic effect of intrathecally administered γ-aminobutyric acid (GABA) transporter-1 inhibitor NO-711 on the sciatic nerve chronic constriction injury (CCI) rats. 5 days after intrathecal catheter placement, neuropathic pain model was established by CCI of sciatic nerve on rats. Withdrawal thresholds for mechanical allodynia and latency for thermal hyperalgesia were measured in all animals. All rats operated upon for CCI displayed decreased withdrawal thresholds for mechanical allodynia and latency for thermal hyperalgesia, which has significant difference compared with sham groups. After intrathecal NO-711 administration, withdrawal thresholds and latency were significantly increased on CCI rats compared with control group after 1 day. The results show that GABA transporter-1 inhibitor could effectively develop analgesic effect in sciatic nerve CCI rats’ model.     

Time-course of neuropathic pain in mice deficient in neuronal or inducible nitric oxide synthase

Nitric oxide which is synthesised by nitric oxide synthase (NOS) is involved in processes related to regeneration after nerve injury and neuropathic pain. Here we investigated functional aspects of the nociceptive system. For that purpose, the chronic constriction injury (CCI) model induced by loose ligation of the sciatic nerve was employed in C57Bl/6J wild-type (WT), nNOS and iNOS knock-out (−/−) mice. Their thermal and mechanical pain thresholds were then measured over a period of six weeks. In addition, ³H-DAMGO, ³H-CP 55.940, and ³H-l-glutamate binding, and neuronal (NeuN-immunostained) and astroglial (GFAP-immunostained) cell composition were studied. There were no significant differences in cell composition between the three strains used. Significant differences between CCI and sham-operated animals were found in nNOS−/− after day 6, in WT mice after day 10, and in iNOS−/− after day 17 post surgery. The mechanical pain threshold was normalised after day 45 post surgery in WT mice only. There were no changes in DAMGO and glutamate binding. However, we found significant differences in CP 55.940 binding in the spinal cord. It was concluded that NOS–cannabinoid interaction contributes to differences in nociceptive behaviour.     

大麻素CB_1受体活化对神经病理性疼痛大鼠脊髓背角嘌呤能P2X_2受体表达的抑制作用

目的:观察脊髓背角大麻素CB_1受体(CB_1R)在坐骨神经缩窄性损伤(CCI)所致的神经病理性疼痛中的作用及其对嘌呤能P2X_2受体表达的调节。方法:7~8周龄SD大鼠分为4组:(1)sham组;(2)CCI组;(3)CP55940+CCI组;(4)AM251+CP55940+CCI组。分别于CCI术前1 d,术后1、3、5、7、10、14 d测定热缩足反射潜伏期(TWL);免疫印迹技术检测各组大鼠损伤侧L_4~L_6段脊髓背角P2X_2受体表达。结果:CCI术后大鼠出现热痛敏,TWL明显缩短;鞘内给予非选择性大麻素受体激动剂CP55940可明显延长CCI大鼠TWL(P0.05);预先鞘内注射CB_1R拮抗剂AM251(0.05 mg/kg)可显著降低CP55940的镇痛效果(P0.05)。免疫印迹实验结果显示:CCI大鼠脊髓背角P2X_2受体在术后7、14 d表达明显增加(P0.05);鞘内给予CP55940可显著降低P2X_2受体表达(P0.05),而预先给予AM251可降低CP55940抑制P2X_2受体表达的效应(P0.05)。结论:脊髓背角CB_1受体激活对CCI所致的神经病理性疼痛具有良好的镇痛作用,其镇痛效应可能与抑制CCI大鼠嘌呤能P2X_2受体表达有关。     

神经病理性疼痛大鼠中脑导水管周围灰质腹外侧区NLRP3炎症小体激活水平研究

目的探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体在神经病理性疼痛大鼠中脑导水管周围灰质腹外侧区(vlPAG)的表达水平及其作用。方法选取SPF级SD大鼠20只,采用随机数字表法分为假手术组(Sham组)与慢性坐骨神经压迫性损伤组(CCI组),每组10只。于手术前后测定2组机械痛阈与热痛阈;Western blot检测2组NLRP3炎症小体各组分蛋白表达水平;RT-PCR检测2组NLRP3炎症小体各组分基因mRNA表达水平;酶联免疫吸附实验(ELISA)检测2组炎症因子白介素-lβ(IL^-1β)及白介素-18(IL^-18)表达水平;免疫荧光检测2组中NLRP3炎症小体在vlPAG的分布情况,并与小胶质细胞标志物IBA1进行共定位分析。结果与Sham组相比,CCI组术后3 d、7 d、14 d、21 d机械痛阈与热痛阈均明显降低(P<0.001);与Sham组相比,CCI组核心蛋白NLRP3、效应蛋白Caspase-1 p10及前体蛋白pro-Caspase-1表达水平均明显升高(P<0.001);与Sham组相比,CCI组NLRP3(P<0.001)、Caspase-1(P<0.001)及IL^-1β(P<0.01)mRNA表达水平均明显升高,炎症因子IL^-1β(P<0.001)与IL^-18(P<0.01)表达水平也明显升高;与Sham组相比,CCI组在vlPAG的NLRP3阳性细胞数增加,且与IBA1存在共表达。结论神经病理性疼痛大鼠vlPAG中NLRP3炎症小体被激活且表达水平增高,提示NLRP3炎症小体激活水平与神经病理性疼痛大鼠痛阈下降相关。     

加巴喷丁复合吗啡预防慢性压迫坐骨神经致痛觉敏化的疗效分析

目的观察加巴喷丁复合吗啡预防性镇痛对大鼠慢性压迫坐骨神经（CCI）后导致的机械缩足阈变化以及脊髓背角肿瘤坏死因子-α（TNF-α）表达的影响。方法随机选择重量（180±20）g的成年雄性SD大鼠24只,分为假手术组（S组）、模型组（M组）、预防性镇痛组（P组）和常规镇痛组（N组）。观察不同方式给药的模型组和对照组大鼠的行为学变化。术后10d分离脊髓通过免疫组化检测TNF-α水平的变化。结果术前各组大鼠机械痛阈差异无统计学意义,与M组相比,手术后各时段S、P、N组都存在不同程度的改变,差异均有统计学意义（P〈0.05）;P、N组TNF-α的积分光密度均值（IOD）水平分别为（0.2185±0.01980）、（0.2301±0.01386）,与M组的（0.2902±0.01325）比较明显降低,差异均有统计学意义（P〈0.05）。结论加巴喷丁复合吗啡对大鼠采用预防性镇痛有较好的效果,可显著降低CCI后导致的机械痛阈,降低TNF-α在脊髓背角的表达。