共查询到20条相似文献,搜索用时 15 毫秒
1.
目的:探讨二甲双胍治疗坐骨神经慢性压迫损伤(chronic constriction injury,CCI)诱发大鼠神经病理性疼痛的效应。方法:SPF级健康雌性SD大鼠48只,7~9周龄,180~200 g,采用随机数字表法将其分为正常对照组(Naive组)、假手术组(Sham组)、CCI组和CCI+二甲双胍组(Met组),每组12只。二甲双胍采用灌胃方式给药,每次剂量45 mg/kg,从CCI建模前3 d开始给药,每天2次,持续至建模后第7天。分别于建模前(基线水平),术后3 d、7 d、10 d、14 d记录建模侧(左侧)后足机械缩足反射阈值(MWT)、热缩足潜伏期(TWL)和冷刺激诱发缩足次数(TNCW);第3、14天使用CatWalk步态分析系统测定各组大鼠的步态。结果:与Naive组比较,CCI组和Met组大鼠左足MWT降低、TWL缩短、TNCW减少(P0.05);CCI组大鼠左侧足印面积缩小、完整足印的平均强度减弱、站立时间缩短、步周长减小、摆动时间延长,并持续至建模后第14天(P0.05);Met组大鼠左侧足印面积缩小、完整足印的平均强度减弱;Sham组上述指标无明显改变。与CCI组相比,Met组大鼠左足MWT升高、TWL延长、TNCW增加(P0.05); Met组大鼠左侧足印面积增大、完整足印的平均强度增强、站立时间延长以及步周长增加(P0.05),摆动时间无明显改变。结论:二甲双胍可缓解CCI诱发神经病理性疼痛大鼠机械痛觉过敏和冷热痛觉过敏,且能改善神经病理性疼痛大鼠的步态。 相似文献
2.
The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain‐relief effects, and the influence of this treatment on the body and tissues. Male Sprague–Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2–8 days, while 2mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35mg/kg lidocaine, and the anti‐allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2–15mg/kg lidocaine. However, lesions were severe after administration of 35mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35mg/kg. Considering the ratio between useful effects and side effects, doses of 15mg/kg are suitable for intrathecal injection for relief of neuropathic pain. 相似文献
3.
To evaluate whether neuropathic pain affects autonomic nervous activities, we investigated daily change in cardiovascular parameters and plasma norepinephrine (NE) in free-moving rats after chronic constriction injury (CCI) on the sciatic nerve. Arterial blood pressure (BP), heart rate (HR), and the power spectrum of pulse interval variability were analyzed. Daily change in motor activity and nociceptive behavior was also measured from some CCI rats. In others, NE from daily blood samples was quantified and spontaneous pain was evaluated by daily monitoring of foot guarding behavior. We identified three stages in the daily change of cardiovascular parameters and plasma NE level over 3 weeks following CCI. The first stage (up to 3 days after the surgery) was characterized by increased MAP and HR, especially in the daytime, even though plasma NE was unchanged and motor activity decreased. The second stage (mid first to mid second postoperative weeks) was characterized by increased daytime MAP and HR, and the animals developed punctate hyperalgesia in the affected hindpaw. An NE surge that may have been related to spontaneous pain was present 3-5 days after CCI. The third stage, which appeared after the second postoperative week, was characterized by normalized MAP and decreased HR, and increased high-frequency (0.8-3.0Hz) power in pulse interval variability, which is an index of cardiac parasympathetic tone. These results demonstrated that cardiovascular function was kept high through sympathetic and non-sympathetic activity for 2 weeks after CCI, followed by a predominance of parasympathetic tone. 相似文献
4.
Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups ( P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model. 相似文献
5.
In addition to its regulatory effect on bone mass, calcitonin has been shown to relieve pain and alleviate peripheral circulatory disturbance in patients with Raynaud's syndrome and complex regional pain syndrome. In the present study, we investigated whether calcitonin ameliorates diminished blood flow and enhanced arterial contraction in response to noradrenaline in chronic constriction injury (CCI) of the sciatic nerve in rats. Following surgically induced CCI, laser Doppler flowmetry studies showed a significant decrease in plantar skin blood flow of the ipsilateral hind paw compared to the contralateral side. A subcutaneous bolus injection of elcatonin (20 U/kg), a synthetic derivative of eel calcitonin, significantly improved decreased skin blood flow in the ipsilateral side. In vitro analysis of plantar arteries isolated from the ipsilateral hind paw 7-13 days after the CCI procedure showed higher sensitivity to noradrenaline than the plantar arteries from the contralateral side. Elcatonin (0.1-10 nm) significantly reduced noradrenaline-induced contraction in the arteries of the ipsilateral side, whereas it had little effect on those of the contralateral side. These results suggest that calcitonin selectively ameliorates enhanced arterial contractility in CCI neuropathic rats, thus leading to its alleviating effect on peripheral circulatory disturbance. 相似文献
6.
目的:观察聚焦式低强度脉冲超声(focused low-intensity pulsed ultrasound,FLIPUS)对坐骨神经损伤模型(spared nerve injury,SNI)大鼠的镇痛作用,以及对脊髓神经重塑的影响.方法:建立SNI神经病理性疼痛大鼠模型.将30只雄性SD大鼠随机分成3组,假手术组、... 相似文献
9.
Ursolic acid (UA; 3b‐hydroxy‐12‐urs‐12‐en‐28‐oic acid), a natural pentacyclic triterpenoid carboxylic acid, has been known to possess potent anti‐inflammatory, antioxidant, and antinociceptive effects in various animal models. Therefore, this study was designed to investigate the antihyperalgesic, anti‐inflammatory, and antioxidant effects of UA at 5, 10, and 20 mg/kg of doses via per os ( p.o.) route for 14 days in chronic constriction injury (CCI)‐induced neuropathic pain in rats. Pain behavior in rats was evaluated before and after UA administration via mechanical and heat hyperalgesia. CCI caused significant increase in levels of pro‐inflammatory cytokines and oxido‐nitrosative stress. In addition, significant increase in myeloperoxidase, malondialdehyde, protein carbonyl, nitric oxide (NO), and total oxidant status (TOS) levels in sciatic nerve and spinal cord concomitant with mechanical and heat hyperalgesia is also noted for CCI‐induced neuropathic pain. Administration of UA significantly reduced the increased levels of pro‐inflammatory cytokines and TOS. Further, reduced glutathione is also restored by UA. UA also showed in vitro NO and superoxide radical scavenging activity. UA has a potential in attenuating neuropathic pain behavior in CCI model which may possibly be attributed to its anti‐inflammatory and antioxidant properties. 相似文献
10.
This study was designed to determine whether intrathecal octreotide (sandostatin), a synthetic octapeptide derivative of somatostatin, relieved thermal hyperalgesia and reduced the evoked spinal c-Fos expression in rats with chronic constriction injury (CCI) of the sciatic nerve. Intrathecal catheters were implanted in rats 7 days before CCI of the sciatic nerve over the left hind limb. After confirmation of the development of thermal hyperalgesia by decreased paw withdrawal latencies (PWL) to heat stimulation 7 days after CCI, intrathecal sandostatin at 20, 40, and 80 microg was administered, respectively. Rats in the control group received saline injections intrathecally. PWLs were evaluated at 30, 60, 120, 180, and 240 min after drug administration. Detection of Fos-like immunoreactivity (Fos-LI) neurons in the dorsal horn of the spinal cord following drug administration was performed after mechanical stimulation (stroking of the hind paws) on the 14th day after CCI. The reduction of PWL was attenuated significantly in the groups that received intrathecal sandostatin at 20, 40, and 80 g when compared with the saline group. However, PWL did not return to pre-CCI values in all groups. In the 40 microg group, PWL returned up to 76% of pre-CCI values 120 min after drug administration. Stroking of the hind paw in CCI-treated (ipsilateral) limbs induced a significantly greater expression of spinal Fos-LI neurons than that of non-CCI treated (contralateral) limbs in each group. The number of Fos-LI neurons in animals receiving intrathecal sandostatin was dose-dependently reduced. Expression of Fos-LI neurons in the 80 microg group was nearly completely inhibited. These data suggest that intrathecal sandostatin significantly relieved thermal hyperalgesia behaviorally but with limited effects and dose-dependently reduced spinal Fos-LI neurons expression evoked by stroking stimulation, which may reflect mechanical allodynia in rats with sciatic constriction injury. This implies that intrathecal sandostatin was effective in the treatment of neuropathic pain. 相似文献
11.
目的:观察大鼠坐骨神经慢性挤压伤模型所引起的行为学及病理形态学变化。方法:实验于2006-02/05在解放军军事医学科学院生物工程研究所完成。①SD大鼠24只,随机分为3组,坐骨神经结扎组12只制备右侧坐骨神经慢性挤压伤模型,正常对照组6只不干预,假手术组6只手术但不结扎,观察处理后42d内自发痛、触诱发痛、热刺激及冷刺激痛觉过敏等行为学变化。②SD大鼠54只,随机分为正常对照组、假手术组及坐骨神经结扎后3,7,14,21,28,35,42d组9组,处理同前,相应时间点处死大鼠观察坐骨神经和脊髓组织大体形态、苏木精-伊红染色和轴突髓鞘染色观察脊髓组织病理变化,电镜观察超微结构变化。结果:78只大鼠进入结果分析。①行为学变化:坐骨神经结扎组大鼠术后3d即出现明显的自发性疼痛,机械刺激痛阈值从术前的(17.33±5.42)g降至(3.28±1.37)g;热刺激爪退缩阈值从(12.13±2.37)s缩短至(10.43±1.65)s;冷刺激抬足次数从(3.50±1.09)次增加至(14.75±2.34)次。术后7 ̄14d这些阈值的变化逐渐达高峰,并持续至观察期结束(42d)。②坐骨神经结扎大鼠坐骨神经结扎部位及其远端轴突水肿,部分脱髓鞘。结论:大鼠坐骨神经慢性挤压伤模型可以产生明显的、稳定的自发性疼痛和诱发性疼痛等类似临床神经痛的症状和体征;其局部病理变化与症状相符。 相似文献
12.
目的探讨坐骨神经损伤与修复过程中相应脊髓前角外侧核运动神经元的形态学变化,并对神经元尼氏染色法的应用价值进行评估。方法采用硅胶管套接切断的大鼠坐骨神经模型,应用焦油紫染色、甲苯胺蓝染色和硫堇染色等3种尼氏法对伤后7、14、30d脊髓前角运动神经元进行形态学观察。结果应用3种染色方法均观察到坐骨神经伤侧脊髓前角外侧核大、中型运动神经元的形态结构和存活率与对照侧有明显差别。与对照侧比较,伤后7d伤侧脊髓神经元数目减少,存活率降低;伤后14d和伤后30d,尤其是伤后30d,伤侧脊髓神经元数目减少更显著,存活率下降更明显,有些神经元轮廓不清且尼氏体模糊。结论随着大鼠坐骨神经损伤时间的延长,其相应脊髓前角运动神经元的损伤程度逐渐增加,尤其是伤后30d退变非常明显。焦油紫染色方法是显示神经元尼氏体及反映神经元生活状态的简捷有效的方法。 相似文献
13.
目的:建立大鼠坐骨神经慢性压迫性损伤(CCI)动物模型,腹腔注射N-甲基-D-天冬氨酸(NMDA)受体竞争性拮抗剂2-氨基-5-磷酰基戊酸酯(AP5)后观察腹腔用药对大鼠坐骨神经慢性压迫性损伤(CCI)动物模型机械痛敏和热痛敏的影响.方法:48只成年Wistar大鼠,雌雄不拘,随机分成3组,即Ⅰ组,假手术组(Sham),8只大鼠;Ⅱ组,CCI组,8只大鼠;Ⅲ组,治疗组,32只大鼠再分为4个亚组,Ⅲa组(CCI+NS),mb组[CCI+AP50.1mg/(kg·d)]、Ⅷc组(CCI+AP50.2 mg/kg)、Ⅲd组(CCI+AP50.5 mg/kg),每个亚组8只大鼠.48只大鼠分别于术前(0 d)及术后1、3、5、7、14、21 d测量每组大鼠的机械性缩足反射阈值(MWT)和热缩腿潜伏期(TWL).结果:CCI组从术后第3天开始直到本实验观察的术后第21天,MWT和TWL均明显降低,与假手术组Sham相比具有显著性(P<0.01);CCI加生理盐水组大鼠与CCI组大鼠的MWT和TWL相比无明显改变(P>0.05);腹腔注射AP5各个剂量的CCI组在术后5~21 d的MWT和TWL明显增加,与给药前和生理盐水组相比具有显著性(P<0.01).结论:腹腔注射AP5有明显减轻大鼠CCI模型的机械性痛敏和热痛敏的作用. 相似文献
14.
目的:评估运动疗法对坐骨神经损伤小鼠运动功能恢复的促进作用。方法:将60只雄性C57BL/6小鼠随机分为假手术组、坐骨神经损伤组和运动治疗组,每组20只。通过挤压坐骨神经建立坐骨神经损伤小鼠模型。对各组小鼠脚趾形态和坐骨神经功能指数(Sciatic Functional Index,SFI)进行评估。通过免疫荧光染色观察各组小鼠神经纤维的形态及数量。使用透射电子显微镜检查小鼠坐骨神经损伤部位远端的有髓神经纤维数量。使用real-time PCR检测与神经损伤修复相关的基因。结果:与假手术组比较,坐骨神经损伤组小鼠脚趾不能张开,SFI高且下降速度慢,差异有统计学意义(P<0.001)。与坐骨神经损伤组比较,运动治疗组小鼠脚趾张开功能轻度恢复,SFI下降速度快,差异有统计学意义(P<0.001)。免疫荧光染色结果显示:坐骨神经损伤组受损部位远端神经纤维数量少,密度低;而运动治疗组受损部位远端神经纤维数量和密度均升高。电镜结果显示:与假手术组比较,坐骨神经损伤组小鼠受损部位远端有髓神经纤维比例降低,差异有统计学意义(P<0.001);与坐骨神经损伤组比较,运动治疗组小鼠受损部位远端有髓神经纤维比例升高,差异有统计学意义(P<0.01)。Real-time PCR结果显示:与假手术组比较,坐骨神经损伤组BDNF,Mpz和Cdh1基因表达均降低(P<0.01或P<0.001),Artn基因表达升高(P<0.001);与坐骨神经损伤组比较,运动治疗组BDNF,Mpz,Cdh1,Gap-43,cJun基因表达水平升高(P<0.01或P<0.001),Artn基因表达降低(P<0.01)。结论:运动疗法对坐骨神经损伤小鼠的运动功能恢复有促进作用。 相似文献
15.
Introduction: The sciatic nerve is one of the peripheral nerves that is most prone to injuries. After injury, the connection between the nervous system and the distal organs is disrupted, and delayed treatment results in distal organ atrophy and total disability. Regardless of great advances in the fields of neurosurgery, biological sciences, and regenerative medicine, total functional recovery is yet to be achieved. Areas covered: Cell-based therapy for the treatment of peripheral nerve injuries (PNIs) has brought a new perspective to the field of regenerative medicine. Having the ability to differentiate into neural and glial cells, stem cells enhance neural regeneration after PNIs. Augmenting axonal regeneration, remyelination, and muscle mass preservation are the main mechanisms underlying stem cells’ beneficial effects on neural regeneration. Expert opinion: Despite the usefulness of employing stem cells for the treatment of PNIs in pre-clinical settings, further assessments are still needed in order to translate this approach into clinical settings. Mesenchymal stem cells, especially adipose-derived stem cells, with the ability of autologous transplantation, as well as easy harvesting procedures, are speculated to be the most promising source to be used in the treatment of PNIs. 相似文献
16.
目的探讨坐骨神经损伤与再生修复过程中相应脊髓前角运动神经元的形态学变化和嗅被膜细胞(OECs)对神经元的保护作用。方法采用硅胶管套接切断的大鼠坐骨神经实验模型,将30只大鼠随机分为两组,治疗组硅胶管内注射OECs悬液,对照组注射生理盐水(SAL),应用尼氏法对术后7d、14d、30dSAL组与OECs组脊髓前角运动神经元进行形态学观察,比较两组同类神经元的存活率。结果OECs组治疗侧脊髓前角外侧核大、中型运动神经元的形态结构和存活率与对照组有明显差别。术后7d,OECs组治疗侧神经元数目较SAL组伤侧丢失减少,存活率上升。术后14d和30d,OECs组治疗侧神经元数目较SAL组伤侧明显增加,存活率明显升高,大多数神经元轮廓清楚,尼氏体清晰。结论OECs能减少坐骨神经损伤后相应脊髓前角运动神经元的退行性变。 相似文献
17.
目的探讨BALB/c小鼠坐骨神经损伤后应用苦参碱后对坐骨神经相应脊髓节段中gap-43的表达变化。方法健康成年BALB/c小鼠320只,单侧坐骨神经切断吻合后,随机分组给药,不同时间获取L4-6脊髓节段,用Real time-PCR检测坐骨神经相应脊髓节段gap-43的表达变化,同时进行髓鞘LFB染色观察坐骨神经的恢复情况。结果 Real time-PCR结果显示高剂量和中剂量组12h,24h3d5d1w,2w,4w,gap-43表达量明显高于低剂量组和空白对照组,8w各组比较无明显差异。LFB染色表明高中剂量组坐骨神经恢复情况明显优于低剂量组和对照组。结论坐骨神经损伤后应用苦参碱对坐骨神经脊髓相应节段细胞中gap-43的活化起到促进作用,减少炎症细胞的浸润从而达到促进神经再生的目的。 相似文献
18.
The expression of c-Fos protein has been used as a relative marker of nociceptive neuronal activity in the spinal cord following various noxious stimuli. Experiments were conducted to examine c-Fos expression in lumbar spinal cord (L3-L6) following chronic constriction injury (CCI) in relation to nociceptive behavior over longer survival period up to 28 days. Development of mechanical allodynia was observed in the ipsilateral hind paw of CCI rats at day 3 and lasted up to 28 days. In contrast, the spinal c-Fos expression in CCI rats appeared in a biphasic manner. The highest number of c-Fos positive neurons occurred during the first week, followed by a decline at 7 and 14 days and reappearance at day 28 following injury. The early increase of c-Fos expression correlated with allodynia development, however, at longer survival period (28 days) c-Fos positivity become comparable in both CCI and sham groups despite their obvious behavior differences. Our results suggest that, at least in the CCI model, the c-Fos protein expression should not be considered as a reliable index of pain sensation disorders. 相似文献
19.
Effects of chronic constriction injury (CCI) and sham surgery of both sciatic nerves were evaluated for reflex lick/guard (L/G) and operant escape responses to thermal stimulation of rats. Experiment 1 compared L/G and escape responses to 0.3 degrees C, 43 degrees C, and 47 degrees C stimulation during a period of 60 days after CCI. Experiment 2 evaluated escape from 44 degrees C, 47 degrees C, and 10 degrees C for 100 days after CCI. The rats escaped from heat or cold stimulation of the paws in a dark compartment by climbing on a thermally neutral platform in a brightly lit compartment. For reflex testing, a single compartment provided no escape option. There was no significant effect of bilateral CCI on reflex or escape responses to nociceptive heat. However, there were long-term increases in the duration of L/G responding during trials of 0.3 degrees C stimulation and in the duration of escape responding to 10 degrees C. Hyperalgesia for cold was confirmed by a preference test, with a 2-compartment shuttle box with one floor heated (45 degrees C) and the other floor cooled (10 degrees C). Occupancy of the heated compartment was significantly increased by CCI (indicating a relative aversion for cold). PERSPECTIVE: For preclinical testing of treatments for allodynia/hyperalgesia after nerve injury, it is crucial to use methods of testing that are sensitive to effects on nociception throughout the neuraxis. Operant escape testing satisfies this criterion and is sensitive to bilateral CCI of rats, which avoids asymmetric postural/motor influences of unilateral CCI. 相似文献
20.
目的:观察电针对坐骨神经损伤大鼠行为学、神经生长因子-3及其受体Trk C的影响,探讨电针治疗坐骨神经损伤的生物学机制。方法:建立大鼠坐骨神经夹持损伤模型,观察各组大鼠的行为学改变与背根神经节(DRG)中NT-3与Trk C表达情况。结果:模型组、模型对照组的大鼠行为学检测表明,造模后大鼠的感觉功能显著下降(P<0.05),电针治疗后有显著改善(P<0.05),与正常组无显著差异;电针组的NT-3与Trk C表达显著升高(P<0.05),第20天时模型组与正常组相比,NT-3分泌显著增多(P<0.05)。结论:电针治疗可以通过提高NT-3与Trk C的表达,维持神经元存活,促进受损神经修复,改善坐骨神经损伤大鼠的感觉功能。 相似文献
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