Clinical efficacy of transforaminal endoscopic discectomy in the treatment of recurrent lumbar disc herniation: a single-center retrospective analysis.

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.

Oxidative stress induced by NOX2 contributes to neuropathic pain via plasma membrane translocation of PKCε in rat dorsal root ganglion neurons.

BACKGROUND: Nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-induced oxidative stress, including the production of reactive oxygen species (ROS) and hydrogen peroxide, plays a pivotal role in neuropathic pain. Although the activation and plasma membrane translocation of protein kinase C (PKC) isoforms in dorsal root ganglion (DRG) neurons have been implicated in multiple pain models, the interactions between NOX2-induced oxidative stress and PKC remain unknown. METHODS: A spared nerve injury (SNI) model was established in adult male rats. Pharmacologic intervention and AAV-shRNA were applied locally to DRGs. Pain behavior was evaluated by Von Frey tests. Western blotting and immunohistochemistry were performed to examine the underlying mechanisms. The excitability of DRG neurons was recorded by whole-cell patch clamping. RESULTS: SNI induced persistent NOX2 upregulation in DRGs for up to 2 weeks and increased the excitability of DRG neurons, and these effects were suppressed by local application of gp91-tat (a NOX2-blocking peptide) or NOX2-shRNA to DRGs. Of note, the SNI-induced upregulated expression of PKCε but not PKC was decreased by gp91-tat in DRGs. Mechanical allodynia and DRG excitability were increased by ψεRACK (a PKCε activator) and reduced by εV1-2 (a PKCε-specific inhibitor). Importantly, εV1-2 failed to inhibit SNI-induced NOX2 upregulation. Moreover, the SNI-induced increase in PKCε protein expression in both the plasma membrane and cytosol in DRGs was attenuated by gp91-tat pretreatment, and the enhanced translocation of PKCε was recapitulated by H2O2 administration. SNI-induced upregulation of PKCε was blunted by phenyl-N-tert-butylnitrone (PBN, an ROS scavenger) and the hydrogen peroxide catalyst catalase. Furthermore, εV1-2 attenuated the mechanical allodynia induced by H2O2 CONCLUSIONS: NOX2-induced oxidative stress promotes the sensitization of DRGs and persistent pain by increasing the plasma membrane translocation of PKCε.

Silencing of lncRNA Gm14461 alleviates pain in trigeminal neuralgia through inhibiting astrocyte activation.

Our previous study showed that silencing of lncRNA Gm14461 alleviated pain in a murine model of trigeminal neuralgia (TN), but the molecular mechanism remains not fully understood. Evidence indicates that astrocyte activation and autophagy are involved in the development of TN. Herein, this study aimed to elucidate whether the pain-relief effect of Gm14461 silencing in TN involved regulation of astrocyte activation and autophagy. A murine model of TN was induced by chronic constriction injury of the infraorbital nerve surgery. The mechanical withdrawal threshold (MWT) was measured to assess the analgesic effect of Gm14461 silencing. Mouse astrocytes were treated with lipopolysaccharide (LPS) as a cell model. Astrocyte activation was evaluated by glial fibrillary acidic protein (GFAP) immunofluorescence and western blot analysis of GFAP. Autophagy was evaluated by LC3 immunofluorescence and western blot analysis of autophagy-related proteins. The results showed that Gm14461 silencing increased MWT value in TN model mice. Meanwhile, Gm14461 silencing inhibited astrocyte activation and enhanced autophagy in both TN mice and LPS-treated astrocytes. The enhancement of autophagy by Gm14461 silencing involved the activation of the AMPK signaling and the suppression of the Akt/mTOR signaling. Collectively, the analgesic effect of Gm14461 silencing in TN was related to attenuation of astrocyte activation via enhancement of autophagy.

Different approaches to percutaneous endoscopic lumbar discectomy for L5/S1 lumbar disc herniation: a retrospective study.

OBJECTIVE: To observe the surgical procedure and outcome of percutaneous endoscopic lumbar discectomy for L5/S1 lumbar disc herniation (LDH) by the interlaminar and transforaminal approach. METHODS: A total of 153 patients with L5/S1 LDH who were treated using percutaneous endoscopic transforaminal discectomy (PETD, n = 84) or percutaneous endoscopic interlaminar discectomy (PEID, n = 69) from January 2016 to January 2018 were enrolled in this retrospective study. The time of puncture, operation under the endoscope, total operation and number of fluoroscopy of the two groups were compared. All groups were followed up for two years by using the Oswestry disability index (ODI) and the Visual Analogue Scale (VAS). Additionally, the incidence of complications, reoperation and postoperative low back pain were compared between the two groups. RESULTS: There were no significant difference in general information between the two groups. Compared to the PEID group, the PETD group had a decreased operation time under the endoscope and an increased puncture time, total operation time, and the number of fluoroscopy (p < 0.05). The preoperative VAS and ODI scores of the PETD and PEID group were decreased at the last follow-up (p < 0.05). There were no difference in the preoperative or last follow-up VAS and ODI scores, as well as complications, reoperation between the two groups (p > 0.05). The incidence of postoperative low back pain in the PETD group was lower than that in the PEID group (p > 0.05). CONCLUSIONS: The two-year clinical outcome of PETD is equal to that of PEID for L5/S1 LDH. Compared to those with PETD, the puncture time, total operation time and radiation exposure are lower with PEID, but the incidence of postoperative low back pain is higher.

Nerve injury elevates functional Cav3.2 channels in superficial spinal dorsal horn.

Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properties of Cav3 channels in superficial spinal dorsal horn. Our in vivo studies showed that the blockers of Cav3 channels robustly alleviated PSNL-induced mechanical allodynia and thermal hyperalgesia, which lasted at least 14 days following PSNL. Meanwhile, PSNL triggered an increase in both mRNA and protein levels of Cav3.2 but not Cav3.1 or Cav3.3 in rats. However, in Cav3.2 knockout mice, PSNL predominantly attenuated mechanical allodynia but not thermal hyperalgesia. In addition, the results of whole-cell patch-clamp recordings showed that both the overall proportion of Cav3 current-expressing neurons and the Cav3 current density in individual neurons were elevated in spinal lamina II neurons from PSNL rats, which could not be recapitulated in Cav3.2 knockout mice. Altogether, our findings reveal that the elevated functional Cav3.2 channels in superficial spinal dorsal horn may contribute to the mechanical allodynia in PSNL-induced neuropathic pain model.

Causal relationship between coffee intake and neurological diseases: a Mendelian randomization study.

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.

Posterior Percutaneous Endoscopic Cervical Discectomy for Single-Level Soft, Huge Central Disc Herniation.

BACKGROUND: Posterior percutaneous endoscopic cervical discectomy (PPECD) has been proven safe and effective for foraminal cervical disc herniation (CDH). However, central CDH has long been considered as the contraindication of PPECD, because the path is obstructed by the spinal cord and nerve root. OBJECTIVES: To preliminarily assess the feasibility, safety, and effectiveness of PPECD for single-level soft, huge central CDH. STUDY DESIGN: A retrospective cohort study. SETTING: Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College). METHODS: Between 2017 and 2020, 31 patients diagnosed with single-level soft, huge central CDH were treated by PPECD. Primary outcomes included the measures of neck and radicular pain based on the numeric rating scale (NRS) and cervical neurologic status based on the Japanese Orthopedic Association (JOA) score. The global outcome was assessed using the Odom's criteria at one-year follow-up. RESULTS: Compared to the baseline, there was a constant and significant reduction of NRS-rated pain and improvement of JOA-rated cervical neurologic status postoperatively (P < 0.01). According to the Odom's criteria, 96.8% (30/31) of patients had satisfactory postoperative clinical improvement (excellent or good outcomes) at one-year follow-up. Complications included C5 nerve root palsy and spinal cord injury. The total complication rate was 16.5% (2/31), but these complications were temporary and not catastrophic. LIMITATIONS: The limitations of this study include the volume of the sample, a short follow-up period, and the lack of a control group. CONCLUSIONS: Our preliminary experience indicates that PPECD is a feasible and promising alternative for symptomatic single-level soft, huge central CDH.

HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.

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.

DHT inhibits REDOX damage and neuroinflammation to reduce PND occurrence in aged mice via mmu_circ_0001442/miR-125a-3p/NUFIP2 axis.

BACKGROUND: Perioperative neurocognitive disorder (PND) is the main cause of poor postoperative recovery in elderly patients with age-related reductions in androgen levels. However, the underlying mechanisms have not been completely elucidated. METHODS: A mouse model of PND was constructed using abdominal surgery. Dihydrotestosterone (DHT), as the primary androgen, can improve the cognitive function of mice with PNDs by reducing REDOX damage. To clarify the role of circular RNA (circRNA) in DHT in improving cognitive function in mice with PND, circRNA sequencing was performed to analyze the expression of circRNA in the hippocampus of mice. RESULTS: We confirmed that mmu_circ_0001442 is the primary circRNA responsive to DHT stimulation in mice with PND. The mmu_circ_0001442/miR-125a-3p/NUFIP2 axis was predicted and constructed according to the analysis of databases, including pita, miRanda, TargetScan, miRDB, micro-CDS, PolymiRTS, and TarBase v.8. Subsequently, the axis was verified by qPCR and double-luciferase reporter gene assays. In vitro, we found that DHT rarely had an effect on the growth of BV2 cells using the CCK-8 assay, but it attenuated the cytotoxic effect of lipopolysaccharide (LPS) on BV2 cells. In addition, we found that LPS stimulation promoted the release of proinflammatory cytokines, including IL-6 and TNF-α, in BV2 cells, whereas mmu_circ_0001442 knockdown and NUFIP2 knockdown partially abrogated this effect. CONCLUSIONS: Taken together, DHT inhibited REDOX damage and neuroinflammation in the hippocampus to alleviate cognitive disorders in mice with PNDs via activation of the mmu_circ_0001442/miR-125a-3p/NUFIP2 axis. This study provides a novel rationale for developing DHT as a potential therapeutic agent for PND prevention.

Exploring gene signatures and regulatory networks in a rat model of sciatica: implications and validation in neuropathic pain.

Background: Sciatica (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. Methods: Sciatic 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. Results: The 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-1ß, MCP-1, and IL-6, and microglial cell activation in the spinal dorsal horn. ELISA results confirmed the increased levels of IL-1ß, MCP-1, and IL-6 in the spinal dorsal horn. Conclusion: These 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.

Nomogram for predicting the unfavourable outcomes of percutaneous endoscopic transforaminal discectomy for lumbar disc herniation: a retrospective study.

Objective: To investigate and integrate multiple independent risk factors to establish a nomogram for predicting the unfavourable outcomes of percutaneous endoscopic transforaminal discectomy (PETD) for lumbar disc herniation (LDH). Methods: From January 2018 to December 2019, a total of 425 patients with LDH undergoing PETD were included in this retrospective study. All patients were divided into the development and validation cohort at a ratio of 4:1. Univariate and multivariate logistic regression analyses were used to investigate the independent risk factors associated with the clinical outcomes of PETD for LDH in the development cohort, and a prediction model (nomogram) was established to predict the unfavourable outcomes of PETD for LDH. In the validation cohort, the nomogram was validated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA). Results: 29 of 340 patients showed unfavourable outcomes in the development cohort, and 7 of 85 patients showed unfavourable outcomes in the validation cohort. Body mass index (BMI), course of disease (COD), protrusion calcification (PC), and preoperative lumbar epidural steroid injection (LI) were independent risk factors associated with the unfavourable outcomes of PETD for LDH and were identified as predictors for the nomogram. The nomogram was validated by the validation cohort and showed high consistency (C-index = 0.674), good calibration and high clinical value. Conclusions: The nomogram based on patients' preoperative clinical characteristics, including BMI, COD, LI and PC, can be used to accurately predict the unfavourable outcomes of PETD for LDH.

[Retracted] Role of microRNA­210 in human intervertebral disc degeneration.

[This retracts the article DOI: 10.3892/etm.2016.3176.].

Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus.

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.

Bioinformatics Analysis of the MicroRNA-Metabolic Gene Regulatory Network in Neuropathic Pain and Prediction of Corresponding Potential Therapeutics.

Neuropathic pain (NP) involves metabolic processes that are regulated by metabolic genes and their non-coding regulator genes such as microRNAs (miRNAs). Here, we aimed at exploring the key miRNA signatures regulating metabolic genes involved in NP pathogenesis. We downloaded NP-related data from public databases and identified differentially expressed microRNAs (miRNAs) and mRNAs through differential gene expression analysis. The miRNA target prediction was performed, and integration with the differentially expressed metabolic genes (DEMGs) was used for constructing the miRNA-DEMG network. Subsequently, functional enrichment analysis and protein-protein interaction (PPI) analysis were performed to explore the role of DEMGs in the regulatory network. The drug prediction was performed based on the DEMGs in the miRNA-DEMG network. A total of 8251 differentially expressed mRNAs (4193 upregulated and 4058 downregulated), and 959 differentially expressed miRNAs (455 upregulated and 504 downregulated) were identified. Moreover, after target gene prediction, a miRNA-DEMG network composed of 22 miRNAs and 113 mRNAs was constructed. The network was constituted of 135 nodes and 236 edges. We found that DEMGs in the network were mainly enriched in metabolic pathways and metabolic processes. A total of 1200 drugs were predicted as potential therapeutics for NP based on the differentially expressed genes, while 170 drugs were predicted for the DEMGs in the miRNA-DEMG network. Conclusively, our study predicted drugs that may be effective against the metabolic changes induced by miRNA dysregulation in NP. This information will help further reveal the pathological mechanism of NP and provide more treatment options for NP patients.

MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate TRX-Induced PHN in Mice.

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 TRX 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. Paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) were decreased 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 TRX-induced PHN in mice.

Cost-effectiveness analysis of 5% lidocaine-medicated plaster compared with pregabalin for the treatment of post-herpetic neuralgia in China.

BACKGROUND: Post-herpetic neuralgia (PHN) is the most common complication of herpes zoster and is defined as pain that lasts for one month or more after the outbreak itself heals. While the annual incidence of herpes zoster is approximately 3-5%, 9-34% of these patients will develop PHN. Approximately 30-50% of these cases last for more than a year but some cases can persist for 10 years or more. To date, the economic burden of PHN in China has not been studied. The first-line topical therapy for PHN is application of lidocaine-medicated plasters (LMPs) which have shown good efficacy and tolerability. Furthermore, LMPs were added to China's National Health Insurance List in 2019, thereby significantly relieving the financial burden on patients. A cost-effectiveness analysis was performed on LMPs compared with pregabalin in the treatment of PHN to provide a reference for the basis for clinical treatments and health decisions in patients with PHN. METHODS: A Markov model was built according to the PHN disease characteristics. The efficacy data were extracted from a randomized controlled trial conducted in China, and the transition probability, utility value, and medical cost of each state in the model were collected through a systematic review of the literature and public databases. The outcome measure was cost per quality-adjusted life year (QALY) gained. The incremental cost-effectiveness ratios (ICERs) were calculated. Sensitivity analysis was conducted to confirm the robustness of the model. RESULTS: In the base case analysis, treatment for a 6-month period with pregabalin and lidocaine plasters led to a mean QALY gain of 0.34012 and 0.42543, respectively, and mean incremental costs of 5,720 Chinese Yuan (CNY) and 3690 CNY, respectively. The ICER of treatment with 5% lidocaine plaster was negative, indicating that lidocaine plasters had absolute advantage. Monte Carlo simulation resulted in an estimate of 90% probability that the 5% lidocaine plaster treatment was cost-effective. CONCLUSIONS: Within the Chinese medical and health system, LMPs can reduce the economic burden of patients with PHN. LMPs are more cost-effective and more efficient in absolute terms compared to the first-line treatment systemic drug pregabalin in the treatment of PHN.

Effects of Pulsed Radiofrequency on Nerve Repair and Expressions of GFAP and GDNF in Rats with Neuropathic Pain.

OBJECTIVE: To study the effect of pulsed radio frequency (PRF) on nerve repair and the expression of GFAP and GDNF in rats with neuropathic pain. METHODS: Thirty SPF healthy SD rats were randomly divided into control group (Group C), PSNL group (partial ligation of sciatic nerve) + sham group (Group PS), and PSNL group (partial ligation of sciatic nerve) + PRF group (Group PR), with 10 rats in each group. In group C, the right sciatic nerve was exposed without ligation. In the PS group, the model of neuropathic pain was established by partial ligation of sciatic nerve. The mice in the PR group were treated with PRF after establishing the neuropathic pain model. The general behavior of rats during the treatment was observed. The mechanical and thermal hyperalgesia were measured before operation and 1, 3, 7, and 14 days after operation. The content of inflammatory factors in nerve tissue was detected by ELISA. The pathological condition of nerve tissue was observed by HE. The gene and protein changes of GFAP and GDNF in nerve tissue were determined by QRT PCR and Western blot. RESULTS: Rats in the control group were free to move and in good condition. In the PS group, there were different degrees of claudication, weakness of the lower limbs, lateral toe valgus, nerve injury, and other behavioral changes. After the pulsed radiofrequency in the PR group, the above symptoms decreased gradually with the prolongation of the treatment time. The mechanical pain sensitivity and thermal allodynia of the PS group were reduced after the operation. The mechanical pain sensitivity and thermal pain sensitivity of the PR group gradually increased with the prolongation of the treatment time, and the 14 days were basically close to the control group. The levels of TNF-α and IL-6 in ELISA were significantly higher in the PS group than in the control group, and the content in the PR group was gradually reduced, which was close to the control group. HE staining showed that the sciatic nerve fibers disappeared, and the formation of nerve cavities was obvious in the 14-day PS group. The nerve fibers were found in the sciatic tissue of the PR group, and there was no obvious hemorrhagic edema and cell deformation. The expression of GFAP mRNA in the PS group was significantly higher than that in the control group and the PR group (p < 0.05), and the expression of GDNF was opposite (p < 0.05). The results of western blot showed that the expression of GFAP protein in the 14-day PS group was significantly higher than that in the control group. The expression of the PR group decreased compared with the control group, and the expression of GDNF was opposite (p < 0.05). CONCLUSION: Pulsed radiofrequency ablation can promote neurological repair, promote GDNF, and reduce the expression of GFAP in rats with neuropathic pain.

Low-Dose Collagenase Chemonucleolysis Combined with Radiofrequency in the Treatment of Lumbar Disc Herniation: A 10-Year Retrospective Study.

OBJECTIVE: This study explored the 10-year efficacy, safety, and prognostic factors of low-dose collagenase chemonucleolysis (CCNL) combined with radiofrequency (RF) in the treatment of lumbar disc herniation (LDH). METHODS: The data of 167 LDH patients were collected. Modified MacNab criteria, Numerical Rating Scale (NRS), and Japanese Orthopedic Association (JOA) scores were, respectively, used to evaluate patients' excellent and good rates, pain degree, and nerve function. The preoperative and 10-year postoperative patients' pain, numbness, and muscle weakness were compared. Patients' complications in perioperative period, recurrent/reappeared LDH, and reoperations were recorded. Finally, the independent risk factors affecting the long-time efficacy were assessed. RESULTS: A total of 126 patients were included. The patients' excellent and good rates were 86.51%-92.86% with no significant difference (P > 0.05). Postoperative NRS and JOA scores significantly improved (P < 0.01), most obvious within 6 months postoperatively. At 10 years postoperatively, 65.08%, 83.95%, and 93.02% of patients' pain, numbness, and muscle weakness were completely relieved (P < 0.05). Perioperative complications occurred in three patients with the rate of 2.38%. Recurrent/reappeared LDH patients were 11 with the ratio of 8.73%; nine of them underwent reoperations with the rate of 7.14%. And patients' probability of fair and poor efficacy at 10 years postoperatively with the course of disease >12 months and the responsibility disc ≥2 were, respectively, 6.005 and 4.227 times that of patients with the course of disease ≤12 months and the responsibility disc = 1 (P < 0.05). CONCLUSION: The combined treatment is effective and safe in the long term. A course of disease >12 months and responsibility disc ≥2 independently reduce efficacy, and a course of disease >12 months has a more significant impact.

Electrophysiological and Morphological Features of Rebound Depolarization Characterized Interneurons in Rat Superficial Spinal Dorsal Horn.

Substantia gelatinosa (SG) neurons, which are located in the spinal dorsal horn (lamina II), have been identified as the "central gate" for the transmission and modulation of nociceptive information. Rebound depolarization (RD), a biophysical property mediated by membrane hyperpolarization that is frequently recorded in the central nervous system, contributes to shaping neuronal intrinsic excitability and, in turn, contributes to neuronal output and network function. However, the electrophysiological and morphological properties of SG neurons exhibiting RD remain unclarified. In this study, whole-cell patch-clamp recordings were performed on SG neurons from parasagittal spinal cord slices. RD was detected in 44.44% (84 out of 189) of the SG neurons recorded. We found that RD-expressing neurons had more depolarized resting membrane potentials, more hyperpolarized action potential (AP) thresholds, higher AP amplitudes, shorter AP durations, and higher spike frequencies in response to depolarizing current injection than neurons without RD. Based on their firing patterns and morphological characteristics, we propose that most of the SG neurons with RD mainly displayed tonic firing (69.05%) and corresponded to islet cell morphology (58.82%). Meanwhile, subthreshold currents, including the hyperpolarization-activated cation current (I h ) and T-type calcium current (I T ), were identified in SG neurons with RD. Blockage of I h delayed the onset of the first spike in RD, while abolishment of I T significantly blunted the amplitude of RD. Regarding synaptic inputs, SG neurons with RD showed lower frequencies in both spontaneous and miniature excitatory synaptic currents. Furthermore, RD-expressing neurons received either Aδ- or C-afferent-mediated monosynaptic and polysynaptic inputs. However, RD-lacking neurons received afferents from monosynaptic and polysynaptic Aδ fibers and predominantly polysynaptic C-fibers. These findings demonstrate that SG neurons with RD have a specific cell-type distribution, and may differentially process somatosensory information compared to those without RD.