低频电针对脊神经结扎大鼠痛敏化的干预作用

目的观察低频电针对脊神经结扎神经病理痛大鼠模型痛敏化的干预作用,探讨其可能的外周痛敏化调节机制。方法建立大鼠L5脊神经结扎模型,电针足三里和昆仑穴,观察大鼠痛觉超敏反应,运用Western blotting 法检测L4、L5背根神经节(DRG)辣椒素受体(TRPV1)与P 物质(SP)水平,采用TRPV1 激动剂6'-IRTX进行验证。结果脊神经结扎大鼠出现明显的痛敏化反应,术侧L4 DRG TRPV1 和L5 DRG SP 水平升高(P<0.05);低频电针能减轻模型大鼠的痛敏反应,抑制TRPV1、SP 水平上升(P<0.05)。6'-IRTX腹腔注射能拮抗低频电针的抗痛敏化作用。结论低频电针可减轻痛敏化,发挥对神经病理痛的治疗作用,其机制可能与其有效调控DRG TRPV1 和SP有关。     

新生时辣椒素处理大鼠的炎症和痛敏：对脊髓背角伤害性神经元的影响

新生时辣椒素处理大鼠的炎症和痛敏──对脊髓背角伤害性神经元的影响已知，脊髓中有两类伤害性神经元：一类是伤害特异性（ＮＳ）神经元，只对伤害性刺激起反应，接受Ｃ纤维和Ａδ纤维的传入冲动；另一类是广动力范围（ＷＤＲ）神经元，对伤害性和非伤害性刺激均起反应，...     

电针对糖尿病神经痛模型大鼠脊髓背角p-ERK和p-CREB的影响

目的 观察电针对糖尿病神经痛大鼠脊髓背角磷酸化细胞外信号调节蛋白激酶（p-ERK1/2）和磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）表达的影响。 方法 从30只健康雄性SD大鼠中随机选择8只作为正常组,其余22只采用单次大剂量腹腔注射链脲佐菌素法建立糖尿病神经痛模型,共16只大鼠造模成功,将其分为模型组和电针组,每组8只。电针组于链脲佐菌素注射后15 d开始电针干预,每日1次,每次30 min,干预1周,穴位选择双侧“后三里”和“昆仑”穴。链脲佐菌素注射前、注射后7 d、14 d、21 d,观察并记录大鼠的体重、空腹血糖、热痛阈变化,采用免疫印迹法检测大鼠脊髓背角p-ERK1/2和p-CREB表达,采用免疫荧光法检测p-CREB阳性细胞数与神经元共表达情况。 结果 链脲佐菌素注射后7 d、14 d、21 d,与正常组比较,模型组大鼠体重下降（P<0.05）、空腹血糖升高（P<0.015）。链脲佐菌素注射后7 d,与正常组比较,模型组大鼠热痛阈无显著变化;链脲佐菌素注射后14 d、21 d,模型组大鼠热痛阈下降（P<0.05）。与模型组比较,链脲佐菌素注射后21 d,电针组大鼠热痛阈显著升高（P<0.05）。免疫印迹结果显示,与正常组比较,模型组大鼠脊髓背角p-ERK1/2和p-CREB蛋白表达显著升高（P<0.05）;与模型组比较,电针组大鼠脊髓背角p-ERK1/2和p-CREB蛋白表达显著降低（P<0.05）。免疫荧光结果显示,与正常组比较,模型组大鼠脊髓背角p-CREB阳性细胞数升高（P<0.05）;与模型组比较,电针组大鼠脊髓背角p-CREB阳性细胞数降低（P<0.05）;糖尿病神经痛模型大鼠脊髓背角p-CREB与神经元存在共表达。 结论 电针可有效缓解糖尿病神经痛,其机制可能与抑制大鼠脊髓背角p-ERK1/2和p-CREB的蛋白表达有关。     

ACTH及电针对甲醛痛敏大鼠脊髓NOS阳性神经元增多的影响

本文采用ＮＡＤＰＨ－ｄ组化染色技术,研究鞘内注射（ｉ．ｔ．）ＡＣＴＨ及电针刺激（ＥＡ）对甲醛痛敏大鼠脊髓背角浅层ＮＯＳ阳性神经元增多的影响。结果显示ＡＣＴＨ（０．５Ｕ,ｉ．ｔ．）及电针（１ｍＡ５０Ｈｚ,５ｍＡ５Ｈｚ,１ｍＡ５Ｈｚ）刺激“夹脊穴”３０ｍｉｎ均可显著抑制脊髓背角浅层ＮＯＳ阳性神经元增多;ｉ．ｔ．ＡＣＴＨ（０．５Ｕ）和电针刺激（１ｍＡ５Ｈｚ）同时给予时,抑制作用显著增加;ｉ．ｔ．ＮＯ前体     

低频电针对脊髓损伤致急性自发痛模型大鼠急性痛超敏的影响

目的：观察低频电针对脊髓损伤致急性自发痛模型大鼠急性痛超敏和自发痛行为学的影响。方法： 60只SD大鼠随机均分为对照组,模型组及低、中、高频电针组,每组12只。模型组和低、中、高频电针组建 立急性脊髓 L2节段损伤模型。低、中、高频电针组分别用低频（2 Hz）、中频（50 Hz）、高频（100 Hz）电刺激 T8～T12节段夹脊穴和双侧“昆仑”和“足三里”,25 min/次,1 次/d,共14 d。治疗结束后,观察各组大鼠自发疼 痛行为,用足底热辐射测痛仪检测各组大鼠热缩足潜伏期（PWL）和50%机械性缩足阈值（PWT）;记录L1段 体感诱发电位（SEP）潜伏期及N波、P波的波幅。结果：与对照组相比,模型组的自发疼痛行为学动作的发 生次数增多（P＜0.05）;痛阈值降低（均P＜0.05）,急性痛超敏发生率增高（P＜0.05）,PWL和PWT降低（均 P＜0.05）,SEP潜伏期及N波、P波波幅均增加（均P＜0.05）。与模型组相比,3个电针组的自发疼痛行为学 动作的发生次数降低（均 P＜0.05）,痛阈值升高（均 P＜0.05）,急性痛超敏发生率降低（P＜0.05）,PWL 和 PWT降低（均P＜0.05）,SEP潜伏期及N波、P波波幅降低均P＜0.05）,且低频电针组的疗效优于中、高频电 针组（均P＜0.05）。结论：低频电针可提高脊髓损伤大鼠的痛阈,减轻急性自发痛超敏,改善自发痛引起的 行为学变化。     

脊神经结扎诱导神经病理痛大鼠脊髓背角BDNF的含量和表达上调

目的:研究脊神经结扎(SNL)大鼠脊髓背角BDNF的含量和蛋白表达的变化,并探讨其在神经病理痛形成中的作用.方法:按照双盲随机的原则,将30只雄性SD大鼠随机分为SNL手术组和假手术对照组,每组各15只大鼠,进行酶联免疫吸附实验(ELISA)和免疫组化染色,检测神经病理痛大鼠脊髓背角BDNF的含量和蛋白表达随时间的变化.结果:(1)ELISA定量分析显示,脊神经结扎可以显著上调脊髓背角BDNF的含量.SNL后,背角BDNF的含量在24 h内即可由手术前的(91.09±7.1)pg/mg总蛋白上升到(160.75±15.0)pg/mg总蛋白(P<0.01),这种上调的高峰可以持续到SNL后的48 h;然而在假手术大鼠,背角BDNF的含量则没有明显的变化.与假手术组相比,SNL大鼠背角BDNF上调的高峰期在24～48 h(P<0.01),此后其含量开始逐渐恢复,至SNL后28 d基本恢复至术前对照水平(P0.05);(2)免疫组化染色显示,在脊神经结扎的24h内,SNL大鼠结扎侧背角BDNF的蛋白表达也呈现明显的时间依赖性上调变化.SNL后12 h,背角浅层BDNF免疫反应的平均光密度值即可由手术前的0.18±0.01上调到0.25±0.03(P<0.05).与假手术组相比,在SNL后的12 h和24 h,SNL大鼠结扎侧背角浅层BDNF的免疫反应较假手术大鼠也明显上调,其平均光密度值分别由假手术大鼠的0.19±0.02和0.18±0.01上调到0.25±0.03(P<0.05)和0.23±0.01(P<0.05).结论:脊神经结扎可以呈时间依赖性的上调脊髓背角BDNF的含量和蛋白表达,这种上调的BDNF可能在外周神经损伤所引起的神经病理痛的早期发挥作用.     

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.     

蛋白激酶C对内脏炎症痛模型大鼠脊髓背角神经元电活动的影响

目的：本实验采用福尔马林诱导的急性内脏炎症痛模型，观察蛋白激酶C（Protein Kinase C，PKC）激动剂PMA（phorbol 12-myristate 13-acetate）与抑制剂H-7（1-（5-isoquinolinesulfonyl）2-meth-ylpiperazine dihydrochloride）对脊髓背角神经元放电的影响。方法：选用健康成年Wistar大鼠，随机分为4组：（1）福尔马林直肠粘膜下注射致炎组（F）；（2）福尔马林致炎与脊髓微透析生理盐水组（F＋NS）；（3）福尔马林致炎与脊髓微透析H-7组（F＋H-7）；（4）福尔马林致炎与脊髓微透析PMA组（F＋PMA）。结果：记录到24个单位的反应结果表明：福尔马林致炎后0～120min内放电频率明显增加，特别是0～15min和15～30min内与致炎前相比均有显著性增强（P＜0．05）；经微透析PMA和H-7后，上述时间段内放电频率分别明显增强（P＜0．01）和回降（P＜0．05）。结论：PKC在福尔马林致内脏炎症痛的产生和维持中起重要作用。     

蛛网膜下腔应用Ro 25-6981对神经病理痛大鼠的镇痛作用及其电生理学机制研究

目的:研究蛛网膜下腔应用Ro 25-6981,一种选择性的NMDA受体NR2B亚基(NR2B)的拮抗剂,对神经病理痛大鼠的镇痛作用及其可能的机制。方法:(1)雄性SD大鼠蛛网膜下腔置管,手术成功后进行L5脊神经结扎(SNL)手术。术后7天用vonFrey纤维丝测定机械痛敏,筛选出造模成功的SNL神经病理痛大鼠,随机分为三组,通过蛛网膜下腔插管分别鞘内给予(i.t.)Ro25-698110.0μg(20μl)、100.0μg(20μl),或等体积的生理盐水作对照。在给药后第30min、60min、90min和120min测定大鼠后爪的50%缩足阈值(PWT)及鞘内给药前后大鼠的运动功能。(2)通过在体细胞外记录的电生理学方法,观察脊髓背表面给予Ro 25-6981100.0μg对大鼠脊髓背角广动力范围(WDR)神经元放电的影响。结果:(1)与生理盐水组相比,鞘内应用Ro 25-698110.0μg对SNL大鼠的50%PWT和机械痛敏翻转百分率(%MPE)没有明显的影响(P>0.05,n=8),而100.0μg却能显著增加SNL大鼠的50%PWT和%MPE,起到明显的镇痛作用(P<0.05,n=8),并且在上述两种剂量下鞘内给药前后,动物的运动功能没有出现显著改变(P>0.05);(2)与生理盐水组相比,脊髓背表面给予Ro 25-6981100.0μg对WDR神经元的Aβ纤维诱发放电没有显著影响(P>0.05,n=6),但是可以显著抑制C纤维诱发放电(P<0.05,n=6)。结论:鞘内应用选择性的NR2B拮抗剂Ro 25-6981100.0μg可以对SNL大鼠产生明显的镇痛作用,而不影响动物的运动功能;这种镇痛作用可能是通过拮抗脊髓背角的NMDA受体NR2B亚基,进而抑制WDR神经元的C纤维诱发放电所产生的。     

cAMP-PKA信号通路介导大鼠骨癌痛的产生和维持

目的:探讨c AMP-PKA信号通路在大鼠骨癌痛发生发展中的作用。方法:雌性SD大鼠52只,随机分为5组:正常组(n=8),假手术组(n=8),骨癌痛组(n=12),骨癌痛+生理盐水组(n=8)和骨癌痛+PKA抑制剂组(n=16)。各组于造模前3天、1天以及造模后1、3、5、7、10、14天分别测定热缩足阈值和机械缩足阈值。PKA抑制剂Rp-c AMPS(1 mmol/20μl)分别于造模后早期(3、4、5天)和造模后后期(7、8、9天)经鞘内注射(每天1次)。采用酶联免疫吸附法(ELISA)检测大鼠背根神经节(DRG)和脊髓中c AMP的浓度和PKA的活性。结果:造模后,大鼠DRG和脊髓中c AMP的浓度显著增高,PKA的活性明显增强,与假手术组相比,差异有统计学意义(P<0.01)。早期和后期给予PKA抑制剂Rp-c AMPS治疗,均能显著延迟或抑制骨癌诱发的热痛敏和机械痛敏(P<0.01)。结论:骨癌显著增强DRG和脊髓中c AMP-PKA信号通路的活性,该信号通路的异常活动在骨癌痛的产生和维持中起着重要作用,抑制该信号通路的激活能有效减轻骨癌痛。     

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。     

Referred sensations and neuropathic pain following spinal cord injury

It has been proposed that painful and non-painful referred sensations (RSs) are associated with reorganization of sensory pathways in patients with complete spinal cord injury (SCI). In order to investigate the referred sensation (RS) phenomenon and its correlation with neuropathic pain (NP) 48 patients with complete SCI, 24 with chronic NP and 24 without pain or paraesthesias were studied using clinical examination and neurophysiological tests. Patients reporting RSs were re-examined at 2 and 10 weeks after the first examination. We defined the presence of RS as sensations perceived below the injury level in response to touch and pinprick stimuli in various body points above the injury level. The examination was carried out by one researcher applying the stimuli to the patient under two visual conditions (open and closed eyes), and then asking the patient to make tactile self-stimulation. Seven patients with SCI and NP (29%) reported RS below the injury level. RS were well located and consistently evoked at repeated examinations. Touch and pinprick stimulation elicited similar RS that were non-painful in six patients and painful in one. Visual feedback did not change RS perception and characteristics. None of the patients in the SCI group without NP presented RS. In conclusion, our results indicate that RS is relatively frequent in patients with complete SCI and NP. The common occurrence of RS in patients with NP and the location of the sensations in the same area as NP suggest that pain and RS share common pathophysiological mechanisms.     

Functional MRI of the brain detects neuropathic pain in experimental spinal cord injury

Functional magnetic resonance imaging (fMRI) has been used to map cerebral activations related to nociceptive stimuli in rodents. Here, we used fMRI to investigate abnormally increased responses to noxious or innocuous stimuli, in a well-established rat model of chronic neuropathic pain induced by photochemical lumbar spinal cord injury. In this model, a subpopulation of rats exhibits allodynia-like hypersensitivity to mechanical and cold stimulation of the trunk area. In those rats that do not develop overt hypersensitivity after identical spinal cord injury (i.e. non-hypersensitive rats), touch evoked pain can be triggered by the opioid receptor antagonist, naloxone. We show that cerebral activations in contralateral primary somatosensory cortex (SI) are markedly correlated with different behavioural characteristics of these animals. Identical electrical stimulation, applied on trunks of spinally injured hypersensitive and non-hypersensitive rats, evoked significantly higher responses in SI of the former than the latter. Although levels of fMRI signals in SI of the trunk territory were not significantly different between normal and spinally injured non-hypersensitive rats, the administration of naloxone significantly increased fMRI signals in the non-hypersensitive rats, but not in the normal rats. We conclude that increased activation of contralateral SI is a key feature of behavioural neuropathic pain in spinally injured rats and that fMRI is an effective method to monitor experimental neuropathic pain in small animals.     

Thalamic activity and biochemical changes in individuals with neuropathic pain after spinal cord injury

There is increasing evidence relating thalamic changes to the generation and/or maintenance of neuropathic pain. We have recently reported that neuropathic orofacial pain is associated with altered thalamic anatomy, biochemistry, and activity, which may result in disturbed thalamocortical oscillatory circuits. Despite this evidence, it is possible that these thalamic changes are not responsible for the presence of pain per se, but result as a consequence of the injury. To clarify this subject, we compared brain activity and biochemistry in 12 people with below-level neuropathic pain after complete thoracic spinal cord injury with 11 people with similar injuries and no neuropathic pain and 21 age- and gender-matched healthy control subjects. Quantitative arterial spinal labelling was used to measure thalamic activity, and magnetic resonance spectroscopy was used to determine changes in neuronal variability quantifying N-acetylaspartate and alterations in inhibitory function quantifying gamma amino butyric acid. This study revealed that the presence of neuropathic pain is associated with significant changes in thalamic biochemistry and neuronal activity. More specifically, the presence of neuropathic pain after spinal cord injury is associated with significant reductions in thalamic N-acetylaspartate, gamma amino butyric acid content, and blood flow in the region of the thalamic reticular nucleus. Spinal cord injury on its own did not account for these changes. These findings support the hypothesis that neuropathic pain is associated with altered thalamic structure and function, which may disturb central processing and play a key role in the experience of neuropathic pain.     

Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury

Sigma-1 receptor (σ₁R) is expressed in key CNS areas involved in nociceptive processing but only limited information is available about its functional role. In the present study we investigated the relevance of σ₁R in modulating nerve injury-evoked pain. For this purpose, wild-type mice and mice lacking the σ₁R gene were exposed to partial sciatic nerve ligation and neuropathic pain-related behaviors were investigated. To explore underlying mechanisms, spinal processing of repetitive nociceptive stimulation and expression of extracellular signal-regulated kinase (ERK) were also investigated. Sensitivity to noxious heat of homozygous σ₁R knockout mice did not differ from wild-type mice. Baseline values obtained in σ₁R knockout mice before nerve injury in the plantar, cold-plate and von Frey tests were also indistinguishable from those obtained in wild-type mice. However, cold and mechanical allodynia did not develop in σ₁R null mice exposed to partial sciatic nerve injury. Using isolated spinal cords we found that mice lacking σ₁R showed reduced wind-up responses respect to wild-type mice, as evidenced by a reduced number of action potentials induced by trains of C-fiber intensity stimuli. In addition, in contrast to wild-type mice, σ₁R knockout mice did not show increased phosphorylation of ERK in the spinal cord after sciatic nerve injury. Both wind-up and ERK activation have been related to mechanisms of spinal cord sensitization. Our findings identify σ₁R as a constituent of the mechanisms modulating activity-induced sensitization in pain pathways and point to σ₁R as a new potential target for drugs designed to alleviate neuropathic pain.     

Early transcutaneous electrical nerve stimulation reduces hyperalgesia and decreases activation of spinal glial cells in mice with neuropathic pain

Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (P < 0.05). In contrast, the application of TENS at 1 week (TENS-1w) or 2 weeks (TENS-2w) after injury was ineffective in reducing hyperalgesia (mechanical and thermal) or activation of microglia and astrocytes. Early TENS decreased p-p38 within microglia (P < 0.05), the expression levels of protein kinase C (PKC-γ), and phosphorylated anti-phospho-cyclic AMP response element-binding protein (p-CREB) in the superficial spinal dorsal horn neurons (P < 0.05), mitogen-activated protein (MAP) kinases, and proinflammatory cytokines, and increased the expression levels of opioid receptors (P < 0.05). The results suggested that the application of early TENS relieved hyperalgesia in our mouse model of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-γ, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible.     

Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states

Spinal cord injury (SCI) commonly results in the development of neuropathic pain, which can dramatically impair the quality of life for SCI patients. SCI-induced neuropathic pain can be manifested as both tactile allodynia (a painful sensation to a non-noxious stimulus) and hyperalgesia (an enhanced sensation to a painful stimulus). The mechanisms underlying these pain states are poorly understood. Clinical studies have shown that gabapentin, a drug that binds to the voltage-gated calcium channel alpha-2-delta-1 subunit (Ca_vα2δ-1) proteins is effective in the management of SCI-induced neuropathic pain. Accordingly, we hypothesized that tactile allodynia post SCI is mediated by an upregulation of Ca_vα2δ-1 in dorsal spinal cord. To test this hypothesis, we examined whether SCI-induced dysregulation of spinal Ca_vα2δ-1 plays a contributory role in below-level allodynia development in a rat spinal T9 contusion injury model. We found that Ca_vα2δ-1 expression levels were significantly increased in L4-6 dorsal, but not ventral, spinal cord of SCI rats that correlated with tactile allodynia development in the hind paw plantar surface. Furthermore, both intrathecal gabapentin treatment and blocking SCI-induced Ca_vα2δ-1 protein upregulation by intrathecal Ca_vα2δ-1 antisense oligodeoxynucleotides could reverse tactile allodynia in SCI rats. These findings support that SCI-induced Ca_vα2δ-1 upregulation in spinal dorsal horn is a key component in mediating below-level neuropathic pain states, and selectively targeting this pathway may provide effective pain relief for SCI patients.     

重复经颅磁刺激联合针刺治疗脊髓损伤后神经病理性疼痛的临床研究

目的：观察重复经颅磁刺激（rTMS）联合针刺治疗脊髓损伤（SCI）后神经病理性疼痛（NP）的临床疗效。方法：按随机数字表法将99例SCI后NP患者分成对照组、针刺组和联合组,各33例。对照组进行常规基础治疗,针刺组在对照组基础上进行针刺治疗,联合组在针刺组基础上进行rTMS治疗。分别于治疗前及治疗6周后对3组患者进行视觉模拟量表（VAS）、汉密顿抑郁量表（HAMD）、汉密顿焦虑量表(HAMA)及生活质量SF-36量表评估。结果：治疗6周后,3组患者VAS、HAMD和HAMA评分较治疗前均明显降低（P＜0.05）,SF-36量表各项评分较治疗前均明显升高（P＜0.05）;针刺组VAS、HAMD和HAMA评分较对照组均有降低（P＜0.05）,SF-36量表各项评分较对照组均有升高（P＜0.05）;联合组VAS、HAMD和HAMA评分较针刺组和对照组均有降低（P＜0.05）,SF-36量表各项评分较针刺组和对照组均有升高（P＜0.05）。结论：rTMS联合针刺治疗SCI后NP患者,有助于改善患者临床疼痛现象,且在改善患者情绪和生活质量方面疗效显著。     

Combined approaches for the relief of spinal cord injury-induced neuropathic pain

The adequate treatment of spinal cord injury (SCI)-induced neuropathic pain still remains an unresolved problem. The current medications predominantly used in the SCI-induced neuropathic pain therapy are morphine, anticonvulsants, antidepressants, and antiepileptics, which suggests that psychiatric aspects might be important factors in the treatment of neuropathic pain.It is well documented that the modulation of the sensory events is not a unique way for achieving pain relief. In addition, pain patients still express dissatisfaction and complain of unwanted effects of the medications, suggesting that alternative approaches for the treatment of neuropathic pain are essential. In psychiatry, pain relief represents relaxation and a feeling of comfort and satisfaction, which suggests that cognitive and emotional motivations are important factors in the treatment of neuropathic pain. The comorbidity of chronic pain and psychiatric disorders, which is well recognized, suggests that the effective therapeutic relief for neuropathic pain induced by SCI can be achieved in conjunction with the management of the sensory and psychiatric aspects of patient.In this review, we address the feasibility of a combined acupuncture and pharmacotherapy treatment for the relief of neuropathic pain behavior following SCI.     

Low frequencies, but not high frequencies of bi-polar spinal cord stimulation reduce cutaneous and muscle hyperalgesia induced by nerve injury

Spinal cord stimulation (SCS) is an established treatment for neuropathic pain. However, SCS is not effective for all the patients and the mechanisms underlying the reduction in pain by SCS are not clearly understood. To elucidate the mechanisms of pain relief by SCS, we utilized the spared nerve injury model. Sprague–Dawley rats were anesthetized, the tibial and common peroneal nerves were tightly ligated, and an epidural SCS lead implanted in the upper lumbar spinal cord. SCS was delivered daily at one of 4 different frequencies (4 Hz, 60 Hz, 100 Hz, and 250 Hz) at approximately 85% of motor threshold 2 weeks after nerve injury for 4 days. Mechanical withdrawal threshold of the paw and compression withdrawal threshold of the hamstring muscles were measured before and after SCS on each day. All rats showed a decrease in withdrawal threshold of the paw and the muscle 2 weeks after nerve injury. Treatment with either 4 Hz or 60 Hz SCS significantly reversed the decreased withdrawal threshold of the paw and muscle. The effect was cumulative with a greater reversal by the fourth treatment when compared to the first treatment. Treatment with 100 Hz, 250 Hz or sham SCS had no significant effect on the decreased withdrawal threshold of the paw or muscle that normally occurs after nerve injury. In conclusion, SCS at 4 Hz and 60 Hz was more effective in reducing hyperalgesia than higher frequencies of SCS (100 Hz and 250 Hz); and repeated treatments result in a cumulative reduction in hyperalgesia.