Cav3.2通道对背根节慢性压迫痛大鼠脊髓CaMKⅡ表达的影响

目的:观察Cav3.2通道对背根节慢性压迫痛大鼠脊髓CaMKⅡ表达的影响,探讨Cav3.2-CaMKⅡ通路在神经病理性疼痛中的作用。方法:雄性SD大鼠60只,体重250±20 g,随机分为5组,每组12只(其中行为学实验8只,免疫印迹实验4只)。分别是正常对照组(C组);模型组(CCD组);生理盐水组(NS组);错义寡聚核苷酸组(MS-Cav3.2组);反义寡聚核苷酸组(AS-Cav3.2组)。分别于鞘内置管前(T1),鞘内置管后3 d(T2),鞘内给药后1 d(T3)、4 d(T4),CCD模型制备后5d(T5)、10 d(T6)、15 d(T7)检测大鼠机械缩腿阈值(mechanical withdrawal threshold,MWT)和热缩足潜伏期(thermal withdrawal latency,TWL)。并于CCD模型制备后5 d,各组取4只大鼠处死,取脊髓腰膨大,采用免疫印迹法检测Cav3.2及CaMKⅡ的表达。结果:与C组比较,CCD组大鼠在模型制备后第5 d、10 d、15 d时MWT及TWL均显著降低。鞘内注射NS和Cav3.2错义寡聚核苷酸对CCD大鼠MWT及TWL无影响,鞘内注射Cav3.2反义寡聚核苷酸可增加CCD大鼠MWT和TWL,减轻大鼠机械痛敏和热痛敏。C组大鼠脊髓Cav3.2和CaMKⅡ蛋白均有表达。大鼠在制备CCD模型后5 d Cav3.2及CaMKⅡ蛋白表达均显著增加。鞘内注射NS及Cav3.2错义寡聚核苷酸对Cav3.2及CaMKⅡ蛋白表达无影响,鞘内注射Cav3.2反义寡聚核苷酸则可显著抑制Cav3.2及CaMKⅡ蛋白的表达。结论:抑制脊髓Cav3.2通道的表达可降低慢性背根节压迫痛大鼠脊髓CaMKⅡ的表达。     

脊髓背根入髓区切开治疗癌性神经病理性疼痛的远期疗效

目的:探讨脊髓背根入髓区(dorsal root entry zone,DREZ)切开术治疗癌性神经病理性疼痛的远期疗效及安全性。方法:收集癌性神经病理性疼痛病人4例,其中3例为直肠癌侵犯骶神经致会阴区神经病理性疼痛,1例为左侧乳腺癌侵犯臂丛神经导致上肢神经病理性疼痛。4例均接受患侧损伤和疼痛节段脊髓背根入髓区切开术治疗,显微镜下用双极电凝切开病变节段脊髓背根的入髓区。随访2年以上,分别于术后2周、术后每半年采用视觉模拟评分(visual analogue scale,VAS)评估手术疗效。结果:术后2周,2例疼痛消失,2例疼痛缓解>75%。随访2年,疗效满意率逐渐下降,2例疼痛缓解>75%,1例疼痛缓解60%,1例术后6月死亡。并发症发生情况:同侧下肢深感觉障碍3例,痛觉过敏2例,在术后6月随访时均有不同程度恢复。结论:脊髓背根入髓区切开术是一种治疗癌性神经病理性疼痛的安全、有效的措施。     

脊髓损伤后疼痛的神经病理性机制

脊髓损伤（spinal cord injury，SCI）后疼痛的表现多种多样，疼痛的时间可能是持续性的、间歇性的或阵发性的，疼痛可以不同的性质出现，在同一部位或不同区域常可以体验到一种以上性质的疼痛或以痛觉过敏的形式出现，疼痛的强度或高或低，各种内外在刺激（如触物、冷热刺激、激动等）常可诱发疼痛。疼痛与精神源性因素无关，但心理和精神的失调可能同时出现，究其原因目前尚不十分清楚。因此，SCI后疼痛的分类方法也不尽相同。     

大鼠坐骨神经慢性压迫后脊髓背角GCH1基因表达与疼痛的关系

目的:探讨大鼠坐骨神经慢性压迫(chronic constriction injury,CCI)后,脊髓背角内三磷酸鸟苷环化水解酶1 (GTP cyclohydrolase 1,GCH1)基因的表达变化与神经病理性疼痛产生的关系.方法:wistar大鼠64只被随机分为CCI组和Sham组,每组32只.对CCI组大鼠行右侧坐骨神经结扎;建立CCI模型,Sham组仅暴露坐骨神经不结扎,于术前1天及术后1、3、7、10、14、21、28天测定大鼠机械痛阈值,并分别在术后3、7、14、28天职腰4～6段脊髓,进行免疫组化和Western Blotting检测,观察脊髓背角GCH1表达的变化情况.结果:CCI组大鼠术后各时间点后肢机械痛阈值均显著低于Sham组(P＜0.05),术后第1天开始疼痛阈值便明显降低,直至术后第28天,均低于术前水平(P＜0.05).免疫组化结果显示:CCI组大鼠术后脊髓背角神经元GCH1的表达呈先升高后降低的趋势;与Sham组相比,术后各时间点GCH1的表达均明显增高(P＜0.05).Western Blotting检测与免疫组化结果基本一致,CCI组术后3天、7天、14天GCH1表达均高于Sham组(P＜0.05).结论:周围神经损伤引起的痛觉过敏随脊髓背角内GCH1表达升高而增强,随其表达降低而减轻,可以认为GCH1可能参与了神经病理性疼痛的形成.     

脊髓损伤患者神经病理性疼痛现况调查及相关影响因素分析

目的 调查脊髓损伤患者神经病理性疼痛（NP）现况,并分析其相关影响因素。 方法 先用DN4量表在所有诊断为脊髓损伤的患者中筛选出伴有NP的患者,搜集70例脊髓损伤伴NP患者的性别、年龄、文化程度、职业、平均月收入、损伤部位、婚姻状态等一般调查资料,然后再对筛选出来的患者用简化的McGill疼痛问卷表（SF-MPQ）进行NP现况调查,记录患者的疼痛目测类比法（VAS）评分以及疼痛评级指数(PRI),包括PRI-感觉项、PRI-情感项及PEI等平均得分;采用SPSS13.0统计软件对患者的基本资料进行单因素和多因素统计分析,分析患者NP的影响因素。 结果 ①患者的平均疼痛目测类比法（VAS）评分4.37分;SF-MPQ调查的平均PRI得分8.23分,PRI-感觉项平均得分5.2 3分,PRI-情感项平均得分3.00分;现在疼痛强度(PPI)平均程度为1.86,PPI介于轻痛和难受之间,PPI中出现最多的是难受这个描述词。疼痛描述词按出现频率排在前三位的是刺痛、烧灼痛和坠胀痛。有60例（85.7%）患者认为疼痛对其情感状态造成影响,出现最多的是疲惫耗竭感这个描述词。②单因素分析显示损伤程度、文化程度、婚姻状况、家庭人均月收入、家人支持与否以及是否用药是NP的影响因素（P<0.01）,而性别、年龄、病程、损伤部位、职业等因素与VAS评分无明显相关性（P>0.05）;多因素Logistic回归分析显示,未婚、损伤程度重为NP的独立保护因素（OR＜1）,家庭人均月收入低、没有家人支持、没有用药为NP的独立危险因素（OR＞1）。 结论 脊髓损伤患者NP感觉多样,疼痛程度中等,绝大多数患者情感状态受到影响;未婚和损伤程度重为独立保护因素,家庭人均月收入低、没有家人支持及没有用药为其独立危险因素。     

大鼠脊髓背角TRPV4在背根神经节持续受压致神经病理性疼痛中的作用

目的:探讨大鼠背根神经节(dorsal root ganglion,DRG)持续受压(chronic compression of right side dorsal root ganglion,CCD)后脊髓背角瞬时感受器电位离子通道4(TRPV4)基因及蛋白变化,明确脊髓背角TRPV4在CCD致神经病理性疼痛中的作用。方法:采用健康成年雄性Wistar大鼠,共36只,随机分为3组,分别为空白对照组、CCD手术组、CCD+钌红组。制备大鼠背根神经节持续受压模型,于术前1天、术后第7天、给药前及给药2h后,测量大鼠机械刺激缩爪反应阈值,观察机械痛阈的变化;利用RT-PCR及Western Blot技术检测各组大鼠手术侧脊髓背角TRPV4基因及蛋白表达的变化。结果:与空白对照组相比,术后第7天,CCD组大鼠术侧机械痛阈值明显下降(P0.001),同侧脊髓背角TRPV4基因及蛋白表达升高(P0.05);与给药前相比,给予钌红2h后,术侧机械痛阈值明显升高(P0.001),同侧脊髓背角TRPV4基因及蛋白表达下降(P0.05)。结论:CCD后大鼠术侧机械痛阈下降,脊髓背角TRPV4基因及蛋白表达升高;钌红可部分逆转CCD后痛觉过敏,部分降低脊髓背角TRPV4基因及蛋白表达。脊髓背角TRPV4参与CCD后大鼠神经病理性疼痛形成。     

杏仁核损毁对神经病理性疼痛大鼠疼痛症状及脊髓小胶质细胞活化的影响

目的:探讨损毁基底外侧杏仁核(Basolateral amygdala,BLA)对神经病理性疼痛大鼠疼痛症状及脊髓小胶质细胞活化的影响。方法:选择60只200~250 g纯种雄性SD大鼠,采用坐骨神经慢性缩窄手术(Chronic constriction injury,CCI)制备神经病理性疼痛模型,随机分为3组(n=20):模型组(Model),模型+BLA损毁组(Model+BLA lesions)和模型+假手术组(Model+sham),模型+BLA损毁组于CCI术后7天采用立体定位辅助下将损毁电极插入BLA行阳级损毁。同时选取20只同周龄大鼠作空白对照组(Blank),模型+假手术组则仅行立体定位并插入未通电的损毁电极。观察各组CCI术前2 d、术后1、4、7、11、14、17及21 d固定时间点的自发性痛行为,采用von Frey纤维和热辐射法分别测量以上时间点的机械性缩足反射阈值(Withdrawal mechanical threshold,MWT)和热刺激爪退缩阈值(Thermal withdrawal latency,TWL);采用荧光免疫组化法检测术后21天脊髓大麻素受体2(Cannabinoid receptor 2,CB2)及特异表达补体C3受体(Complement receptor 3,OX-42)的荧光积分光密度(Integral optical density,IOD)来评价脊髓小胶质细胞的活化情况;酶联免疫吸附法检测脊髓血浆肿瘤坏死因子(Tumor necrosis factor-α,TNF-α)和白介素-1β(interleukin-1β,IL-1β)水平来评价炎症反应情况。结果:与空白组相比,模型组的MWT和TWL水平降低,脊髓小胶质细胞CB2和OX-42的IOD增强及脊髓TNF-α和IL-1β水平升高;BLA损毁后可改善以上异常,模型+BLA损毁组的MWT和TWL水平升高,脊髓小胶质细胞CB2和OX-42的IOD的增强及脊髓TNF-α和IL-1β水平的升高均被抑制,均优于模型组和模型+假手术组(P<0.05),但与空白组的差异仍有统计学意义(P<0.05)。结论:损毁BLA可改善神经病理性疼痛大鼠的疼痛症状,同时对脊髓小胶质细胞活化有抑制作用并降低炎症反应。     

脊髓电刺激治疗神经病理性疼痛的应用进展

脊髓电刺激(SCS)通过电脉冲信号阻断疼痛信号传递,干扰疼痛传导通路,激活阿片通道,刺激蓝斑系统及调节γ-氨基丁酸能系统,从而发挥抑制或减轻疼痛的作用。目前被应用于带状疱疹后神经痛、腰椎术后疼痛综合征、幻肢痛、痛性糖尿病神经病变、头面部神经痛、阴部神经痛等神经病理性疼痛的治疗中。     

脊髓电刺激对神经病理性疼痛镇痛作用及相关机制研究

目的:探索脊髓电刺激(spinal cord stimulation, SCS)对小鼠神经病理性疼痛的镇痛作用并阐明相关机制。方法:30只健康成年雄性野生型CD1小鼠随机分为对照组(Sham)、坐骨神经结扎损伤组(chronic constriction injury, CCI)和治疗组(CCI+SCS),每组10只。通过行为学观察SCS对外周神经损伤引起的机械痛敏和热痛敏的缓解情况,以及对小鼠运动功能影响程度;采用电生理方法记录各组小鼠背根神经节(dorsal root ganglion, DRG)中小神经元的兴奋性;通过酶联免疫吸附试验测定DRG内炎性因子TNF-α的表达水平。结果:与对照组比较,CCI组小鼠机械痛阈值和热痛阈值明显降低(P <0.05)。治疗组与CCI造模组比较,SCS可提高小鼠的机械痛和热痛阈值。同时,各组转棒实验评分无差异。电生理及酶联免疫吸附试验结果提示外周神经损伤后,同侧小鼠背根神经节(dorsal root ganglion, DRG)神经元的兴奋性增强,同时DRG内TNF-α的释放增加,治疗组与CCI组比较,SCS可以明显抑制DRG神经元的兴奋性增强(P <0.05)和DRG内TNF-α的释放增加(P <0.05)。结论:SCS通过抑制外周神经损伤导致的DRG神经元的兴奋性增强,从而有效地减缓小鼠CCI导致的机械感觉过敏和热痛敏,并可减少CCI小鼠DRG中TNF-α的表达水平。     

血神经屏障和Claudin-1蛋白在大鼠慢性神经病理性疼痛中的作用

目的:观察慢性神经病理性疼痛大鼠坐骨神经的血神经屏障(BNB)变化,并探讨紧密连接蛋白Claudin-1在其中的作用.方法:健康雌性SD大鼠分为3组:对照组(Control组)、假手术组(Sham组)和慢性坐骨神经压迫损伤组(CCI组).对照组不做处理;Sham组仅分离暴露大鼠右侧坐骨神经,不结扎;CCI组暴露大鼠右侧...     

Spinal Cord Stimulator Relieves Neuropathic Pain in a Patient With Radiation-Induced Transverse Myelitis

▪ Abstract:   We present a patient with intractable neuropathic pain because of radiation-induced transverse myelitis unresponsive to medical treatment. After a successful trial of spinal cord stimulation, a permanent stimulator was implanted. Improvement was noted in verbal pain score, medication usage and function. Spinal cord stimulation may offer a therapeutic option for patients with neuropathic pain resulting from transverse myelitis and should be considered when other treatments fail. ▪     

鞘内注射FSTL1重组蛋白对大鼠脊髓损伤后中枢性疼痛的影响

【目的】了解鞘内注射FSTL1重组蛋白对脊髓损伤后中枢性疼痛模型大鼠痛行为学影响。【方法】成年Wistar 雌性大鼠32只,随机分为4组,每组8只,分别为：空白对照组、假手术组、模型组和鞘内注射FSTL1＋模型组（FSTL组）。分别于造模前和模型建立后的4 h、12 h、24 h、d2、d4、d6、d10、d14、d21测定各组大鼠机械痛敏（机械缩腿阈值,mechanical withdrawal threshold ,MWT）和热痛敏（热缩腿潜伏期,thermal withdrawal latency ,TWL）。【结果】大鼠MWT及TWL测定结果表明：四组大鼠实验前MWT、TWL基础值相比较无统计学差异（ P ＞0．05）。假手术组监测各时间点的MWT、TWL与实验前基础值及空白对照组比较皆无统计学差异（ P ＞0．05）;模型组与术前基础值和假手术组相比较,大鼠同侧后足的MWT 在术后4 h、12 h、24 h、d2、d4、d6、d10、d14、d21时间点均明显降低（ P ＜0．05）,在术后d14降低到峰值,术后d21仍低于正常水平,大鼠同侧后足的TWL值在术后4 h、12 h、24 h、d2、d4、d6、d10、d14、d21时间点均明显缩短,术后d14缩短到最低值,术后d21仍低（ P ＜0．05）;鞘内FSTL组与模型组相比较,MWT术后4 h、12 h、24 h、d2、d4、d6、d10、d14、d21均明显增加（ P ＜0．05）,TWL值明显延长（ P ＜0．05）;鞘内 FSTL组与假手术组相比较,术后4 h、12 h、24 h、d2时间点的MWT 及 TWL值无明显差异（ P ＞0．05）。术后d4、d6、d10、d14、d21时间点MWT值明显低于假手术组,TWL值较假手术组明显缩短（ P ＜0．05）。【结论】鞘内注射FSTL1重组蛋白能明显减轻脊髓损伤后中枢性疼痛模型大鼠机械痛敏和热痛敏,提示FSTL1与中枢性疼痛信息的传递关系密切相关,并在中枢性疼痛的痛觉超敏（ hyper‐algesia）的产生和维持中具有重要作用。     

地塞米松对罗哌卡因大鼠脊髓神经毒性的影响

[目的]观察地塞米松（Dex）对1％罗哌卡因（Rop）引起的大鼠脊髓神经细胞毒性的影响。[方法]鞘内置管成功且无运动障碍以及伤口感染雄性SD大鼠72只随机分为3组（ n ＝24）,每组大鼠随机分为4个亚组,每个亚组6只大鼠。N组（对照组）经导管注入0．9％氯化钠40μL。R组（Rop组）注入1％ Rop 40μL。DR组（Rop＋Dex组）注入1％ Rop 40μL＋ Dex粉剂100μg。各组中任一亚组大鼠在置管前即刻（T0）,第1次注药前即刻（T1）,注药后6 h（T2）,12 h（T3）,4个时相均从股动脉采血约0．5 mL ,检测血清髓磷脂碱性蛋白（MBP）含量;采血后,经灌注取腰膨大处脊髓,电镜下观察其超微结构改变并行细胞凋亡检测。[结果]在T2、T3时相的MBP含量, R组以及DR组明显高于N组（ P＜0．05）,R组与DR组比较MBP亦显著增高（ P＜0．05）,与T0比较,R组以及DR组在T2和T3时相MBP明显升高（ P ＜0．05）,而N组则较为稳定;R组电镜下可见大多数神经元固缩,粗面内质网扩张,线粒体结构模糊,有少数神经元完全变性,有髓神经纤维广泛严重脱髓鞘;而DR组大多数神经元结构清楚,神经组织有局灶的轻度水肿,N组无明显改变。R组鞘内给药后T2、T3时相可见大量凋亡细胞分布,以神经胶质细胞为主;与N组及T0时相比较,其凋亡指数（AI）显著性增高（ P＜0．05）;DR组亦出现凋亡细胞,较N组增多（ P ＜0．05）;但较R组明显减少（ P ＜0．05）。[结论]Dex对Rop的神经毒性有明显的抑制作用。     

Management of Postherniorrhaphy Chronic Neuropathic Groin Pain: A Role for Dorsal Root Ganglion Stimulation

Chronic neuropathic groin pain is a sequela of hernia surgery that occurs at unacceptably high rates, causing widespread impacts on quality of life. Although the medical community is beginning to recognize the role of surgical technique in the initiation and maintenance of postherniorrhaphy neuropathic pain, little information exists regarding pain management strategies for this condition. This review presents a summary of the pain condition state, its treatment options, and treatment recommendations. Both literature review and clinical experience were used to develop a proposed a treatment algorithm for the treatment of postherniorrhaphy pain. The development of chronic pain may be prevented via a number of perioperative measures. For pain that is already established, some surgical approaches including inguinal neurectomy can be effective, in addition to standard pharmacological treatments and local infiltrations. An unmet need may still exist with these options, however, leaving a role for neuromodulation for the treatment of intractable cases. A pain management algorithm for iterative interventions including stimulation of the dorsal root ganglion (DRG) is described. It is expected that cross‐disciplinary awareness of surgeons for nonsurgical pain management options in the treatment of chronic neuropathic postherniorrhaphy pain will contribute to better clinical outcomes.     

Gabapentinoids Are Effective in Decreasing Neuropathic Pain and Other Secondary Outcomes After Spinal Cord Injury: A Meta-Analysis

Objective

To examine the effectiveness of gabapentin and pregabalin in diminishing neuropathic pain and other secondary conditions in individuals with spinal cord injury (SCI).

Data Sources

A systematic search was conducted using multiple databases for relevant articles published from 1980 to June 2013.

Study Selection

Controlled and uncontrolled trials involving gabapentin and pregabalin for treatment of neuropathic pain, with ≥3 subjects and ≥50% of study population with SCI, were included.

Data Extraction

Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen's d to calculate standardized mean difference (SMD), SE, and 95% confidence interval (CI) for primary (pain) and secondary outcomes (anxiety, depression, sleep interference) was conducted.

Data Synthesis

Eight studies met inclusion criteria. There was a significant reduction in the intensity of neuropathic pain at <3 months (SMD=.96±.11; 95% CI, .74–1.19; P<.001) and between 3 and 6 months (SMD=2.80±.18; 95% CI, 2.44–3.16; P<.001). A subanalysis found a significant decrease in pain with gabapentin (SMD=1.20±.16; 95% CI, .88–1.52; P<.001) and with pregabalin (SMD=1.71±.13; 95% CI, 1.458–1.965; P<.001). A significant reduction in other SCI secondary conditions, including sleep interference (SMD=1.46±.12; 95% CI, 1.22–1.71; P<.001), anxiety (SMD=1.05±.12; 95% CI, .81–1.29; P<.001), and depression (SMD=1.22±.13; 95% CI, .967–1.481; P<.001) symptoms, was shown. A significantly higher risk of dizziness (risk ratio [RR]=2.02, P=.02), edema (RR=6.140, P=.04), and somnolence (RR=1.75, P=.01) was observed.

Conclusions

Gabapentin and pregabalin appear useful for treating pain and other secondary conditions after SCI. Effectiveness comparative to other analgesics has not been studied. Patients need to be monitored closely for side effects.     

HUCMSCs移植对大鼠亚急性脊髓损伤GAP-43和SPRR1A蛋白表达及神经功能的影响

[目的]探讨不同剂量的人脐带源性间充质干细胞(H UCMSCs)移植对大鼠亚急性脊髓损伤GAP-43和SPRR1A蛋白表达及神经功能的影响.[方法]92只SD大鼠分为五组:行全椎板切除、未建模、未移植12只(A组);建模后未移植干细胞20只(B组);建模后移植1×106个干细胞20只(C组)、建模后移植3×106个干细胞20只(D组)、建模后移植5×106个干细胞20只(E组).在C、D、E组移植术后d1、d7、d14、d21对五组进行运动功能评分,取损伤脊髓标本进行免疫组化检测GAP-43和SPRR1A蛋白表达,荧光显微镜观察干细胞在脊髓损伤区聚集迁徙情况.[结果]C、D、E组脊髓损伤区运动功能恢复和GAP-43、SPRR1A蛋白的阳性表达均显著高于A、B组,但D组、E组较C组显著增高,其差异均有统计学意义(P＜0.05);免疫荧光证实HUCMSCs在脊髓损伤区及其周围明显聚集并存活;BBB评分A组无变化,C、D、E组高于B组,D、E组高于C组,D组与E组无差异.[结论]HUCMSCs移植治疗亚急性期脊髓损伤,可促进脊髓损伤区域GAP-43及SPRR1A蛋白的高表达,改善大鼠的运动功能,选择3×106个干细胞作为静脉移植剂量经济高效.     

Electroencephalographic Predictors of Neuropathic Pain in Subacute Spinal Cord Injury

It is widely believed that cortical changes are a consequence of longstanding neuropathic pain (NP). In this article, we demonstrate that NP in individuals with subacute spinal cord injury (SCI) has characteristic electroencephalography markers (EEG) that precede the onset of pain. EEG was recorded in a relaxed state and during motor imagination tasks in 10 able-bodied participants and 31 patients with subacute SCI (11 with NP, 10 without NP, and 10 who had pain develop within 6 months of EEG recording). All 20 patients with SCI initially without NP were tested for mechanically induced allodynia, but only 1 patient, who later had pain develop, reported an unpleasant sensation. The EEG reactivity to eye opening was reduced in the alpha band and absent in the theta and beta bands in the patients who later developed pain and was reduced in those who already had pain. Alpha band power was reduced at BA7 in both the relaxed state and during motor imagination in patients who either had or later developed pain compared with those without pain. All SCI groups had reduced dominant alpha frequency and beta band power at BA7. EEG reactivity to eye opening and reduced spontaneous and induced alpha activity over the parietal cortex were predictors of future NP, as well as markers of existing NP.Clinical Trial Registration Number: NCT02178917