右美托咪定及舒芬太尼联合鞘内注射对CCI模型大鼠DRG神经元GABAA激活电流的作用

目的:探讨右美托咪定复合舒芬太尼鞘内注射对坐骨神经慢性缩窄性损伤(CCI)模型大鼠DRG神经元GABAA激活电流的作用。方法:鞘内置管成功的雄性SD大鼠50只,随机分成5组:假手术组(Sham组)、模型对照组(CCI组)、右美托咪定组(Dex组)、舒芬太尼组(Suf组)、右美托咪定+舒芬太尼组(DS组)。术后1～14天每天鞘内注射,Dex组注射右美托咪定(Dex)2μg/kg、Suf组注射舒芬太尼(Suf)1μg、DS组注射Dex 1μg/kg+Suf 0.5μg;各组药物总容量均配成20μL Sham组、CCI组注射等体积0.9%生理盐水。每组分别在术前、术后1、3、7、14天给药30 min后,测定机热痛阈(TWL)和械痛阈(MWT)。于术后第7天痛阈值测定后,提取大鼠L4、6节段脊髓(n=9),应用全细胞膜片钳技术检测大鼠背根神经GABA激活电流(IGABA)。结果:与Sham组相比,CCI组、Dex组、Suf组及DS组术后3、7、14天机械痛阈和热痛阈显著降低(P0.05);与CCI模型组相比,Dex组、Suf组及DS组在术后3、7、14天机械痛阈和热痛阈显著升高(P0.05);与DS组相比,Dex组及Suf组在术后3、7、14天TWL及MWT阈显著降低(P0.05)。术后7天与CCI模型组相比,Dex组、Suf组及DS组IGABA水平在显著增强(P0.05);与DS组相比,Dex组及Suf组IGABA水平显著减弱(P0.05)。结论:鞘内联合应用右美托咪定及舒芬太尼治疗神经病理性疼痛具有显著的协调镇痛作用,并且这种协同镇痛作用与调节GABA激活电流有关。     

糖尿病周围神经病变疼痛机制研究进展

痛性糖尿病周围神经病变（DPN）表现为对多数镇痛药物的抵抗。最近许多研究表明，背根神经节（DRG）钠离子通道、丝裂原激活蛋白激酶、一氧化氮、蛋白激酶C、去甲肾上腺素等在DPN疼痛信号转导和痛觉调制方面发挥重要作用。现就DPN疼痛的分子机制及治疗前景作一探讨。     

Efficacy of hyaluronic acid or steroid injections for the treatment of a rat model of rotator cuff injury

This study evaluated dorsal root ganglia from C3–C7, analyzed gait, and compared the expression of calcitonin gene‐related peptide (CGRP) which was a marker of inflammatory pain in a rat rotator cuff tear model in which the supraspinatus and infraspinatus tendons were detached; comparisons were made to a sham group in which only the tendons were exposed. Fluorogold was injected into the glenohumeral joint 21 days after surgery in both groups, and saline, steroids, or hyaluronic acid was injected into the glenohumeral joint in the rotator cuff tear group 26 days after surgery. The proportions of CGRP‐immunoreactive neurons were higher and the gait parameters were impaired in the rotator cuff tear group compared to in the sham group. However, the CGRP expression was reduced and the gait was improved with steroid or hyaluronic acid injection compared to saline, suggesting that both hyaluronic acid and steroid injections suppressed of inflammation which thought to be provided pain relief. While there were no significant differences, the suppression of CGRP expression and the improved gait after hyaluronic acid and steroid injections suggested that both methods were effective for rat rotator cuff tear model. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1861–1867, 2015.     

CaMK Ⅱ信号转导通路在病理性疼痛中的研究进展

背景 钙/钙调素依赖性蛋白激酶Ⅱ(Ca2+/calmodulin-dependent protein kinaseⅡ,CaMKⅡ)是一种多功能的丝氨酸苏氨酸蛋白激酶,广泛分布在周围和中枢神经系统.目的 有研究表明CaMKⅡ在感觉信息特别是伤害性信息的传入与整合中具有重要作用,为此现作一综述.内容 此文阐述了背根神经节(...     

椎间盘镜术中神经节给药对神经根炎性疼痛的作用

[目的]椎间盘镜下行腰椎间盘突出症手术时,对受累神经根的神经节行鞘内注药,观察其对术后早期疼痛及腰椎手术失败综合征的预防作用.[方法]2007年6月-2009年8月,腰椎间盘突出症患者161例.神经节给药组85例和对照组76例.在椎间盘镜下行腰椎间盘切除术过程中,试验组:向受累神经节鞘内打入1.5nl布比卡因和地寒米松混合液.对照组:神经节鞘内不注药.对两组患者术前,术后6、12h,l、3、7d,腰、臀部及双下肢疼痛及麻木情况行VAS视觉评分并评定受累神经根功能.在术后第6.12.24个月,采用腰椎术后疗效评定标准对术后各组患者远期疗效进行随访.[结果]两组患者在年龄、体重、性别等方面无显著性差异,两组术后神经功能恢复良好.统计学分析显示神经节给药组术后早期受累肢体的疼痛评分低于对照组,具有显著性差异(p＜0.05).提示神经节给药能有效控制术后疼痛;术后麻木改善程度经统计学分析没有显著性差别(P＞0.05).术后6、12、24个月疗效评定显示,两组统计学无显著性差异.[结论]椎间盘镜下神经节注射药物安全,能有效控制术后神经根炎性疼痛.     

CaMKⅡ信号转导通路在病理性疼痛中的研究进展

背景钙／钙调素依赖性蛋白激酶II（Ca2/almodulin—dependent protein kinaseⅡ,CaMKⅡ）是一种多功能的丝氨酸苏氨酸蛋白激酶,广泛分布在周围和中枢神经系统。目的有研究表明CaMKⅡ在感觉信息特别是伤害性信息的传人与整合中具有重要作用,为此现作一综述。内容此文阐述了背根神经节（dorsal root ganglion,DRG）、脊髓背角（Spinal dorsalhom,SDH）及脊髓上水平的、CaMK11在病理性疼痛的作用及其调节因素的研究进展。趋势CaMKⅡ可能为阐明疼痛机制提供依据,为临床治疗疼痛提供方向和思路。     

Low affinity NGF receptor (p75 neurotrophin receptor) inhibitory antibody reduces pain behavior and CGRP expression in DRG in the mouse sciatic nerve crush model

Nerve growth factor (NGF) and its low‐affinity receptor, p75 neurotrophin receptor (p75NTR), are important mediators of pain. To explore further the mechanisms involved, we examined suppression of pain behavior and expression of neuropeptides such as calcitonin gene‐related peptide (CGRP) using a p75 NTR inhibitory antibody, in a mouse sciatic nerve crush model. In the nerve‐injured model, 150 µg of a p75 NTR inhibitory antibody or 10 µl of saline were applied. The sciatic nerve in the sham‐operated group was uninjured. Mechanical allodynia was measured for 2 weeks. CGRP and p75NTR expression in L5 dorsal root ganglions (DRGs) was examined immunohistochemically. Mechanical allodynia was found in the two nerve injured groups, but not in the sham‐operated group (p < 0.05). However, the magnitude of the mechanical allodynia was significantly decreased after application of p75 NTR inhibitory antibody (p < 0.05). CGRP and p75NTR immunoreactivity in the L5 DRG neurons was upregulated in the injured nerve groups compared with the sham‐operated group; however, p75 NTR inhibitory antibody decreased the CGRP and p75NTR expression (p < 0.01). Application of the p75 NTR inhibitory antibody to the pinched sciatic nerve suppressed CGRP and p75NTR expression and pain behavior. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:279–283, 2010     

大鼠背根神经节γ氨基丁酸A受体在慢性神经痛中的作用

目的观察调控大鼠背根神经节(DRG)γ氨基丁酸A(GABA-A)受体的功能对神经痛动物痛阈的影响,探讨DRG GABA-A受体在神经痛发病机制中的作用。方法选用成年雌性SD大鼠50只,随机均分为五组,制作脊神经结扎模型,A组脊神经结扎术后立即于L5DRG局部运用蝇蕈醇20μg(50μl);B组予荷包牡丹碱0.15μg(50μl);C组给予蝇蕈醇20μg+荷包牡丹碱0.15μg;D组于脊神经结扎术后5dDRG局部注射蝇蕈醇20μg;E组注射生理盐水50μl。于术前1d至术后10d,每天行行为学检测大鼠术侧后爪机械痛阈和热痛阈。结果 L5脊神经结扎术后动物出现跛足,舔脚等神经痛症状。E组机械痛阈于术后1d开始下降,持续至术后10d,热痛阈于术后3d开始下降,持续至术后10d。与E组比较,A组术后各时点机械痛阈和热痛阈明显升高(P<0.05),B组术后1d机械痛阈和热痛阈即明显下降,并持续至术后10d(P<0.05),且明显低于E组(P<0.05)。D组术后6d,机械痛阈和热痛阈开始上升(P<0.05),于术后7d达到高峰,术后8d机械痛阈和热痛阈开始下降。结论 DRG GABA-A受体在神经痛的发生中起重要作用,激动GABA-A受体可以预防神经痛的发生,但对已经发生的神经痛只起到暂时缓解的作用。     

糖尿病大鼠膀胱和脊髓背根神经节中P75的表达与尿流动力学改变

目的探讨糖尿病大鼠膀胱与脊髓背根神经节（DRG）中神经生长因子受体P75的表达及尿流动力学改变。方法建立糖尿病大鼠模型20只，以15只正常大鼠为对照，应用免疫组化方法，分别检测大鼠膀胱组织及DRG中P75的变化情况，结合尿流动力学改变，探讨糖尿病膀胱病变（DC）可能的发病机制。结果与对照组比较，糖尿病组膀胱湿重增加[（171．150±6．081）vs（135．530±5．330）mg]，最大膀胱容量增加[（2．97±0．54）mLvs（1．73±0.23）mL]，储尿期膀胱压降低[（0．39±0．05）vs（0．77±0．06）kPa]，最大膀胱压力降低[（2．98±0．12）vs（5．99±0．25）kPa]（P均〈0．05）。无论是在膀胱组织还是在DRG中，糖尿病组P75的表达均低于对照组，有统计学意义（P〈0．05）。结论神经生长因子的受体P75在膀胱与脊髓背根神经节中的异常表达可能与DC的发病机制有关。     

糖尿病大鼠治疗后膀胱和腰骶背根神经节中神经生长因子的表达及超微结构研究

目的通过动物实验研究糖尿病大鼠治疗后膀胱和腰骶背根神经节中神经生长因子（NGF）的表达和超微结构变化及意义。方法参照Schmeichel等方法制备糖尿病大鼠模型,造模成功后4周应用NGF和胰岛素治疗4周,然后应用免疫组织化学方法检测大鼠膀胱和背根神经节中NGF的表达情况,利用透射电镜观察膀胱和腰骶背根神经节的超微结构变化。结果糖尿病大鼠经NGF和胰岛素治疗后膀胱和腰骶背根神经节中NGF的含量明显增加,差异有统计学意义（P〈0.05）,并且其形态学明显改善。结论 NGF的异常在糖尿病膀胱病变（DC）的发病中可能具有重要作用,给予外源性NGF可能有助于DC病变减轻和功能改善。     

鞘内注射KN93对神经病理性疼痛大鼠痛行为学的影响

目的 观察鞘内注射钙/钙调蛋白依赖性蛋白激酶Ⅱ(Ca2+/calmodulin dependent protein kinaseⅡ,CaMKⅡ)抑制剂KN93对腰背根神经节慢性压迫(chronic compression of dorsal root ganglion,CCD)大鼠神经病理性疼痛的影响. 方法 SD雄性大鼠48只,按随机数字表法分为3组:假手术组(S组,11只)、CCD模型组(C组,11只)、KN93组(K组,26只).C组、K组制备CCD模型,S组仅暴露L5-6椎间隙.术后14dS组和C组鞘内注射10％溶媒二甲基亚砜(dimethyl sulfoxide,DMSO)25μl,K组鞘内注射溶于10％DMSO的KN93 50 μg/25μl.各组在造模前1 d(t1),造模后4(t2)、7(t3)、10(t4)、14 d(t5)随机取8只大鼠检测热缩足反射潜伏期(paw withdrawal thermal latency,PWTL)和机械缩足反射阈值(paw withdrawal mechanical threshold,PWMT);并于鞘内注射DMSO或KN93后2(t6)、4(t7)、10(t8)、12(t9)、24 h(t10)时进行相同的行为学检测.各组于给药前以及K组的给药后各时间点(t6～t9)随机取3只大鼠处死并取脊髓腰膨大部分,采用Western blot方法检测CaMKⅡ蛋白表达水平.结果 鞘内给药后t6～t9时点,K组PWTL [(14.7±1.6)、(18.6±1.8)、(21.2±2.5)、(15.3±2.0)s],PWMT [(12.0±1.0)、(15.4±1.4)、(17.5±1.7)、(14.9±1.6)g]比C组PWTL[(11.6±1.8)、(10.7±1.7)、(11.7±2.4)、(9.9±1.7)s],PWMT[(8.4±0.9)、(9.6±1.6)、(10.6±1.7)、(8.9±1.3)g]升高,差异有统计学意义(P＜0.05).给药前及给药后t10时,K组PWTL、PWMT与C组比较,差异无统计学意义(P＞0.05).和t5时CaMKⅡ值(1.55±0.12)比较,给药后t6～t9时间点CaMKⅡ蛋白[(1.37±0.11),(1.15±0.12)、(0.75±0.08)、(0.86±0.12)]表达下降(P＜0.05). 结论 鞘内注射KN93可有效缓解神经病理性疼痛大鼠的疼痛反应.     

脉冲射频治疗颈源性头痛的新进展

脉冲射频治疗(PRF)是一种前沿的治疗慢性疼痛的新技术,具有创伤小、操作便捷等优点。近年来,脉冲射频(PRF)应用于颈源性头痛,取得较好的临床疗效。本文就脉冲射频治疗颈源性头痛的最新进展相关综述,以期提供临床参考。     

Altered expression of sodium channel distribution in the dorsal root ganglion after gradual elongation of rat sciatic nerves

To elucidate the pathophysiological mechanisms underlying chronic nerve‐stretch injury, we gradually lengthened rat femurs by 15 mm at the rate of 0.5 mm/day (group L, n = 13). The control groups comprised sham‐operated (group S, n = 10) and naive (group N, n = 8) rats. Immediately after the lengthening, we performed a conduction study on their sciatic nerves and harvested samples. Electrophysiological and histological analyses showed mild conduction slowing and axonal degeneration of unmyelinated fibers in group L rats. Altered mRNA expression of the voltage‐gated sodium channels in the dorsal root ganglion was also observed. Tetrodotoxin‐resistant (TTX‐R) sodium‐channel Nav1.8 mRNA expression was significantly decreased and TTX‐R sodium‐channel Nav1.9 mRNA expression showed a tendency to decrease when compared with the mRNA expressions in the control groups. However, tetrodotoxin‐sensitive (TTX‐S) sodium‐channel Nav1.3 mRNA expression remained unaltered. The immunohistochemical alteration of Nav1.8 protein expression was parallel to the results of the mRNA expression. Previous studies involving neuropathic states have suggested that pain/paresthesia is modulated by a subset of sodium channels, including downregulation and/or upregulation of TTX‐R and TTX‐S sodium channels, respectively. Our findings indicate that Nav1.8 downregulation may be one of the pathophysiological mechanisms involved in limb lengthening‐induced neuropathy. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:481–486, 2010     

化学去细胞异体神经促神经再生的体外实验研究

[目的]对大鼠化学去细胞异体神经蛋白成分进行电泳分析,观察去细胞异体神经中的蛋白组分;制备去细胞神经薄膜,接种背根神经节,观察其结构对神经生长的影响。[方法]按Sondell法制备大鼠的去细胞异体神经,将制备好的神经进行电泳分析,观察28～30 kDa区域的髓鞘蛋白的去除程度;将制备的神经进行冰冻切片,接种鸡胚背根神经,进行神经纤维荧光染色,观察神经纤维在神经切片上的生长方向。[结果]去细胞异体神经电泳结果显示:28～30 kDa区域髓鞘蛋白完全消失,化学萃取的去细胞神经可以完全去除髓鞘蛋白;背根神经节发出大量的神经纤维沿着去细胞神经基底膜管方向生长。[结论]去细胞异体神经中无残留引起免疫反应的髓鞘蛋白,保留的基底膜管结构对促神经纤维再生具有引导性作用。     

TMEM16A下调缓解坐骨神经分支选择性损伤大鼠的神经病理性痛

目的探讨TMEM16A在坐骨神经分支选择性损伤(SNI)神经病理性痛模型大鼠中的作用。方法成年雄性SD大鼠,体重180～220 g,随机分为假手术组(sham组,n=6)和SNI组(n=12),sham组大鼠仅暴露左侧坐骨神经分支;SNI组行SNI。在术前1 d、术后3、7、10、14 d测定大鼠热缩足潜伏期(TWL)、冷缩足潜伏期(CWL)和机械缩足阈值(MWT)。采用Western blot测定术前1 d和术后7、14 d术侧背根神经节(DRG)中TMEM16A蛋白含量。另取72只雄性SD大鼠随机分为四组:sham+生理盐水组(CS组)、SNI+生理盐水组(SS组)、SNI+CaCCinh-A01组(SC组)和SNI+T16Ainh-A01组(ST组),每组18只。在给药前3 d行鞘内置管术,CS、SS组大鼠术后14 d鞘内单次注射生理盐水10μl,SC、ST组大鼠相同时点鞘内单次注射10μl浓度为1 mg/ml的特异性钙激活氯通道(CaCCs)抑制剂CaCCinh-A01或T16Ainh-A01,在给药后的8 h内每隔1 h测定TWL、CWL和MWT。另设相同四组大鼠于术后第12天开始每隔6 h分别鞘内注射10μl的生理盐水、CaCCinh-A01或T16Ainh-A01,共注射5次,于术后第14天提取术侧DRG进行Western blot和免疫荧光实验,观察TMEM16A蛋白含量及TMEM16A分布特点。结果与sham组比较,SNI组术后3、7、10、14 d CWL明显延长(P0.05),MWT明显降低(P0.05),TWL差异无统计学意义。与术前1 d比较,SNI组TMEM16A蛋白含量在术后7、14 d明显增高,且术后14 d明显高于术后7 d(P0.05)。与SS组比较,SC组和ST组CWL从给药后1 h开始降低,3 h达到最低,且在给药后的1～4 h内SC组CWL明显小于ST组(P0.05);MWT从给药后1 h开始升高,分别在2 h和3 h达到最高且在给药后的1、2、4、7和8 h内SC组MWT明显高于ST组(P0.05);TWL在各时点差异均无统计学意义。与SS组比较,SC组和ST组TMEM16A蛋白含量明显降低(P0.05),且ST组明显低于SC组(P0.05)。免疫荧光结果显示TMEM16A主要表达在与伤害感受相关的中小神经元上。结论 TMEM16A可能在SNI诱导的持续性痛觉过敏中起关键作用。TMEM16A可为神经病理性痛提供新的药物靶点。