普瑞巴林对神经病理性痛大鼠行为学的影响

目的:探讨普瑞巴林对神经病理性痛大鼠行为学的影响.方法:建立大鼠神经病理性痛模型(CCI模型),取40只雄性Sprague-Dawley大鼠随机分成4组,Ⅰ组为空白对照组,Ⅱ组为假手术组,Ⅲ组为CCI+普瑞巴林治疗组,Ⅲ组在术后第1夭开始灌胃给予3 mg/kg普瑞巴林,Ⅳ组为CCI手术组.分别于术前0 d及术后1 d、3 d、5 d、7 d、9 d、11 d、14d以热辐射法测定热缩足反射潜伏期(Paw withdrawal thermal latency, PWTL),观察神经病理性痛大鼠行为学变化.结果:术后14 d,Ⅳ组和Ⅰ、Ⅱ、Ⅲ组相比较,大鼠后爪的热痛敏阈值明显降低(P<0.01);Ⅰ、Ⅱ、Ⅲ组之间相比,大鼠后爪的热痛敏阚值差异没有显著性(P>0.05).结论:普瑞巴林可以缓解神经病理性痛大鼠的慢性神经病理痛行为学表现.     

外源性的电磁干预对神经病理性疼痛大鼠的镇痛效果研究

目的:探讨外源性的电磁干预方法对神经病理性疼痛大鼠的镇痛效果。方法:将30只成熟的雄性SD大鼠随机等分成3组:空白对照组(Control),坐骨神经慢性压迫损伤(CCI)组以及坐骨神经慢性压迫损伤协同电磁刺激组(CCI+EMF)。CCI组和CCI+EMF组的20只大鼠建立坐骨神经慢性压迫损伤模型,CCI+EMF组大鼠行外源性的全身性电磁刺激干预(脉冲波形,频率15 Hz,强度30 Gs),每天刺激6小时。在CCI模型构建的第0、3、6、9、12及15天对大鼠测试和比较足底机械痛阈值、足底热痛阈值、运动功能评分和神经传导速率。结果:CCI组大鼠的足底机械痛阈值、足底热痛阈值及感觉神经传导速率从CCI手术后的第3天即出现显著性降低,其6、9、12、15天足底机械痛阈值、足底热痛阈值及感觉神经传导速率均显著低于Control组(P0.01),而运动功能评分均显著高于Control组(P0.05)。CCI+EMF组大鼠的足底机械痛阈值、足底热痛阈值及感觉神经传导速率在第9、12、15天显著高于CCI组大鼠(P0.05),而运动功能评分均显著高于CCI l组。结论:外源性的电磁刺激对于神经病理性疼痛大鼠具有良好的镇痛效果,有望成为一种临床治疗神经病理性疼痛的新的物理治疗手段。     

脊髓水平给予胍丁胺对鞘内吗啡镇痛的影响

目的：观察脊髓水平给予胍丁胺对鞘内吗啡镇痛作用的影响。方法：30只sD大鼠随机分为3组（n=10）：C1组：鞘内注射生理盐水（10出）;M1组：鞘内注射吗啡（15μg／10μl）;AMI组：鞘内同时给予吗啡15μg＋胍丁胺12．5μg／10出。所有大鼠均于鞘内给药后5min于跖部皮下注射蜜蜂毒50m（0．2mg）致痛,观察并纪录1h内大鼠的自发缩足反射次数。另30只SD大鼠分组为C2,M2和AM2（n=10）,每组给药分别同前,用来测定机械痛阈和热刺激阈值。结果：与C1组比较,M1组1h内大鼠的自发缩足反射次数显著减少,提示鞘内注射吗啡对蜜蜂毒诱致的自发痛具有显著性抑制作用（P〈0．05）;鞘内同时给予吗啡和胍丁胺（AM1组）,大鼠自发缩足反射次数进一步减少,与M1组比较具有显著性意义（P〈0．05）。与对照组C2组比较,M2组大鼠的热刺激闽值和机械性痛闽明显提高;AM2组热刺激潜伏期显著延长,机械刺激阈值显著提高;AM2组与M2组比较热刺激潜伏期和机械刺激阈值有统计学差异（P〈0．05）。结论：鞘内胍丁胺和吗啡联合用药可显著增强吗啡对蜜蜂毒诱致自发痛的抑制作用,具有加强效应。     

苦参碱对神经病理性大鼠背根神经节P2X3受体、疼痛行为学和疼痛阈值的影响

摘要 目的：探讨苦参碱对神经病理性大鼠背根神经节P2X3受体、疼痛行为学和疼痛阈值的影响。方法：选择Sprague-Dawley雄性大鼠30只,随机分为3组,包括模型组、试验组和假手术组。于大鼠造模成功1 d后,试验组给予30 mg/（kgod）的剂量在腹腔注射苦参碱溶液,1次/d;给予假手术组和模型组腹腔注射等量浓度为0.9 %的氯化钠溶液,1次/d,共14 d。进行自发疼痛行为学评分检测、机械痛阈值检测、热痛阈值检测、P2X2和P2X3mRNA相对表达量检测、P2X2和P2X3蛋白表达水平检测,以及氧化应激指标水平检测。结果：术后模型组与试验组自发性疼痛行为学评分与假手术组比均升高,自术后第5天起,与模型组比,试验组自发性疼痛行为学评分明显低于模型组（P<0.05）;自术后第3天起,相较于假手术组,模型组机械痛阈值、热痛阈值显著下降,相较于模型组,试验组自术后第5天起机械痛阈值、热痛阈值显著上升（均P<0.05）;术后第14天试验组与假手术组机械痛阈值、热痛阈值对比无差异（P>0.05）;模型组P2X2和P2X3mRNA、P2X2及P2X3蛋白比假手术组和试验组高（均P<0.05）,试验组和假手术组P2X2、P2X3mRNA、P2X2及P2X3蛋白比较无差异（P>0.05）;干预前及干预1、2周后模型组大鼠脊髓组织SOD比假手术组低,MDA比假手术组高;试验组大鼠脊髓组织SOD比模型组高,MDA比模型组低（均P<0.05）。结论：苦参碱可有效缓解神经病理性痛的所引发的机械痛觉和热痛觉,镇痛作用较好,机制可能在于其可使大鼠背根神经元中P2X2、P2X3受体下降相关,同时其在抑制神经病理性大鼠脊髓组织氧化应激反应方面有一定的作用,与其在对神经病理性痛大鼠脊髓组织神经元凋亡的抑制有密切关系。     

川芎嗪对慢性压迫性损伤大鼠神经病理痛行为学的影响

目的探讨川芎嗪对慢性压迫性损伤（CCI）大鼠行为学的影响。方法建立大鼠坐骨神经CCI神经病理痛模型,取40只雄性大鼠随机分成4组,Ⅰ组为空白对照组,Ⅱ组为假手术组,Ⅲ组为CCI＋川芎嗪治疗组,Ⅲ组在术后第1天开始腹腔注射100 mg/kg川芎嗪注射液,Ⅳ组为CCI手术组。分别于术前（0 d）及术后1、3、5、7、91、1、14 d以von Frey细丝法和热辐射法测定机械缩足反射阈值（mechanical withdrawal threshold,MWT）和热缩足反射潜伏期（thermal withdrawal latency,TWL）,观察CCI大鼠神经病理痛的行为学变化。结果术后14 d,Ⅳ组和I、Ⅱ、Ⅲ组相比较,大鼠后爪的机械和热痛敏阈值明显降低（P〈0.01）;I、Ⅱ、Ⅲ组之间相比,大鼠后爪的机械和热痛敏阈值差异没有显著性（P〉0.05）。结论川芎嗪可以缓解CCI大鼠的慢性神经病理痛行为学表现。     

鸡矢藤注射液和野木瓜注射液对大鼠足底皮下化学组织损伤诱致自发痛、痛敏和炎症的作用

研究市售中药制剂鸡矢藤注射液和野木瓜注射液有无抗伤害及抗炎作用。采用两种持续性痛动物实验模型——蜜蜂毒(bee venom,BV)模型和福尔马林(formalin,F)模型,评价鸡矢藤注射液和野木瓜注射液系统给药对持续性自发痛反应、原发性热和机械痛敏及炎症反应的作用效果。成年清醒大鼠足底皮下注射BV(0．2％,50μl)不仅可诱发注射侧长达1h以上的、持续的、单相性的自发痛反应(其表现为自发缩足反射行为)和之后出现的持续3—4d的原发性热和机械痛敏现象,而且注射爪出现明显的红、肿等炎症反应。皮下注射F(2．5％,50μl)则产生双相性自发痛反应。与盐水组比较,致痛前系统给予0．32、1．6和9．0ml／kg三个剂量的500％鸡矢藤注射液或250％野木瓜注射液,对BV或F诱致的1h自发缩足反射次数具有剂量依赖性抑制作用;致痛5min后分别给予鸡矢藤或野木瓜注射液对BV或F诱发的自发痛反应也产生显著的抑制作用。然而,致痛前或致痛后静脉注射鸡矢藤注射液或野木瓜注射液对BV诱致的原发性热／机械痛敏及炎症反应均无明显的抑制作用。纳洛酮(一种非选择性的阿片受体拮抗剂)不能翻转鸡矢藤或野木瓜注射液对BV产生的自发痛反应的镇痛作用,提示其镇痛作用不是由内源性阿片受体介导。本研究结果证实鸡矢藤或野木瓜注射液能预防和缓解临床持续性自发痛,但是对原发性热／机械痛敏及炎症反应均无抗伤害效应和抗炎作用。在中药镇痛抗炎有效成分的筛选和评价中,BV模型是一个理想的实验动物模型。     

改良CCI大鼠痛行为学检测与损伤区自发放电活动再观察

目的：应用改良CCI模型研究外周神经损伤后痛觉过敏和自发放电各自特征及相互关系。方法：雄性SD大鼠,随机分为CCI组和Sham组,分别于术前1天和术后1、4、7、9、11、14天测定机械刺激缩足反射阈值和热缩腿反射潜伏期,同时选取术侧机械刺激缩腿反射阈值低于4g或者术侧和健侧热缩腿反射潜伏期差异大于2s的CCI模型大鼠观察术后4-14天损伤区自发放电活动。结果：神经纤维损伤后,机械痛敏和热痛敏随时间表现为逐渐增强,同时在损伤区观察到三类放电模式：整数倍放电﹑阵发放电和周期放电。结论：术后大鼠机械痛阈和热痛阈逐渐降低,机械痛敏的产生和损伤区自发放电活动关系密切,不同的放电模式可能代表不同的传入信息。     

改良CCI 大鼠痛行为学检测与损伤区自发放电活动再观察

目的:应用改良CCI模型研究外周神经损伤后痛觉过敏和自发放电各自特征及相互关系.方法:雄性SD大鼠,随机分为CCI组和Sham组,分别于术前1天和术后1、4、7、9、11、14天测定机械刺激缩足反射阈值和热缩腿反射潜伏期,同时选取术侧机械刺激缩腿反射阈值低于4g或者术侧和健侧热缩腿反射潜伏期差异大于2s的CCI模型大鼠观察术后4-14天损伤区自发放电活动.结果:神经纤维损伤后,机械痛敏和热痛敏随时间表现为逐渐增强,同时在损伤区观察到三类放电模式:整数倍放电阵发放电和周期放电.结论:术后大鼠机械痛阈和热痛阈逐渐降低,机械痛敏的产生和损伤区自发放电活动关系密切,不同的放电模式可能代表不同的传入信息.     

鞘内联合给予米诺环素和IL-6的中和抗体对脊神经结扎模型所引起的热痛敏的镇痛作用

目的:研究鞘内联合给予米诺环素和IL-6的中和抗体在大鼠脊神经结扎(spinal nerve ligation,SNL)模型所引起的神经病理性痛中的镇痛作用。方法:建立大鼠SNL模型,分别在手术前和手术后鞘内给予米诺环素100μg、在手术后鞘内给予IL-6的中和抗体0.03μg、手术后鞘内联合给予两种药物,观察给药3天各组大鼠热刺激的缩足反应潜伏期(paw withdrawal latencies,PWL)。结果:①SNL手术前后给予米诺环素都可以提高大鼠的PWL(P<0.05),但SNL手术前给药对大鼠PWL的提升明显高于手术后给药(P<0.05)。②手术后给予IL-6的中和抗体可以有效提升SNL组的PWL(P<0.05),但是还是比给予生理盐水的假手术组大鼠的PWL明显减少(P<0.05)。③手术后联合给予两种药物可以明显逆转SNL组的PWL(P<0.05)。④联合给药对大鼠PWL的提高明显高于SNL手术后给予米诺环素组和给予IL-6的中和抗体组(P<0.05),但与手术前给予米诺环素组的PWL相比无明显差异(P>0.05)。结论:鞘内联合给予米诺环素和IL-6的中和抗体对SNL引起的神经病理性痛有明显的镇痛作用。     

鞘内联合给予米诺环素和IL-6的中和抗体对脊神经结扎模型所引起的热痛敏的镇痛作用

目的:研究鞘内联合给予米诺环素和IL-6的中和抗体在大鼠脊神经结扎(spinal nerve ligation,SNL)模型所引起的神经病理性痛中的镇痛作用.方法:建立大鼠SNL模型,分别在手术前和手术后鞘内给予米诺环素100 μg、在手术后鞘内给予IL-6的中和抗体0.03 μg、手术后鞘内联合给予两种药物,观察给药3天各组大鼠热刺激的缩足反应潜伏期(paw withdrawal latencies,PWL).结果:①SNL手术前后给予米诺环素都可以提高大鼠的PWL(P＜0.05),但SNL手术前给药对大鼠PWL的提升明显高于手术后给药(P＜0.05).②手术后给予IL-6的中和抗体可以有效提升SNL组的PWL(P＜0.05),但是还是比给予生理盐水的假手术组大鼠的PWL明显减少(P＜0.05).③手术后联合给予两种药物可以明显逆转SNL组的PWL(P＜0.05).④联合给药对大鼠PWL的提高明显高于SNL手术后给予米诺环素组和给予IL-6的中和抗体组(P＜0.05),但与手术前给予米诺环素组的PWL相比无明显差异(P＞0.05).结论:鞘内联合给予米诺环素和IL-6的中和抗体对SNL引起的神经病理性痛有明显的镇痛作用.     

Zonisamide: Antihyperalgesic efficacy,the role of serotonergic receptors on efficacy in a rat model for painful diabetic neuropathy

Aims

The purpose of this study was to compare the changes of antihyperalgesic effectiveness of zonisamide (25 and 50 mg/kg), an antiepileptic drug, on the early and late phases of neuropathy and to investigate the role of serotonergic descending inhibitory pain pathways in antihyperalgesic effectiveness of zonisamide in the streptozotocin-induced rat model for painful diabetic neuropathy.

Main methods

The hot-plate and tail-immersion, to determine thermal thresholds, and paw pressure withdrawal tests, to determine mechanical thresholds, were performed as hyperalgesia tests. To investigate the role of serotonergic pathway, 1 mg/kg ketanserin (5-HT_2A/2C antagonist) and ondansetron (serotonin 5-HT₃ receptor antagonist) were used.

Key findings

Zonisamide enhanced pain thresholds significantly in the 3rd, 6th and 8th weeks as the reference drugs morphine (5 mg/kg) and carbamazepine (32 mg/kg, tested only in the 3rd week). There were no observed differences on the potency of antihyperalgesic effect between weeks and between doses. Each antagonist reversed the effect of zonisamide in the hot-plate and tail-immersion tests significantly, but, relatively in the paw pressure withdrawal tests.

Significance

These results support the role for zonisamide in the management of diabetic neuropathic pain in all phases. Serotonin 5-HT_2A/2C and 5-HT₃ receptors are involved in the antihyperalgesic effect of zonisamide by enhancement of thermal threshold, and partially by mechanical threshold, so they may not mediate mechanical hyperalgesia in diabetic neuropathy.     

Nandrolone modulates the non-opioid and opioid analgesia and tolerance/dependence: role of sexual dimorphism

The aim of this investigation was to study the effect of the doping steroid nandrolone on metamizol and morphine-induced analgesia and tolerance/dependence in rats. Nandrolone per se did not change the basal nociceptive thresholds in both sexes. It diminished the analgesic effect of metamizol in females, revealed by tail flick test, and males, revealed by paw pressure and hot plate tests. In general, the action of nandrolone was to decrease the morphine-induced analgesia in female and male rats. This was strongly manifested by paw pressure and tail flick tests in male, and tail flick tests in female animals. Nandrolone slowed the development of opioid tolerance/dependence. It aggravated the withdrawal syndrome in the females and invigorated aggression in the males. The data provide evidence that anabolic steroid nandrolone might decrease the analgesic action of metamizol or morphine. The doping steroid could modulate opioid tolerance/dependence and the aggressive behavior in a gender dependent manner. The action of nandrolone is most likely due to profound long-term effects on the central nervous system and might be a gateway to addiction of other drugs of abuse.     

Proteomic analysis to identify early molecular targets of pregabalin in C6 glial cells

Pregabalin is a lipophilic amino acid derivative of γ‐amino butyric acid that displays anticonvulsant and analgesic activities against neuropathic pain. Although a role for glial cells as an important player in pain control and also as a new target for pain medicine has been suggested, the effect of pregabalin on glial cells has not been elucidated. In the present study, we have investigated the action of pregabalin on the glial cell proteome. To identify immediate early protein targets of pregabalin in glial cells, a differential proteomics approach in C6 rat glioma cells treated with pregabalin was used. Seven proteins that sensitively reacted to pregabalin treatment were identified using two‐dimensional gel electrophoresis and MALDI–TOF‐MS (matrix‐assisted laser‐desorption ionization–time‐of‐flight MS). The calcium‐ion‐binding chaperone, calreticulin, and the oxidative response protein, DJ‐1, were up‐regulated after pregabalin treatment. Hsp (heat‐shock protein)‐90‐β, cytoskeleton protein actin and myosin also showed quantitative expression profile differences. Functionally relevant to the proteome result, immediate actin depolymerization was observed after treatment with pregabalin. These results suggest a previously undefined role of pregabalin in the regulation of chaperone activity and cytoskeleton remodelling in glial cells.     

Systemic pregabalin attenuates facial hypersensitivity and noxious stimulus-evoked release of glutamate in medullary dorsal horn in a rodent model of trigeminal neuropathic pain

Pregabalin is effective in treating many neuropathic pain conditions. However, the mechanisms of its analgesic effects remain poorly understood. The aim of the present study was to determine whether pregabalin suppresses facial mechanical hypersensitivity and evoked glutamate release in the medullary dorsal horn (MDH) in a rodent model of trigeminal neuropathic pain. Nociceptive mechanical sensitivity was assessed pre-operatively, and then post-operatively 1 h following pregabalin or vehicle (saline) treatment on post-operative days 2 and 5 following infraorbital nerve transection (IONX). In addition, an in vivo microdialysis probe was inserted into the exposed medulla post-operatively and dialysate samples were collected. Glutamate release was then evoked by mustard oil (MO) application to the tooth pulp, and the effects of pregabalin or vehicle were examined on the MDH glutamate release. Glutamate concentrations in the dialysated samples were determined by HPLC, and data analyzed by ANOVA. IONX animals (but not control animals) showed facial mechanical hypersensitivity for several days post-operatively. In addition, tooth pulp stimulation with MO evoked a transient release of glutamate in the MDH of IONX animals. Compared to vehicle, administration of pregabalin significantly attenuated the facial mechanical hypersensitivity as well as the MO-evoked glutamate release in MDH. This study provides evidence in support of recent findings pointing to the usefulness of pregabalin in the treatment of orofacial neuropathic pain.     

Comparison of hyperalgesia induced by capsaicin injection and controlled heat injury: effect on temporal summation

The relationship between induction of central sensitization and facilitation of temporal summation to repetitive stimulation is still unclear. The aim of this study was to investigate temporal summation before and after the induction of secondary hyperalgesia by two different experimental methods: capsaicin injection and controlled heat injury. The effect of each injury model was assessed on a separate day with an interval of at least 5 days. Twelve healthy volunteers participated. Each experiment was performed using electrical, radiant heat, mechanical impact, and punctuate stimuli consecutively. The pain threshold (PT) to a single stimulus and the summation threshold to five repetitive stimuli for electrical (2?Hz) and radiant heat (0.83?Hz) were assessed within the secondary hyperalgesic area. The degree of temporal summation for stimulus intensities of 0.8, 1.0, and 1.2 times the baseline pain thresholds were evaluated by the increase in visual analogue scale (VAS) scores from the first to the fifth stimulus of the train. Further, the degrees of temporal summation were assessed for mechanical impact and punctuate stimuli within the primary and secondary hyperalgesic areas. The contra-lateral forearm served as control (no injury). The pain threshold and the summation threshold to electrical and heat stimuli decreased significantly within the secondary hyperalgesic area after the injury induced by both heat injury or capsaicin injection. However, there was no temporal summation for heat and electrical stimuli in either model. In contrast, for the mechanical impact and punctuate mechanical stimuli the degree of temporal summation was significantly facilitated in the secondary hyperalgesic areas compared with the baseline and the control arm in both models. In the primary hyperalgesic area, the degree of temporal summation was facilitated to mechanical impact and punctuate stimuli but only following the capsaicin injection. In conclusion, the temporal summation mechanism for mechanical stimuli was facilitated in the secondary hyperalgesic area.     

Comparison of hyperalgesia induced by capsaicin injection and controlled heat injury: effect on temporal summation

The relationship between induction of central sensitization and facilitation of temporal summation to repetitive stimulation is still unclear. The aim of this study was to investigate temporal summation before and after the induction of secondary hyperalgesia by two different experimental methods: capsaicin injection and controlled heat injury. The effect of each injury model was assessed on a separate day with an interval of at least 5 days. Twelve healthy volunteers participated. Each experiment was performed using electrical, radiant heat, mechanical impact, and punctuate stimuli consecutively. The pain threshold (PT) to a single stimulus and the summation threshold to five repetitive stimuli for electrical (2 Hz) and radiant heat (0.83 Hz) were assessed within the secondary hyperalgesic area. The degree of temporal summation for stimulus intensities of 0.8, 1.0, and 1.2 times the baseline pain thresholds were evaluated by the increase in visual analogue scale (VAS) scores from the first to the fifth stimulus of the train. Further, the degrees of temporal summation were assessed for mechanical impact and punctuate stimuli within the primary and secondary hyperalgesic areas. The contra-lateral forearm served as control (no injury). The pain threshold and the summation threshold to electrical and heat stimuli decreased significantly within the secondary hyperalgesic area after the injury induced by both heat injury or capsaicin injection. However, there was no temporal summation for heat and electrical stimuli in either model. In contrast, for the mechanical impact and punctuate mechanical stimuli the degree of temporal summation was significantly facilitated in the secondary hyperalgesic areas compared with the baseline and the control arm in both models. In the primary hyperalgesic area, the degree of temporal summation was facilitated to mechanical impact and punctuate stimuli but only following the capsaicin injection. In conclusion, the temporal summation mechanism for mechanical stimuli was facilitated in the secondary hyperalgesic area.     

脊髓p38丝裂原活化蛋白激酶激活参与坐骨神经压迫性损伤所致神经病理性痛

本研究旨在观察脊髓p38丝裂原活化蛋白激酶（p38 mitogen-activated protein kinase,p38 MAPK）在坐骨神经压迫性损伤所致神经病理性痛中的作用。雄性Sprague-Dawley大鼠鞘内置管后,4-0丝线松结扎左侧坐骨神经制作慢性压迫性损伤（chronic constriction injury,CCI）模型。CCI后第5天,鞘内注射不同剂量的p38 MAPK特异性抑制剂SB203580,并在给药前及给药后不同时间点,分别用von Frey机械痛敏监测仪和热辐射刺激仪监测大鼠损伤侧后爪机械和热刺激反应闽值,用免疫印迹技术（Western blot）观察给药前后脊髓磷酸化p38 MAPK（p-p38 MAPK）和磷酸化环磷酸腺苷反应元件结合蛋白（phosphorylated cAMP response element binding protein,pCREB）表达变化。结果发现：坐骨神经压迫性损伤引起脊髓p-p38 MAPK蛋白表达明显增加;鞘内注射SB203580能剂量依赖性逆转CCI引起的机械性痛觉异常和热痛觉过敏及脊髓水平p-p38 MAPK表达的增加,也明显抑制CCI引起的脊髓pCREB表达的增加。结果提示,脊髓水平p38 MAPK激活参与坐骨神经压迫性损伤所致神经病理性痛的发展,其作用可能通过pCREB介导。     

Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

Objective

To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain.

Methods

Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot.

Results

Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.).

Conclusion

ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.