Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells（OECs） remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.

The Efficacy and Safety of Continuous Popliteal Sciatic Nerve Block for the Relief of Pain Associated with Critical Limb Ischemia: A Retrospective Study

Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have been administering continuous sciatic nerve block (CSNB) for patients with CLI whose pain could not be relieved by other analgesic tools. The aim of this retrospective study was to investigate the efficacy and safety of CSNB for patients with CLI. Method: We retrospectively investigated 99 patients who received CSNB for the relief of severe pain in the lower limb associated with CLI. Patient demographics, neurological history, complications, and subjective evaluation of the effectiveness of CSNB were investigated from their clinical records. The distal tips of 108 catheters were cultured. Result: One hundred and seventy-two catheters were placed in 99 patients. More than 90% of the patients enjoyed considerable relief of severe pain. The analgesic effect of CSNB was greater in patients with older age and hemodialysis. Thirty-one catheters had positive bacterial colonization. However, no severe infectious complication was found. There was no relationship between the co-existence of diabetes and positive bacterial colonization. We encountered a patient with ASO and diabetes who suffered from persistent motor weakness and hypesthesia even after 3 months of CSNB placement. Conclusions: CSNB provided good pain control for patients with severe pain caused by CLI. Although catheters were frequently found to be colonized, infection at the catheter site was self-limiting even in patients with diabetes.

瑞芬太尼调节IL-10/β-内啡肽信号通路对坐骨神经损伤大鼠疼痛的影响

目的探讨瑞芬太尼对坐骨神经损伤(SNI)大鼠疼痛的影响及作用机制。方法建立SNI大鼠模型,大鼠分为假手术组、模型组、瑞芬太尼低剂量组(5μg·kg^(-1)·min^(-1))、瑞芬太尼高剂量组(20μg·kg^(-1)·min^(-1))和瑞芬太尼+抑制剂组(20μg·kg^(-1)·min^(-1)的瑞芬太尼+10μL IL-10抗体),评估大鼠疼痛阈值,统计坐骨神经指数(SFI),Masson染液评价靶肌肉萎缩情况,酶联免疫吸附法(ELISA)检测白介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α的含量,免疫荧光检测微管相关蛋白(MAP2)的表达,Western blot检测IL-10、β-内啡肽蛋白表达。结果与假手术组比较,模型组大鼠疼痛阈值、SFI和IL-10、β-内啡肽蛋白的表达水平下降,肌肉萎缩、IL-1β、IL-6、TNF-α、MAP2表达增加(P<0.05);与模型组比较,瑞芬太尼低、高剂量组大鼠疼痛阈值、SFI和IL-10、β-内啡肽蛋白的表达水平升高,肌肉萎缩、IL-1β、IL-6、TNF-α、MAP2表达降低,且呈剂量依赖性(P<0.05);与瑞芬太尼高剂量组比较,瑞芬太尼+抑制剂组大鼠疼痛阈值、SFI和IL-10、β-内啡肽蛋白的表达水平下降,肌肉萎缩、IL-1β、IL-6、TNF-α、MAP2表达增加(P<0.05)。结论瑞芬太尼可能通过激活IL-10/β-内啡肽信号通路抑制SNI大鼠的疼痛行为。

齐刺环跳穴干预坐骨神经损伤大鼠脊髓背角炎症因子及胶质原纤维酸性蛋白表达影响的实验研究

目的通过观察齐刺环跳穴对坐骨神经损伤(Sciatic nerve injury,SNI)大鼠脊髓背角炎症因子及胶质原纤维酸性蛋白(Glial fibrillary acidic arotein,GFAP)表达的影响,探讨齐刺环跳穴治疗神经病理痛(Neuropathic pain,NP)的镇痛机制。方法60只SD大鼠随机分为假手术组、模型组、齐刺组、单刺组及药物组,每组12只,采用钳夹法制备大鼠坐骨神经损伤模型。造模第2天开始进行针刺及药物干预,连续14 d。观察各组大鼠干预前后热缩足反射潜伏期(Paw with⁃drawal latency,PWL)的变化,治疗结束后取损伤处坐骨神经,苏木素伊红(HE)染色观察神经形态;取腰3~5脊髓节段ELISA法检测白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor necrosis factor-alpha,TNF-α)蛋白表达水平,实时定量PCR法及免疫组化法检测GFAP表达水平。结果治疗前,与假手术组比较,各组PWL指数降低(P<0.01),与模型组比较,齐刺组治疗后显著改善(P<0.01)。HE染色,模型组神经纤维排列紊乱,齐刺组、单刺组及药物组神经纤维在数量及排列紊乱程度等方面均有改善,齐刺组改善最为明显。ELISA法、RT-PCR法及免疫组化检测,模型组、齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达较假手术组显著升高(P<0.01);与模型组相比,齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达显著下降,齐刺组表达低于单刺组及药物组(P<0.01)。结论齐刺环跳穴缓解坐骨神经痛的镇痛机制可能与下调脊髓背角炎症因子表达,抑制星形胶质细胞活化,降低中枢痛觉敏化程度有关。

麦粒灸对坐骨神经损伤大鼠脊髓组织TLR4/MyD88/NF-κB信号通路表达的影响

目的观察麦粒灸“环跳”对坐骨神经损伤(SNI)大鼠坐骨神经功能、坐骨神经干病理形态及脊髓组织TLR4/MyD88/NF-κB表达的影响,探究麦粒灸治疗SNI的可能机制。方法24只雄性SD大鼠随机分为空白组、假手术组、模型组和麦粒灸组,每组6只。模型组、麦粒灸组采用坐骨神经钳夹制备SNI大鼠模型,造模后第7日起麦粒灸组取患侧“环跳”麦粒灸干预,每次6壮,1次/d,连续10 d。观察造模后第7日及干预结束后大鼠坐骨神经功能指数(SFI)、纤维丝测痛仪测量大鼠机械痛阈值(MWT),ELISA检测脊髓组织一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)含量,HE染色观察坐骨神经干形态,Western blot检测脊髓组织Toll样受体4(TLR4)、核因子(NF)-κBp65、p-NF-κBp65、髓样分化因子88(MyD88)、NF-κB抑制蛋白α(IκBα)、p-IκBα蛋白表达。结果与假手术组比较,模型组大鼠SFI、MWT显著降低(P<0.01),坐骨神经干神经纤维排列紊乱,施万细胞数量明显增多,有大量空泡变性,脊髓组织NO、iNOS含量及TLR4、p-NF-κBp65、MyD88、p-IκBα蛋白表达显著升高(P<0.01);与模型组比较,麦粒灸组大鼠SFI、MWT显著升高(P<0.01),坐骨神经干损伤减轻,细胞排列较整齐,施万细胞数量减少,轴突脱髓鞘及细胞空泡变性减少,脊髓组织NO、iNOS含量及TLR4、p-NF-κBp65、MyD88、p-IκBα蛋白表达显著降低(P<0.05)。结论麦粒灸“环跳”可下调SNI大鼠脊髓组织TLR4、p-NF-κBp65、MyD88、p-IκBα蛋白表达,抑制NO、iNOS分泌,从而缓解疼痛、减轻受损神经组织炎症反应。

三法三穴推拿对坐骨神经损伤大鼠的即刻镇痛作用及其机制

目的观察三法三穴推拿对坐骨神经损伤大鼠的即刻镇痛作用并探讨其机制。方法SD大鼠随机分为假手术组、模型组及推拿组,每组6只。模型组及推拿组建立轻型坐骨神经慢性压迫性损伤模型模拟临床神经病理性疼痛,假手术组仅暴露神经并缝合。推拿组在造模后7 d采用按摩推拿手法模拟仪进行三法三穴推拿干预,假手术组及模型组进行等时间的抓握束缚。分别于造模前(T_(1))、造模后推拿前(T_(2))、推拿后(T_(3))采用机械缩足反射阈值及热缩足反射潜伏期评价三法三穴推拿即刻镇痛效果;评价结束后取大鼠腰膨大节段脊髓背角组织,采用Western blotting法检测各组大鼠脊髓背角组织嘌呤能受体P2Y12(P2RY12)、磷酸化p38丝裂原活化蛋白激酶(p-p38 MAPK)及肿瘤坏死因子α(TNF-α)蛋白。结果与假手术组同时点比较,模型组、推拿组在T_(2)及T_(3)时点MWT、TWL均降低(P均<0.05);与模型组同时点比较,推拿组T_(3)时点MWT、TWL均升高(P均<0.05)。模型组脊髓背角组织P2RY12、p-p38 MAPK、TNF-α蛋白表达均高于假手术组、推拿组(P均<0.05),假手术组及推拿组P2RY12、p-p38 MAPK、TNF-α蛋白表达比较差异无统计学意义(P均>0.05)。结论三法三穴推拿在坐骨神经损伤大鼠中具有较好的即刻镇痛效果,其机制可能为抑制小胶质细胞P2RY12/p38 MAPK/TNF-α通路从而缓解神经病理性疼痛。

不同时间股神经-坐骨神经阻滞对胫腓骨骨折患者术后疼痛与谵妄的影响比较

目的:比较不同时间股神经-坐骨神经阻滞对胫腓骨骨折患者术后疼痛与谵妄的影响。方法:采取回顾性分析法,将2022年7月—2023年6月福州市第二医院麻醉科收治的100例胫腓骨骨折患者根据股神经-坐骨神经阻滞时间不同分成A组与B组,A组50例于气管插管后手术切皮前(术前)行股神经-坐骨神经阻滞,B组50例于手术缝合结束即刻(术后)行股神经-坐骨神经阻滞,两组其余麻醉方法相同。观察两组麻醉效果、术后疼痛程度、认知功能、术后谵妄及不良反应发生率。结果:A组神经阻滞镇痛持续时间长于B组,差异有统计学意义(P<0.05),A组术后苏醒时间早于B组,丙泊酚用量、瑞芬太尼用量均少于B组,差异均有统计学意义(P<0.05);A组术后2、6、12、24 h视觉模拟评分法(VAS)评分均低于B组,差异均有统计学意义(P<0.05);两组术后1、3 d的简易智力状态检查量表(MMSE)评分均低于术前,A组术后1、3 d的MMSE评分均高于B组,差异均有统计学意义(P<0.05);A组术后谵妄发生率低于B组,差异有统计学意义(P<0.05);A组不良反应发生率低于B组,差异有统计学意义(P<0.05)。结论:术前股神经-坐骨神经阻滞在胫腓骨骨折患者手术中的应用效果较好,与术后股神经-坐骨神经阻滞相比,能够延长神经阻滞镇痛持续时间,缩短术后苏醒时间,减少麻醉维持用药量,减轻术后疼痛及认知功能损伤,降低术后谵妄及不良反应发生率。

收肌管阻滞与单次坐骨神经阻滞联合药物镇痛对全膝关节置换后疼痛的影响

背景:全膝关节置换术是治疗晚期骨关节炎的有效手段,但术后疼痛和关节功能恢复是主要的挑战。神经阻滞和混合药物注射是两种常用的镇痛方法,但其联合应用的效果尚不明确。目的:探讨在全膝关节置换过程中应用超声引导下连续性收肌管阻滞+单次坐骨神经阻滞+“鸡尾酒”混合药物镇痛对患者置换后疼痛缓解以及关节功能恢复的影响。方法:纳入于2022年1-5月河北省沧州中西医结合医院收治的骨关节炎患者120例,随机分为2组(n=60),观察组采用超声引导下连续性收肌管阻滞+单次坐骨神经阻滞+“鸡尾酒”混合药物镇痛,对照组采用超声引导下连续性收肌管阻滞+单次坐骨神经阻滞。比较两组患者在目测类比评分、特种外科医院关节功能评分、疼痛递质、炎症因子表达水平、不良反应发生以及术后徒手肌力方面的差异。结果与结论:①观察组患者在术后6,8,12,24,48,72 h时的静息、运动状态下目测类比评分均低于对照组(P<0.05);②观察组患者在术后1,3个月时的特种外科医院评分显著高于对照组(P<0.05);③在疼痛递质以及炎症因子方面,观察组患者的表达水平要显著低于对照组(P<0.05);④在不良反应以及术后徒手肌力方面,两组之间差异无显著性意义(P>0.05);⑤提示在全膝关节置换过程中应用超声引导连续性收肌管阻滞和单次坐骨神经阻滞的同时,采用“鸡尾酒”混合镇痛药物关节腔注射的方式可以起到很好的镇痛效果,更利于关节功能的恢复,也能缓解术后疼痛以及炎症,同时还具有较高的安全性。

超声引导腹股沟上髂筋膜阻滞在膝关节镜手术中的应用

目的:比较膝关节镜手术中腹股沟上髂筋膜阻滞及股神经联合坐骨神经阻滞的临床效果。方法:选择行膝关节镜手术治疗的患者共44例,随机分为两组,分别采用腹股沟上髂筋膜阻滞(A组)和股神经联合坐骨神经阻滞(B组)。比较两组患者感觉和运动阻滞起效时间及两种神经阻滞穿刺过程中的患者满意度,术后镇痛泵有效按压次数、补充镇痛药物的用量,进入手术室(T0)、术后2 h(T_(1))、术后6 h(T_(2))、术后12 h(T_(3))和术后24 h(T_(4))的静息视觉模拟评分法(visual analogue scale,VAS)和5 m步行试验的VAS评分,术后T_(2)、T_(3)和T_(4)的患侧股四头肌肌力及术后恶心呕吐、头晕等不良事件的发生情况。结果:A组的感觉神经阻滞起效时间比B组明显缩短,A组患者神经阻滞穿刺过程中的满意度比B组明显提高(P<0.05);A组患者术后6 h和术后12 h的静息VAS评分比B组显著降低、股四头肌肌力评分明显优于B组,A组术后12 h、术后24 h的5 m步行实验的VAS评分较B组显著降低(P<0.05);A组患者的术后镇痛泵按压次数和补救镇痛药物用量均少于B组,且首次下床活动时间早于B组(P<0.05)。结论:相较于股神经联合坐骨神经阻滞复合全身麻醉,超声引导腹股沟上髂筋膜阻滞复合全身麻醉对行膝关节镜手术治疗的患者镇痛效果更佳,能迅速阻滞感觉神经,降低VAS评分,减少止痛泵的加药次数和镇痛药物的补救量,对下肢肌力的影响较小,促进患者的早期康复。

Effects of continuous peripheral nerve block by tetrodotoxin on growth associated protein-43 expression during neuropathic pain development

BACKGROUND： Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 （GAP-43） in the spinal cord and dorsal root ganglion, local anesthetics blocking electrical impulse propagation of nerve fibers may also affect the expression of GAP-43 in the spinal cord and dorsal root ganglion. OBJECTIVE： To determine the effects of continuous peripheral nerve block by tetrodotoxin before and after nerve injury on GAP-43 expression in the dorsal root ganglion during the development of neuropathic pain. DESIGN： A randomized controlled animal experiment. SETTINGS： Department of Anesthesiology, the Second Hospital of Xiamen City; Department of Anesthesiology, the Second Affiliated Hospital of Shantou University Medical College. MATERIALS： Thirty-five Spragne Dawley （SD） rats, weighing 200 - 250 g, were randomly divided into four groups： control group （n =5）, simple sciatic nerve transection group （n =10）, peripheral nerve block before and after sciatic nerve transection groups （n =10）. All the sciatic nerve transection groups were divided into two subgroups according to the different postoperative survival periods： 3 and 7 days （n =5） respectively. Mouse anti-GAP-43 monoclonal antibody （Sigma Co., Ltd.）, supervision TM anti-mouse reagent （HRP, Changdao antibody diagnosis reagent Co., Ltd., Shanghai）, and HMIAS-100 image analysis system （Qianping Image Engineering Company, Tongji Medical University） were employed in this study. METHODS： This experiment was carried out in the Department of Surgery and Pathological Laboratory, the Second Affiliated Hospital of Shantou University Medical College from April 2005 to April 2006. ①The animals were anesthetized and the right sciatic nerve was exposed and transected at 1 cm distal to sciatic notch. ② Tetrodotoxin 10 μg/kg was injected percutaneously between the greater trochanter and the posterior superior iliac spine of fight hind limb to block the sciatic nerve proximally at 1 hour before or 4 hours after nerve injury respectively, the injection was repeated in all the rats every 12 hours.③ At 3 or 7 days after nerve injury, immunohistochemistry and image analysis were used to evaluate the expression of GAP-43 in the dorsal root ganglions of L5 to the transected sciatic nerve, and quantitative analysis was also performed. ④ Statistical analysis was performed using one way analysis of variance followed by t test. MAIN OUTCOME MEASURE： Expression of GAP-43 in the fight dorsal root ganglions of L5. RESULTS： All the 35 SD rats were involved in the final analysis of results. In normal rats, there were very low expressions of GAP-43 in the dorsal root ganglions. In simple sciatic nerve transection rats 3 and 7 days after sciatic nerve transection, the average absorbance value of GAP-43 immunopositive neurons were significantly different from that in normal rats （t =8.806, 6.771, P 〈 0.01）. Whereas 3 and 7 days after sciatic nerve transection in rats with peripheral nerve block before and after nerve injury, the average absorbance value of GAP-43 immunopositive neurons were not significantly different from that in normal rats （P 〉 0.05）. CONCLUSION： Local anesthetic continuous peripheral nerve block before or after nerve injury can suppress nerve injury induced high expression of GAP-43 during the development of neuropathic pain.

Ameliorative effects of standardized extract from Trigonella foenum-graecum L.seeds on painful peripheral neuropathy in rats

Objective:To evaluate the effects of the standardized extract of fenugreek(Trigonella foenumgraecum L.Family:Leguminasae) seed(IND01) in animal models of peripheral neuropathy. Methods:IND01 was prepared from fenugreek seeds and standardized by high performance liquid chromatography to a marker compound,trigonelline.The effects of daily oral administration of IND01(50,100 and 200 mg/kg) were studied in rats after partial sciatic nerve ligation(PSNL) and sciatic nerve crush injury(SNCI) during 30-days period.The measurements on thermal hyperalgesia(TH),motor function test(MFT) score and motor nerve conduction velocity (MNCV) were recorded.Results:IND01 offered sustained protection against TH and deranged MFT scores in both models from 7-day onwards.Fifteen days of daily oral administration of IND01 restored MNCV reduction in rats with SNCI but not with PSNL.Conclusions:IND01 was found to be effective in rat models of painful peripheral neuropathy.

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats

Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.

Local Peripheral Effects of <i>β</i>-Caryophyllene through CB₂Receptors in Neuropathic Pain in Mice

β-Caryophyllene (BCP) is known as a common constitute of the essential oils of numerous food plants and primary component in Cannabis. In this study, we investigated the effect of local intraplantar (i.pl.) injection of BCP on mechanical hypersensitivity induced by partial sciatic nerve ligation (PSNL) in mice. Relative to sham operation controls, mice with the PSNL displayed a maximum level of hyperresponsiveness to von Frey metallic filament on post-operative day 7. PSNL-induced allodynia was seen in the ipsilateral side of nerve ligation, but not in the contralateral side. The i.pl. injection of BCP into the ipsilateral hindpaw to PSNL attenuated mechanical allodynia in a dose-dependent manner. BCP injection into the contralateral hindpaw did not produce anti-allodynic effects, suggesting a local peripheral anti-allodynic effect of BCP. Anti-allodynic effects induced by i.pl. injection of BCP were prevented by pretreatment with the cannabinoid (CB2) receptor antagonist AM630, but not by the CB1 receptor antagonist AM251. These data suggest that i.pl. injection of BCP could produce anti-allodynia by activating peripheral CB2 receptors, but not CB1 receptors in a mouse model of neuropathic pain. Taken together, these results suggest that peripheral CB2 receptors may contribute to the effectiveness of BCP in the treatment of neuropathic pain disorders.

The Effect of Different Regional Blocks: Combined Femoral-Sciatic, Spinal and Epidural Blocks on the Different Side Effects of Arterial Tourniquet in Patients Undergoing Lower Limb Orthopedic Surgeries —A Randomized Controlled Trail

Background: Pneumatic arterial tourniquet is a very commonly used technique in limb surgeries to provide bloodless field to facilitate dissection and decrease blood loss. However, arterial tourniquet has many deleterious effects including hemodynamic changes, serum lactate and potassium level changes and tourniquet-induced pain which sometimes can be severe and intolerable. Aim of the study: To evaluate the effect of different regional blocks: femoral-sciatic, spinal and epidural blocks on serum lactate and potassium levels and the degree of arterial tourniquet-induced pain in patients undergoing lower limb orthopedic surgeries. Methods: 60 patients underwent lower limb orthopedic surgery with application of tourniquet for duration not more than 90 minutes. Patients were assigned randomly to one of three groups (20 each) Group I had sciatic-femoral block, Group II: patients had spinal anesthesia and Group III: patients had epidural anesthesia. Intraoperative hemodynamics, changes in serum potassium and lactate levels and tourniquet pain after tourniquet inflation & deflation, were recorded. Results: There was no statistically significant difference among the three groups regarding tourniquet pain after tourniquet inflation (p = 0.872) and deflation (p = 0.902), and regarding serum levels changes of potassium (p = 0.067) and lactate (p = 0.051). However, each group showed statistically significant increase in post deflation tourniquet pain (p = 0.003, 0.002, 0.003, in groups F, S, E respectively) and serum potassium (p = 0.004, 0.006, 0.000, in groups F, S, E respectively) and lactate levels (p = 0.004, 0.000, 0.000, in groups F, S, E respectively) when compared to the pre-deflation values, and the increase was directly proportional to the duration of tourniquet. Conclusion: the three different types of anesthesia (femoral-sciatic, spinal and epidural block) have the same effect on serum lactate and potassium levels and the degree of tourniquet pain, which were related to the duration of tourniquet inflation.

Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats

Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.

The Primary Motor Cortex Stimulation Attenuates Cold Allodynia in a Chronic Peripheral Neuropathic Pain Condition in <i>Rattus norvegicus</i>

Background: The primary motor cortex (M1) stimulation (MCS) is a useful tool for attenuation of the peripheral neuropathic pain in patients with pharmacologically refractory pain. Furthermore, that neurological procedure may also cause antinociception in rodents with neuropathic pain. Cold allodynia is a frequent clinical finding in patients with neuropathic pain, then, we evaluated if an adapted model of neuropathy induced by chronic constriction injury (CCI) of the ischiadicus nervus (sciatic nerve) produces cold allodynia in an animal model of chronic pain. In addition, we also investigated the effect of the electrical stimulation of the M1 on chronic neuropathic pain condition in laboratory animals. Methods: Male Wistar rats were used. An adapted model of peripheral mononeuropathy induced by CCI was carried out by placing a single loose ligature around the right sciatic nerve. The acetone test was used to evaluate the cold allodynia in CCI or Sham (without ligature) rats. The MCS (M1) was performed at low-frequency (20 μA, 100 Hz) during 15 s by deep brain stimulation (DBS-Thomas Recording device) 21 days after CCI or Sham procedures. The cold allodynia was measured before and immediately after the neurostimulation of M1 in the following time-window: 0, 15 and 30 min after MCS. Results: Cold allodynia threshold increased in animals with chronic neuropathic pain submitted to the acetone test 21 days after the CCI surgery. The M1-stimulation by DBS procedure decreased the cold allodynia immediately and until 30 min after M1-stimulation in rats with chronic neuropathic pain. Conclusion: The current proposal for a CCI model by a single loose ligature of the sciatic nerve can be employed as an experimental model of chronic neuropathic pain in rats submitted to peripheral nervous system injury. The M1-stimulation produced antinociception in rats with chronic neuropathic pain. Thus, we reinforced that the MCS decreases cold allodynia in laboratory animals submitted to persistent sciatic nerve constriction and can be a more reasonable procedure for the treatment of chronic intractable neuropathic pain.

Microencapsulated Schwann cell transplantation inhibits P2X3 receptor expression in dorsal root ganglia and neuropathic pain

Schwann cell transplantation is a promising method to promote neural repair, and can be used for peripheral nerve protection and myelination. Microcapsule technology largely mitigates immune rejection of transplanted cells. We previously showed that microencapsulated olfactory ensheathing cells can reduce neuropathic pain and we hypothesized that microencapsulated Schwann cells can also inhibit neuropathic pain. Rat Schwann cells were cultured by subculture and then microencapsulated and were tested using a rat chronic constriction injury（CCI） neuropathic pain model. CCI rats were treated with Schwann cells or microencapsulated Schwann cells and were compared with sham and CCI groups. Mechanical withdrawal threshold and thermal withdrawal latency were assessed preoperatively and at 1, 3, 5, 7, 9, 11 and 14 days postoperatively. The expression of P2X3 receptors in L4-5 dorsal root ganglia of the different groups was detected by double-label immunofluorescence on day 14 after surgery. Compared with the chronic constriction injury group, mechanical withdrawal threshold and thermal withdrawal latency were higher, but the expression of P2X3 receptors was remarkably decreased in rats treated with Schwann cells and microencapsulated Schwann cells, especially in the rats transplanted with microencapsulated Schwann cells. The above data show that microencapsulated Schwann cell transplantation inhibits P2X3 receptor expression in L4-5 dorsal root ganglia and neuropathic pain.

超前股神经-坐骨神经阻滞对胫腓骨骨折手术患者术后短期认知功能及镇痛的影响

目的探讨超前股神经-坐骨神经阻滞对胫腓骨骨折手术患者术后短期认知功能及镇痛的影响。方法纳入西南医科大学附属医院2020年12月~2021年8月择期行胫腓骨切开复位内固定术的患者140例,将患者分为对照组(术后阻滞组,n=70)和观察组(超前阻滞组,n=70),两组均选择全麻复合股神经-坐骨神经阻滞,观察两组不同时间点[术后1 d(T0)、3 d(T1)、5 d(T2)、7 d(T3)及出院当天(T4)]术后短期认知功能[简易智能量表(MMSE)及谵妄量表(CAM)分别及联合评估],比较两组镇痛效果[T0、T1、T2及T3静止和活动时通过视觉模拟评分法(VAS评分)获得疼痛程度、术后补救镇痛率、神经阻滞镇痛持续时间、术中瑞芬太尼泵注总量],术中丙泊酚泵注总量,术后苏醒时间,住院时间,出现并发症几率及继续康复治疗率。结果两量表分别评估不同时间点(T0、T1、T2、T3及T4时)术后认知功能障碍及术后谵妄,两组发生率比较差异无统计学意义(P>0.05),而两量表联合评估术后短期认知功能,与对照组比较,T0时观察组围术期神经认知障碍发生率明显降低(P=0.049),而T1、T2、T3及T4时,两组发生率比较差异无统计学意义(P>0.05);T0时,观察组静止和活动时的疼痛程度均低于对照组(P<0.05),此外,观察组神经阻滞镇痛时间较对照组延长(P=0.001),观察组术中瑞芬太尼泵注总量低于对照组(P=0.002);与对照组相比,观察组术后苏醒时间明显缩短(P<0.0001)。结论在胫腓骨骨折手术中,超前应用股神经-坐骨神经阻滞较术后应用而言,更有利于术后短期认知恢复,同时围术期镇痛效果更佳,可加速患者康复。

不同强度电针足三里对化疗所致周围神经病理性疼痛大鼠行为学及坐骨神经传导速度的影响

目的:观察不同强度电针足三里对化疗所致周围神经病理性疼痛(CIPNP)大鼠行为学及神经传导速度的影响。方法:SD大鼠随机分为空白组、模型组和低、中、高强度电针组。模型组及各电针组大鼠腹腔注射奥沙利铂溶液,建立CIPNP大鼠模型。造模成功后,各电针组取双侧足三里穴进行不同强度电针干预,干预14 d。HE染色观察各组大鼠脊髓组织病理学改变。比较各组大鼠机械痛阈值、坐骨神经传导速度及脊髓组织胶质纤维酸性蛋白(GFAP)表达水平。结果:空白组大鼠脊髓组织神经元细胞大小正常,细胞核位于细胞中央,无明显空腔。模型组大鼠脊髓组织结构紊乱,出现大量的空腔,炎性浸润严重,存在大量炎性细胞,正常神经元大量减少。各电针组大鼠脊髓结构较完整,炎性浸润程度较轻,炎性细胞较少,正常神经元较多。干预后,与模型组比较,低、中、高强度电针组大鼠机械痛阈值升高,坐骨神经传导速度提高,脊髓组织GFAP蛋白表达水平明显降低(均P<0.05)。结论:电针足三里可以通过降低CIPNP大鼠的机械痛阈值、提升坐骨神经传导速度、降低脊髓组织GFAP表达水平以缓解周围神经毒性。