Electroacupuncture (EA), a modern adaptation of traditional acupuncture, has shown promising analgesic effects across various pain models. However, the underlying central mechanisms remain insufficiently characterized. The dorsal horn of the spinal cord serves as a critical hub for the transmission and modulation of nociceptive signals. Increasing evidence suggests that spinal disinhibition, primarily resulting from impaired excitability of inhibitory interneurons and diminished synthesis or release γ-aminobutyric acid (GABA) and glycine, accounts for the development and maintenance of pain. In this study, we investigated whether EA alleviates inflammatory pain by modulating the activity of GABAergic inhibitory interneurons in the superficial dorsal horn of the spinal cord. A murine model of inflammatory pain was established by subcutaneous injection of complete Freund's adjuvant (CFA) into the hind paw. EA was applied at the Huantiao (GB30) and Yanglingquan (GB34) acupoints on alternate days following CFA injection. Mechanical hypersensitivity was assessed by paw withdrawal threshold. Neuronal activity was evaluated using immunofluorescence staining for c-fos, Lmx1b, Pax2, and GABA. Furthermore, whole-cell patch-clamp recordings were conducted on spinal slices from GAD67-GFP transgenic mice to assess the electrophysiological properties of GABAergic interneurons. EA significantly attenuated mechanical hypersensitivity in CFA-treated mice without affecting locomotor function. Immunofluorescence staining revealed that EA enhanced c-fos expression in the dorsal horn during early stages of treatment, reduced the proportion of c-fos-positive excitatory (Lmx1b-positive) neurons, and markedly increased the activation of inhibitory (Pax2-positive and GABA-positive) interneurons. In addition, electrophysiological recordings demonstrated that EA significantly depolarized the resting membrane potential and increased the firing frequency of GAD67-GFP-positive inhibitory interneurons in the CFA + EA group compared to the CFA group. Collectively, our results suggest EA at Huantiao and Yanglingquan acupoints could relieve inflammatory pain, potentially through enhancing of the excitability and activity of GABAergic inhibitory interneurons in the spinal dorsal horn. This study provides novel mechanistic insight into spinal modulation of nociceptive processing by EA and supports its therapeutic promise for inflammatory pain management.

The intracellular calcium buffer system plays a critical role in shaping the spatiotemporal profile of calcium signaling. In contrast to calcium influx and clearance from the cytosol, our understanding of the calcium buffer system and its role in neuropsychiatric disorders is limited. Shank3 deficiency is a key risk factor for autism and other psychiatric disorders, and many important downstream mechanisms, relating to signaling pathways, cellular physiology and morphology, and neuronal circuitry, have been uncovered. Here we report prominent alterations in the calcium signaling profile of Shank3-/- dopaminergic (DA) neurons in the ventral tegmental area (VTA). Calcium transients from Shank3-/- DA neurons exhibit enhanced amplitudes and faster decay rates. Subsequent proteomic analysis of VTA brain tissue revealed that parvalbumin (PV) expression was significantly downregulated, which was subsequently confirmed by immunostaining results. As PV is an important component of the endogenous calcium buffer system, we employed the added-buffer approach together with 2-photon and ratiometric calcium and demonstrated a reduction in the endogenous calcium buffer capacity (KE) in Shank3-/- neurons. Therefore, the downregulation of PV protein and the associated decrease in calcium buffer capacity are key pathogenic factors resulting from Shank3 deficiency.

Background: Postherpetic neuralgia (PHN) causes chronic pain and emotional dysfunction, but its underlying mechanisms are unknown. Methods: We first compared the structural and functional magnetic resonance imaging (MRI) of PHN-anxiety patients with healthy controls (HCs). Then, we created a PHN comorbid anxiety-like model by injecting resiniferatoxin (RTX) intraperitoneally and used Fos-CreER::Ai9 mice to validate brain regions with volume differences in MRI. Furthermore, we combined behavioral experiments with electrophysiology, viral tracing, in vivo fiber-photometry, optogenetics, and chemogenetics, to analyze the role of the basolateral amygdala (BLA)-anterior cingulate cortex (ACC) circuit in PHN comorbid anxiety-like mice multi-dimensionally. Results: According to neuroimages, patients with PHN-anxiety comorbidity have decreased amygdala volume and decreased functional connection (FC) of the BLA and ACC. Furthermore, we created a PHN comorbid anxiety-like model by injection of RTX intraperitoneally, and these mice showed dysesthesia and anxiety-like behaviors 3 weeks after RTX injection. Then, we discovered that BLA and ACC were related to PHN comorbid anxiety-like behaviors using Fos-CreER::Ai9 mice. Immunohistochemistry and electrophysiology revealed enhanced activation of BLA glutamatergic (BLAGlu) neurons in PHN comorbid anxiety-like mice. Opto/chemogenetic activating BLAGlu neurons aggravated pain threshold in PHN comorbid anxiety-like mice. Inhibiting BLAGlu alleviates mechanical nociception, thermal hyperalgesia, and anxiety-like behavior. Moreover, the elevated excitability of BLAGlu neurons resulted in increased excitatory inputs to the ACC. Selective activation or inhibition of the BLAGlu-ACC pathway exacerbated or alleviated the pain and anxiety behavior, respectively. Conclusion: Findings in this study will provide new insight for understanding the central pathomechanism underlying PHN-anxiety comorbidity, as well as serve as solid theoretical underpinnings for the management of PHN.

BACKGROUND:This randomized controlled clinical trial aims to assess the clinical effect of splanchnic nerve block through transdiscal and paraspinal approaches in treating pain from advanced pancreatic cancer. METHODS:Patients with progressive pancreatic cancer pain who were treated in the Pain Department of the First Affiliated Hospital of Nanchang University from December 2021 to March 2023 were selected. According to the inclusion and exclusion criteria, 34 patients were randomly divided into a transdiscal group (n = 17) and a paraspinal group (n = 17). The patient's intraoperative puncture time and the number of digital subtraction angiography fluoroscopy exposures were recorded. The Visual Analogue Scale (VAS), patient satisfaction scale, Karnofsky score, morphine consumption, and occurrence of adverse events were recorded preoperatively and 1 day, 3 days, 1 week, 1 month, and 3 months after surgery. RESULTS:A total of 14 patients were followed up in the transdiscal group, and 15 patients were followed up in the paraspinal group. There was no significant difference in the general condition between the 2 groups before the operation. The puncture time and number of fluoroscopies in the transdiscal group were significantly less than in the paraspinal group (P < .001). There was no significant difference in VAS, patient satisfaction scale, or Karnofsky score between the 2 groups at each postoperative time point. In the same group, the VAS scores at each time point after operation were significantly lower than those before operation (P < .001). The 2 groups had no significant difference in the total incidence of complications. CONCLUSION:Splanchnic nerve block paraspinal had a significant effect on the treatment of advanced pain in pancreatic cancer patients. However, transdiscal is equally effective, the positioning is more accurate, the operation is simpler, and it is a better choice.

Purpose:Prior studies have suggested that immune cells play a crucial role in Low Back Pain (LBP). We employed a bi-directional Mendelian randomization (MR) study to investigate the causal relationship of immune cells with the risk of LBP. Patients and Methods:Single Nucleotide Polymorphisms (SNPs) that had a significant genetic association with immune cells were used as instrumental variables (IVs). The inverse variance weighted (IVW) method was used as the primary approach for MR analyses. To assess the robustness, sensitivity analyses were further performed using MR-Egger and MR-PRESSO. Results:The MR analysis revealed a causal relationship between six types of immune cells and LBP (P < 0.05), including CD4 Treg AC (OR, 0.925; 95% CI, 0.878-0.974; P = 0.003), CD19 on CD20- CD38- (OR, 0.938; 95% CI, 0.898-0.979; P = 0.003), CD4 on HLA DR+ CD4+ (OR, 0.947; 95% CI, 0.909-0.987; P = 0.010), CD25 on CD39+ CD4+ (OR, 0.954; 95% CI = 0.922-0.988; P = 0.008), CD14 on CD33br HLA DR+ CD14dim (OR, 0.950; 95% CI = 0.916-0.985; P = 0.006), and CD4RA on TD CD4+ (OR, 1.030; 95% CI, 1.012-1.048; P = 0.001). Reverse MR analysis found no evidence of potential causal effects of genetically predicted LBP on the six types of immune cells. Conclusion:This study has demonstrated a close genetic connection between immune cells and LBP, providing valuable insights for future clinical research.

Postherpetic neuralgia (PHN) is a chronic pain condition that develops in the area of a previous herpes zoster (shingles) infection. Protein tyrosine phosphatase receptor type K (PTPRK) encodes a receptor-type protein tyrosine phosphatase involved in regulating cell signaling, growth, and neural development. p38 MAPK signaling pathway regulates cellular responses to stress, inflammation, and cytokines, influencing processes like cell differentiation, apoptosis, and immune response. This study aimed to discover the role of PTPRK in PHN and the underlying mechanism. Bioinformatics analysis was used to screen for differentially expressed genes and enrichment pathways of these genes in PHN and control groups. Resiniferatoxin (RTX) was used to induce rat PHN model. Mechanical allodynia and thermal hypoalgesia were assessed by measuring the paw withdrawal threshold and latency. The levels of inflammatory cytokines were detected by ELISA and RT-qPCR. Western blot was performed to analyze the protein levels of DUSP1/p38 MAPK signaling pathway. Results showed that PTPRK expression was increased in RTX-induced rat PHN model. Besides, PTPRK promoted mechanical allodynia, thermal hypoalgesia, and inflammation in RTX-induced rat PHN model via activating DUSP1/p38 MAPK signaling pathway in rat dorsal root ganglia (DRG) tissues. In addition, PTPRK overexpression promoted inflammation by activating DUSP1/p38 MAPK signaling pathway in rat DRG cells. In conclusion, PTPRK promoted RTX-induced PHN via activating DUSP1/p38 MAPK signaling pathway in DRG, which might provide a reference for the treatment of PHN.

BackgroundSciatica (neuropathic pain [NP]) is a common disease characterized by pain from radiation along the sciatic nerve. The aim of this study was to study the genes associated with chronic systolic injury of sciatic nerve (SCN-CCI) in rats by RNA-Seq technique, and to explore their potential as therapeutic targets.MethodsSciatic nerve rat model was obtained by ligation of sciatic nerve and divided into two groups: SCN-CCI group and Sham group. Behavioral assessments were performed to evaluate pain sensitivity, following which their spinal cord dorsal horn were resected and RNA sequencing was conducted to identify differentially expressed genes (DEGs). Bioinformatics and functional enrichment analysis was performed to identify promising DEGs and their related biological processes and pathways associated with SCN-CCI. PPI network analysis and hub gene identification were conducted. QRT-PCR, western blot, ELISA, and immunofluorescence staining were performed on rat models to validate the expression of these hub genes and investigate related proteins and inflammatory markers.ResultsThe SCN-CCI rat model was successfully obtained, exhibiting increased pain sensitivity compared to the Sham group, as indicated by decreased mechanical allodynia thresholds, thermal latencies, and increased paw withdrawals. RNA-Seq analysis identified 117 DEGs in the SCN-CCI rat model, involved in various biological processes and pathways related to sciatica. PPI network analysis revealed hub genes, including Ly6g6e, which exhibited significant differential expression. QRT-PCR and Western blot analysis confirmed the expression patterns of these hub genes. Pain behavior assessment demonstrated reduced pain thresholds and increased paw flinching responses in the SCN-CCI group. Furthermore, the SCN-CCI group showed upregulated expression of Ly6g6e, increased protein levels of Ly6g6e, CGRP, and NGF, as well as elevated levels of IL-1β, MCP-1, and IL-6, and microglial cell activation in the spinal dorsal horn. ELISA results confirmed the increased levels of IL-1β, MCP-1, and IL-6 in the spinal dorsal horn.ConclusionThese comprehensive findings provide valuable insights into the SCN-CCI rat model, DEGs associated with sciatica, hub genes (Ly6g6e as promising targets), pain behavior changes and molecular alterations.

AIMS:Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain. METHODS:After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms. RESULTS:Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors. CONCLUSION:Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms.

Previous observational studies focused on the association of tea intake and allergic diseases. However, it is not known whether these associations are causal. We used a bidirectional Mendelian randomization (MR) study to assess the causal relationship of tea intake with the risk of allergic diseases, such as atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). Single-nucleotide polymorphisms (SNPs) which had genetic statistical significance with tea intake were used as instrumental variables (IVs). We employed heritable IVs of tea intake from the UK Biobank, which included 447,485 samples. Sensitivity analyses were further performed using MR Egger and MR-PRESSO. Inverse variance weighted (IVW) method was used as the main approach. In this MR study, 40 independent SNPs were selected for tea intake. The MR analysis revealed that an increase in genetically predicted tea intake was associated with a lower risk of AD (OR = 0.709, 95% CI = 0.546-0.919, p = 0.009). Furthermore, we observed a causal effect of genetically predicted tea intake on the risk of AA (OR = 0.498, 95% CI = 0.320-0.776, p = 0.002). However, no significant causal relationship was found between genetically predicted tea intake and AR (OR = 1.008, 95% CI = 0.998-1.017, p = 0.115). Our MR analysis suggested that increased tea intake may reduce the risk of AD and AA in European population. This suggests that tea intake is likely a trigger or a prevention strategy for AD and AA.

目的:分析三叉神经痛(trigeminal neuralgia,TN)病人疼痛灾难化的危险因素并建立风险预测模型,为临床有效预防TN病人疼痛灾难化的发生提供参考依据.方法:选取2021年1月至2023年3月在南昌大学第一附属医院疼痛科住院的205例TN病人为研究对象,根据是否发生疼痛灾难化分为疼痛灾难化组和无疼痛灾难化组,采用单因素分析和多因素Logistic回析探讨疼痛灾难化的危险因素,通过R软件构建列线图风险预测模型并验证效果.结果:Logistic回归表明年龄、文化程度、疼痛程度、焦虑、抑郁、睡眠质量是TN病人疼痛灾难化的危险因素,Bootstrap法内部验证显示平均ROC曲线下面积(area under the curve,AUC)为0.978、C-Index为0.978,外部验证显示AUC为0.882、模型特异度为0.941、灵敏度为0.792,表明模型区分度较好,Calibrate曲线图显示模型校准度良好,DCA结果显示模型临床获益水平较高.结论:年龄、文化程度、疼痛程度、焦虑、抑郁、睡眠质量是TN病人疼痛灾难化的危险因素,该列线图风险预测模型具有良好的预测效能和临床应用价值.

BACKGROUND:Previous observational studies focused on the association of coffee consumption and neurological disease. However, it is not known whether these associations are causal. METHODS:We used Mendelian randomization (MR) study to assess the causal relationship of coffee intake with the risk of neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, and migraine. Single-nucleotide polymorphisms (SNPs) which had genetic statistical significance with coffee intake were used as instrumental variable (IV). Genetic instruments were stretched from the MRC-IEU (MRC Integrative Epidemiology Unit) analysis on the UK Biobank. We performed MR analyses using the inverse variance weighted (IVW) method as the main approach. Sensitivity analyses were further performed using MR-Egger and MR-PRESSO to assess the robustness. RESULTS:In the MR analysis, 40 SNPs were selected as IV, the F statistics for all SNPs ranged from 16 to 359. In IVW approach, our results provide genetic evidence supporting a potential causal association between coffee intake and a lower risk of migraine (OR = 0.528, 95% CI = 0.342-0.817, P = 0.004) and migraine with aura (OR = 0.374, 95% CI = 0.208-0.672, P = 0.001). However, we found no significant association between coffee intake and other neurological diseases along with their subtypes in this MR study. CONCLUSION:Using genetic data, our MR study found significant evidence supporting a causal association between coffee intake and migraine. This suggests that coffee consumption is likely a trigger or a prevention strategy for migraine.

Purpose To investigate the clinical efficacy of transforaminal endoscopic discectomy (TED) in treating recurrent lumbar disc herniation. Methods Clinical datal of 31 patients who were hospitalized in the Department of Pain Management, First Affiliated Hospital of Nanchang University, between 2015 and 2018 due to recurrent lumbar disc herniation were collected and analyzed retrospectively. Visual analogue scale (VAS) scores and Japanese Orthopedic Association (JOA) scores were used to assess alterations of patients’ leg pain intensity and nerve function, respectively. The Modified MacNab criteria were used to evaluate patients’ excellent and good rates. Results Compared to clinical data before surgery, there was a significant reduction in VAS scores ( P < 0.01) along with a significant improvement in JOA scores ( P < 0.01) at 2 years after revision surgery. The patients’ excellent and good rates were 83.9% at the 2 years after surgery. Conclusion The TED is safe and effective in the long term and is applicable to the treatment of recurrent lumbar disc herniation.

目的 比较放射式体外冲击波与超声引导下神经阻滞治疗足底筋膜炎的临床疗效.方法 40 例门诊足底筋膜炎患者按治疗方式分为放射式体外冲击波治疗组(S组)和超声引导下神经阻滞治疗组(U组)各 20 例.两组分别在治疗前及治疗第 1、2、4、8 周,采用视觉模拟评分法(VAS)判断疼痛程度.采用足功能指数量表(FFI)评估治疗前及治疗第 1、2、4、8 周足部疼痛及功能变化,观察两组治疗过程中出现的不良反应.结果 与治疗前比较,两组治疗后第 1、2、4、8 周VAS评分均有显著下降(P均<0.05),且U组治疗第 1、2、4 周VAS评分较S组下降明显(P<0.05);U组治疗第1、2、4、8 周后FFI总分、活动受限评分较S组显著下降(P均<0.05),治疗第 2、4 周后FFI疼痛评分较S组下降明显(P<0.05),治疗第 4、8 周后FFI残疾评分较S组下降显著(P<0.05);两组未出现出血、感染、过敏等严重不良反应.结论 两种治疗方式均可有效治疗足底筋膜炎,且在治疗 8周内超声引导下神经阻滞疗效优于放射式体外冲击波治疗.

The present study was aimed to investigate the clinical significance of methyl-CpG binding protein 2 (MECP2) in patients with postherpetic neuralgia (PHN). This prospective case control study enrolled 319 cases of PHN patients from April 2017~December 2019. The patients’ sleep quality and quality of life were evaluated using the Pittsburgh sleep quality score and the SF-36 scale, respectively. The serum levels of MECP2, CRP, IL-6 and TNF-α were tested using enzyme linked immunosorbent assay (ELISA). The pain condition of the patients was evaluated using the visual analogue scale (VAS). The levels of MECP2 were significantly increased in PHN patients compared with the patients without PHN. Serum MECP2 levels were the highest in patients with severe pain, and were the lowest in patients with mild pain. Similarly, the frequency of severe pain in patients with low expression of MECP2 was significantly lower than the patients with higher MECP2 expression. Besides, serum levels of inflammatory factors CRP, IL-6 and TNF-α were markedly increased in PHN patients, which were also increased with the increase of the severity of pain. CRP, IL-6 and TNF-α were positively correlated with serum levels of MECP2 in PHN patients. Before the study, patients with lower MECP2 levels showed a significantly higher SF-36 score and lower Pittsburgh and VAS scores than patients with higher levels of MECP2. However, after one month, no significant difference was found between the patients. ROC curve showed MECP2 had the potential as a diagnostic biomarker for PHN. In conclusion, higher serum MECP2 levels are associated with a more severe pain condition and increased release of inflammatory factors.

近年来,随着医学诊疗技术的不断进步,恶性肿瘤的检出率及恶性肿瘤病人的生存期均出现了较大幅度的提升,由此而导致的相关临床问题也相继增多.据统计,80％的恶性肿瘤可发生骨转移,而80％以上的骨转移发生于中轴骨 [1].骨转移引起的相关症状早已成为临床研究的热点之一,但既往国内外研究重点主要集中于易发生骨转移的恶性肿瘤种类 [2]、肿瘤骨转移机制 [3]以及骨转移的规范化治疗 [1]等,并未对恶性肿瘤中轴骨转移的临床特点进行系统分析.这导致人们对该类疾病的认识不足,常将此类疾病视为骨与软组织的慢性病变而误诊、漏诊,从而对恶性肿瘤病人生存期及生活质量产生严重的不良影响.本研究通过对126例恶性肿瘤中轴骨转移病人的临床资料进行系统分析,探讨恶性肿瘤中轴骨转移的临床特点,旨在进一步提高医务工作者对该类疾病的认识,为该类疾病的规范化治疗提供翔实的参考依据.

A visualization was provided by ultrasound imaging for nerve block, that significantly enhance its accuracy and safety. But there are challenges for the evolution and promotion of ultrasound-guided nerve block because ultrasound imaging has high variability and operator dependency. Artificial intelligence（AI） has a great develop prospect in medical ultrasound field. Based-AI system can automatically identify the target structures and real-time locate the anatomical structures by disposing, classifying and segmenting for ultrasound images,that help clinicians make up for the deficiency in anatomical theory and interpretation of ultrasound imaging,further decrease the learning curve of ultrasound-guided nerve block, that can improve the accuracy of nerve block and promote this technology to develop and popularize for better service to clinic practice. We review the current research progress of AI apply to ultrasound-guided nerve block, expecting to get some thoughts for promoting AI apply to clinic ultrasound-guided nerve block.

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.

目的:观察正清风痛宁对坐骨神经慢性缩窄性损伤(Chronic constriction injury,CCI)致小鼠神经病理性疼痛的缓解作用,并探讨其部分作用机制.方法:将30只C57BL/6小鼠随机分成3组,实验组(建模后给予正清风痛宁)、模型对照组(建模后给予生理盐水)、假手术组(术后给予生理盐水).建立小鼠神经病理性疼痛动物模型.比较三组术前及建立神经病理性疼痛模型后(术后)1、3、5、7、10、14 d小鼠的机械缩足反射阈值(paw withdrawal mechanical threshold,PWMT)、热刺激缩足反应潜伏期(paw withdrawal thermal latency,PWTL).术后14 d处死各组小鼠,ELISA检测各组小鼠脊髓组织肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)等炎症因子.结果:从CCI术后1 d开始,模型对照组小鼠的PWMT明显低于假手术组,PWTL明显短于假手术组(P<0.05).相比于模型对照组,术后第3天起给予正清风痛宁40 mg/(kg·d)后,从术后7 d起实验组小鼠的PWMT明显升高,PWTL明显延长(P<0.05).术后14 d,模型对照组小鼠脊髓中的TNF-α、IL-1β和IL-6表达水平均明显高于假手术组(P<0.05),相比于模型对照组,实验组中TNF-α、IL-1β和IL-6的表达水平均降低(P<0.05).结论:正清风痛宁对CCI致小鼠神经病理性疼痛有明显的缓解作用,其机制可能与其下调TNF-α、IL-1β、IL-6相关.

Varicella zoster virus–induced postherpetic neuralgia (PHN) can be alleviated by limited medications with serious side effects. This study aims to investigate the underlying molecular mechanism of miR-199-3p in mediating PHN in mice. 293T cells were transfected with miR-199-3p vectors (mimic/inhibitor). The target relationship between miR-199-3p and MECP2 was confirmed using luciferase reporter assay. PHN mouse model was established by RTX injection. Animal behaviors were evaluated using Hargreaves test and Von Frey test. Western blot was used for protein analysis, and quantitative reverse transcription polymerase chain reaction was performed for messenger RNA quantification. Serum levels of inflammatory mediators were determined using ELISA. Increased thermal withdrawal latency (TWL) and decreased mechanical withdrawal threshold (MWT) were observed in resiniferatoxin-induced PHN mice. Downregulated miR-199-3p and upregulated MECP2 were found in PHN mice. Upregulated miR-199-3p increased PWL and MWT, but inhibited MECP2 in PHN mice. Besides, increased miR-199-3p suppressed proinflammatory indicators and activated anti-inflammatory mediators. It also found that MECP2 was the target of miR-199-3p. Further study showed miR-199-3p enhanced PWL and MWT, and supported inflammatory response via targeting MECP2. miR-199-3p regulated inflammation by targeting MECP2 to alleviate RTX-induced PHN in mice.

原发性三叉神经痛 (idiopathic trigeminal neural-gia, ITN) 为三叉神经的一个或多个分支神经支配区的阵发性颜面部疼痛,其发病机制尚不明确,但病因假说多样,其颅脑无明显器质性病变,除三叉神经支配区疼痛外无明显的神经系统疾病症状及体征 [1].原发性三叉神经痛的终生患病率约为3～5/10万人,通常在50～70岁之间发病率最高[1,2].目前原发性三叉神经痛的治疗以药物保守治疗、微血管减压术、立体定向放射治疗及经皮穿刺射频术 (percutaneous radiofrequency thermocoagulation, PRT) 为主[2～4].微血管减压术为传统开放手术,创伤较大,且原发性三叉神经痛病人多为高龄病人,身体状况不能耐受全身麻醉手术.同时微血管减压手术后发生死亡达 0.1％,在老年病人中死亡率为0.9％,脑卒中发生率为2.5％ [5];立体定向放射治疗为无创手术方式,但高辐射量、起效慢及高复发率使其临床应用受限 [6].PRT具有创伤小、费用低及可重复操作等特点,目前逐渐成为原发性三叉神经痛的常规手术方式之一 [3].临床上多支病变的原发性三叉神经痛以(Ⅱ+Ⅲ支)常见,Kosugi等 [7]研究中(Ⅱ+Ⅲ支)原发性三叉神经痛的病人占所有研究病人的45.27％.既往对累及(Ⅱ+Ⅲ支)的原发性三叉神经痛病人多采用经卵圆孔入路半月节射频治疗,但半月节射频存在脑脊液漏、感染及出血等风险.为了减少并发症,同时随着PRT技术的不断进步以及对原发性三叉神经痛的深入理解 [8],射频靶点逐渐向外周转移,使得对累及(Ⅱ+Ⅲ支)的原发性三叉神经痛病人行经卵圆孔联合圆孔入路的高选择性周围神经射频成为可能 [9].但目前尚未见经卵圆孔半月节射频与卵圆孔联合圆孔选择性周围神经射频治疗(Ⅱ+Ⅲ支)原发性三叉神经痛的相关临床研究.