代谢性谷氨酸受体亚型5对骨癌痛小鼠痛行为及脊髓水平炎症反应的影响

目的:探讨鞘内注射mGluR5拮抗剂MTEP对骨癌痛小鼠热痛觉过敏及脊髓水平IL-1β、IL-6、TNF-α表达的影响。方法:C3H/HeNCrlVr雄性小鼠60只,随机分为:①MTEP+Tumor组:癌痛组从第14 d开始鞘内注射MTEP150nmol,qd,共7次;②生理盐水+Tumor组:以等体积的生理盐水代替MTEP;③MTEP+Sham组:用等剂量MTEP给予假手术组;④生理盐水+Sham组:用等体积的生理盐水给予假手术组;⑤正常组:正常饲养21d。应用热辐射刺激仪测定缩足潜伏期(PWL)。应用Real-time PCR技术检测mRNA表达。结果:各组小鼠术前基础PWL差异无统计学意义(P>0.05)。术后14 d,与正常组相比,骨癌痛组PWL明显降低(P<0.05),假手术组PWL差异无统计学意义(P>0.05)。术后21 d,和正常组相比,MTEP+Sham组、生理盐水+Sham组PWL和脊髓IL-1β、IL-6、TNF-α表达差异均无统计学意义(P>0.05);生理盐水+Tumor组PWL(6.18±1.29)s明显低于正常组(15.91±1.65)s(P<0.05),脊髓IL-1β、IL-6、TNF-α表达则高于正常组;MTEP+Tumor组(9.39±1.94)s PWL高于生理盐水+Tumor组,脊髓IL-1β、IL-6、TNF-α表达则低于生理盐水+Tumor组(P<0.05)。结论:鞘内注射mGluR5拮抗剂抑制脊髓水平表达释放炎症因子IL-1β、IL-6和TNF-α可能是其抗癌痛作用机制之一。     

CORRELATION OF N30 SOMATOSENSORY EVOKED POTENTIALS WITH SPASTICITY AND NEUROLOGICAL FUNCTION AFTER STROKE: A CROSS-SECTIONAL STUDY

ObjectiveTo test whether the presence of N30 somatosensory evoked potentials, generated from the supplementary motor area and premotor cortex, correlate with post-stroke spasticity, motor deficits, or motor recovery stage.DesignA cross-sectional study.PatientsA total of 43 patients with stroke hospitalized at Maoming People’s Hospital, Maoming, China.MethodsForty-three stroke patients underwent neurofunctional tests, including Modified Ashworth Scale (MAS), Brunnstrom stage, manual muscle test and neurophysiological tests, including N30 somatosensory evoked potentials, N20 somatosensory evoked potentials, motor evoked potentials, H-reflex. The results were compared between groups. Correlation and regression analyses were performed as well. Results: Patients with absence of N30 somatosensory evoked potential exhibited stronger flexor carpi radialis muscle spasticity (r = –0.50, p < 0.05) and worse motor function (r = 0.57, p < 0.05) than patients with presence of N30 somatosensory evoked potential. The generalized linear model (GLM) including both N30 somatosensory evoked potentials and motor evoked potentials (Akaike Information Criterion (AIC) = 121.99) better reflected the recovery stage of the affected proximal upper limb than the models including N30 somatosensory evoked potentials (AIC = 125.06) or motor evoked potentials alone (AIC = 127.45).ConclusionN30 somatosensory evoked potential status correlates with the degrees of spasticity and motor function of stroke patients. The results showed that N30 somatosensory evoked potentials hold promise as a biomarker for the development of spasticity and the recovery of proximal limbs.LAY ABSTRACTImpair motor function and spasticity adversely affect the ability to conduct the activities of daily life. Somatosensory evoked potentials and motor evoked potentials are essential to differential evaluation of degree of post-stroke spasticity and stage of motor recovery. This is the first study of the correlations between somatosensory evoked potentials N30, components of somatosensory evoked potentials related to the supplementary motor area and dorsolateral premotor cortex combined with motor evoked potentials and motor function. The results indicate that the N30 somatosensory evoked potential status is correlated with the degrees of spasticity and motor function of stroke patients. The conclusion showed that N30 Somatosensory evoked potentials hold promise as a biomarker for the development of spasticity and the recovery of proximal limbsKey words: stroke, hemiparesis, spasticity, N30 somatosensory evoked potential, motor evoked potential, function recovery

Stroke is the leading cause of disability worldwide (1). Most patients with stroke experience motor deficits, which impair motor function and adversely affect their ability to perform activities of daily living (ADL). Spasticity, one of the motor deficits that appears after stroke, is accompanied by an increased risk of falling and resulting fractures, and is associated with increased morbidity and mortality (2). Both post-stroke recovery and the development of spasticity are associated with neural plasticity of different anatomical regions, such as the reticulospinal tracts, supplementary motor area (SMA) and dorsolateral premotor cortex (PMC) (3–5).Precise biomarkers of motor function are critical for early intervention. The identification of somatosensory evoked potentials (SEPs) is essential for the accurate diagnosis of patients with focal brain disorders, and SEP components reflect the activities of different neural structures (6). N30 SEPs are somatosensory evoked potential components. Anatomically, N30 SEPs are generated from the SMA and PMC (7), from which the corticoreticular tracts radiate (8–10). Pathophysiologically, N30 SEPs present apparent inhibition in individuals with other myotonic disorders (11). Continuous theta burst stimulation of the SMA reduces the amplitude of the N30 (12). Moreover, SMA impairment leads to myodystonia and is closely associated with motor outcomes (13, 14).Thus, it was hypothesized that the presence of N30 SEPs is related to the degree of spasticity and functional status in people with stroke. The aims of the study were to test: (i) whether the presence of N30 SEPs correlates with post-stroke spasticity (PSS), motor deficits and stage of motor recovery; and (ii) whether the combination of N30 SEPs and motor evoked potentials (MEPs) can be used for the differential evaluation of degree of PSS and stage of motor recovery.     

羟考酮注射液联合帕瑞昔布钠治疗瑞芬太尼复合麻醉术后疼痛的疗效观察

目的:观察盐酸羟考酮注射液联合帕瑞昔布钠治疗瑞芬太尼全麻后痛觉过敏的疗效及不良反应情况。方法:选择下腹部手术患者60例,随机分为三组:低剂量羟考酮组(Q1)、高剂量羟考酮组(Q2)和羟考酮联合帕瑞昔布钠组(Q+P),每组20例。分别于手术结束前30 min静脉注射羟考酮0.10 mg/kg,羟考酮0.15 mg/kg和羟考酮0.10 mg/kg+帕瑞昔布钠40 mg,观察并记录三组患者停药后苏醒时间、拔管时间、术后疼痛视觉模拟评分(visual analogue scale,VAS)、警觉/镇静评分(alertness/sedation score,OAA/S)、苏醒期躁动(emergence agitation,EA)、药物不良反应(呼吸抑制、恶心呕吐)。结果:三组患者一般资料无统计学差异,Q1组和Q+P组患者的苏醒时间和拔管时间比Q2组短,差异有统计学意义(P<0.05)。Q1组和Q+P组患者OAA/S评分高于Q2组,嗜睡发生率低于Q2组(P<0.05)。在术后疼痛、躁动评分方面Q2组和Q+P组优于Q1组(P<0.05)。结论:手术结束前30 min给予羟考酮注射液联合帕瑞昔布钠可有效的预防瑞芬太尼所引起的痛觉过敏反应,且不良反应少。     

牛痘疫苗接种家兔炎症皮肤提取物治疗脊髓损伤后神经病理性疼痛的定量感觉检查研究

目的:分析脊髓损伤(spinal cord injury,SCI)后神经病理性疼痛患者损伤平面的皮肤感觉阈值变化与差异,推测牛痘疫苗接种家兔炎症皮肤提取物(神经妥乐平)治疗SCI后神经病理性疼痛的作用机制。方法:39例SCI患者根据神经病理性疼痛的视觉模拟量表评分及使用神经妥乐平的不同情况分为轻、中、重3组,应用定量感觉检查(Quantitative sensory testing,QST)的方法,测试损伤平面皮肤的单丝触觉、冷觉阈值、热觉阈值以及冷痛觉阈值、热痛觉阈值,并与20例正常健康者进行比较。结果:与正常健康者相比,SCI患者损伤平面的单丝触觉阈、热觉阈均明显提高,冷觉阈明显降低。与无明显疼痛者比较,中、重度神经病理性疼痛者的单丝触觉阈、冷痛阈和热痛阈值间的差异存在统计学意义;神经妥乐平治疗有效者与无效者比较,冷痛阈、热痛阈间差异均存在统计学意义。结论:神经妥乐平治疗SCI后的神经病理性疼痛具有其特定的解剖生理学基础。通过QST筛查,有利于对SCI后的神经病理性疼痛进行早期干预。     

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。     

银质针导热治疗对MPS大鼠脊髓中枢神经递质的影响

目的:观察银质针导热疗法对肌筋膜疼痛综合征大鼠脊髓水平神经递质的影响。方法:24只健康SD大鼠随机分为3组(n=8):正常组,不给予任何刺激;模型组,采用打击结合运动疲劳建立慢性肌筋膜疼痛综合征模型;银质针组,MPS模型成功后,行银质针导热治疗。各组大鼠在治疗2周后测定热痛阈值、右股内侧肌自发电活动。麻醉后处死大鼠,取右股内侧肌及脊髓L4~6节段,HE染色切片观察局部肌肉形态学变化,免疫组化法检测脊髓神经元型一氧化氮合酶(n NOS)、P物质(SP)及5-羟色胺(5-HT)。结果:与正常组相比模型组大鼠热痛阈降低,局部肌肉自发电活动增加(P<0.01);脊髓n NOS、SP表达升高(P<0.01)。与模型组相比,银质针组热痛阈明显升高,自发电活动明显降低(P<0.01);脊髓n NOS及SP表达明显降低,5-HT表达明显升高(P<0.01)。结论:银质针导热治疗可能通过降低肌筋膜疼痛综合征大鼠脊髓n NOS及SP表达,增高5-HT表达产生镇痛作用。