MiR-21-5p alleviates trigeminal neuralgia in rats through down-regulation of voltage-gated potassium channel Kv1.1. / MiR-21-5p通过下调电压门控钾离子通道Kv1.1è¡¨è¾¾å‡è½»å¤§é¼ ä¸‰å‰ç¥žç»ç—›.

OBJECTIVES: Trigeminal neuralgia (TN) is a common neuropathic pain. Voltage-gated potassium channel (Kv) has been confirmed to be involved in the occurrence and development of TN, but the specific mechanism is still unclear. MicroRNA may be involved in neuropathic pain by regulating the expression of Kv channels and neuronal excitability in trigeminal ganglion (TG). This study aims to explore the relationship between Kv1.1 and miR-21-5p in TG with a TN model, evaluate whether miR-21-5p has a regulatory effect on Kv1.1, and to provide a new target and experimental basis for the treatment of TN. METHODS: A total of 48 SD rats were randomly divided into 6 groups: 1) a sham group (n=12), the rats were only sutured at the surgical incision without nerve ligation; 2) a sham+agomir NC group (n=6), the sham rats were microinjected with agomir NC through stereotactic brain injection in the surgical side of TG; 3) a sham+miR-21-5p agomir group (n=6), the sham rats were microinjected with miR-21-5p agomir via stereotactic brain injection in the surgical side of TG; 4) a TN group (n=12), a TN rat model was constructed using the chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) method with chromium intestinal thread; 5) a TN+antagonist NC group (n=6), TN rats were microinjected with antagonist NC through stereotactic brain injection method in the surgical side of TG; 6) a TN+miR-21-5p antagonist group (n=6), TN rats were microinjected with miR-21-5p antagonist through stereotactic brain injection in the surgical side of TG. The change of mechanical pain threshold in rats of each group after surgery was detected. The expressions of Kv1.1 and miR-21-5p in the operative TG of rats were detected by Western blotting and real-time reverse transcription polymerase chain reaction. Dual luciferase reporter genes were used to determine whether there was a target relationship between Kv1.1 and miR-21-5p and whether miR-21-5p directly affected the 3'-UTR terminal of KCNA1. The effect of brain stereotaxic injection was evaluated by immunofluorescence assay, and then the analogue of miR-21-5p (agomir) and agomir NC were injected into the TG of rats in the sham group by brain stereotaxic apparatus to overexpress miR-21-5p. The miR-21-5p inhibitor (antagomir) and antagomir NC were injected into TG of rats in the TN group to inhibit the expression of miR-21-5p. The behavioral changes of rats before and after administration were observed, and the expression changes of miR-21-5p and Kv1.1 in TG of rats after intervention were detected. RESULTS: Compared with the baseline pain threshold, the facial mechanical pain threshold of rats in the TN group was significantly decreased from the 5th to 15th day after the surgery (P<0.05), and the facial mechanical pain threshold of rats in the sham group was stable at the normal level, which proved that the dIoN-CCI model was successfully constructed. Compared with the sham group, the expression of Kv1.1 mRNA and protein in TG of the TN group was down-regulated (both P<0.05), and the expression of miR-21-5p was up-regulated (P<0.05). The results of dual luciferase report showed that the luciferase activity of rno-miR-21-5p mimics and KCNA1 WT transfected with 6 nmol/L or 20 nmol/L were significantly decreased compared with those transfected with mimic NC and wild-type KCNA1 WT, respectively (P<0.001). Compared with low dose rno-miR-21-5p mimics (6 nmol/L) co-transfection group, the relative activity of luciferase in the high dose rno-miR-21-5p mimics (20 nmol/L) cotransfection group was significantly decreased (P<0.001). The results of immunofluorescence showed that drugs were accurately injected into TG through stereotaxic brain. After the expression of miR-21-5p in the TN group, the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were increased. After overexpression of miR-21-5p in the sham group, the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were decreased. CONCLUSIONS: Both Kv1.1 and miR-21-5p are involved in TN and miR-21-5p can regulate Kv1.1 expression by binding to the 3'-UTR of KCNA1.

Correlation between spinal cord stimulation analgesia and cortical dynamics in pain management.

AIM: Spinal cord stimulation (SCS) is an effective method to treat neuropathic pain. It is necessary to identify the responders of SCS analgesia before implantation. The aim of this study is to investigate the relationship between the cortical dynamics and SCS analgesia responders in pain management. METHODS: Resting-state EEG recording was performed in patients who underwent short-term implantation of spinal cord stimulation for pain therapy. We then did spectral analysis to capture the pattern of cortical oscillation between neuromodulation therapy analgesia responders and nonresponders. RESULTS: About 58.3% (14 out of 24) of participants were considered as analgesia responders, with average visual analogue scores reduction of 4.8 ± 1.0 after surgery, and 2.1 ± 0.7 for the nonresponder subgroup, respectively. The alpha oscillation was significantly enhanced in responder cohort compared with nonresponders. We also observed an increasing spectral power of gamma band in responders. Furthermore, the attenuation of pain severity was significantly correlated with the global alpha oscillation activity (r = 0.60, P = 0.002). Likely, positive and significant correlation was found between the pain relief and gamma activity (r = 0.58, P = 0.003). CONCLUSIONS: Distinct pattern of neural oscillation is associated with the analgesic effect of spinal cord stimulation in pain management, enhancement of cortical alpha and gamma oscillation may be a predictor of analgesia responders.

Electroencephalography Signatures for Hepatic Encephalopathy in Cirrhosis Patients Treated with Proton Pump Inhibitors: An Exploratory Pilot Study.

(1) Background: Hepatic encephalopathy (HE) is a common complication in cirrhosis patients, and recently, clinical evidence indicates that a higher risk of HE is associated with the usage of proton pump inhibitors. However, the cortical mechanism underlying this neurological disorder of HE remains unknown. (2) Methods: We review the medical recordings of 260 patients diagnosed with liver cirrhosis between January 2021 and March 2022 in one tertiary hospital. Logistic regression analyses were performed to identify the risk factor of HE development. To examine the relationship between cortical dynamics and the administration of proton pump inhibitors, resting-state electroencephalograms (EEGs) were conducted in cirrhosis patients who were treated with proton pump inhibitors. (3) Results: About 28.5% (74 out of 260) of participants developed secondary HE in this study. The logistics regression model indicated that multiple risk factors were associated with the incidence of secondary HE, including proton pump inhibitors usage, white blood cell and neutrophil counts, hemoglobin, prothrombin time activity, and blood urea nitrogen. A total of twelve cirrhosis patients who were scheduled to use proton pump inhibitors consented to performing electroencephalogram recordings upon admission, and eight of twelve participants were diagnosed with HE. Spectral analysis revealed that the decrease in alpha oscillation activities was potentially associated with the development of HE. (4) Conclusions: Our data support the susceptibility of secondary HE in cirrhosis patients treated by proton pump inhibitors. One potential cortical mechanism underlying the neurological disease is the suppression of alpha oscillations in the brain.

Clinical Outcome of Pulsed-Radiofrequency Combined With Transforaminal Epidural Steroid Injection for Lumbosacral Radicular Pain Caused by Distinct Etiology.

BACKGROUND: Lumbosacral radicular pain (LSRP) can be caused by disc herniation, spinal stenosis, and failed back surgery syndrome. The clinical effect of pulsed-radiofrequency (PRF) combined with transforaminal epidural steroid injection (TESI) for radiating pain in different population remains unclear. METHODS: We retrospectively reviewed the medical recordings of patients with LSRP caused by different etiologies, who underwent PRF and TESI treatment. The primary clinical outcome was assessed by a 10-point Visual Analog Scale (VAS) pre- and post-treatment. RESULTS: A total of 34 LSRP patients were identified and classified into 3 subgroups (disc herniation, spinal stenosis, and failed back surgery syndrome). The overall immediate pain reduction was 4.4 ± 1.1 after procedure. After a median follow-up of 9.5 months, the VAS decreased from 6.5 ± 1.0 to 2.4 ± 1.9 at the last follow-up. CONCLUSION: PRF combined with TESI is an effective approach to treat persistent LSRP in distinct population.

Prognostic Value of Immune-Inflammatory Index in PSI IV-V Patients with COVID-19.

OBJECTIVE: Respiratory failure is the leading cause of mortality in COVID-19 patients, characterized by a generalized disbalance of inflammation. The aim of this study was to investigate the relationship between immune-inflammatory index and mortality in PSI IV-V patients with COVID-19. METHODS: We retrospectively reviewed the medical records of COVID-19 patients from Feb. to Apr. 2020 in the Zhongfa Xincheng Branch of Tongji Hospital, Wuhan, China. Patients who presented high severity of COVID-19-related pneumonia were enrolled for further analysis according to the Pneumonia Severity Index (PSI) tool. RESULTS: A total of 101 patients diagnosed with COVID-19 were identified at initial research. The survival analysis revealed that mortality of the PSI IV-V cohort was significantly higher than the PSI I-III group (p = 0.0003). The overall mortality in PSI IV-V patients was 32.1% (9/28). The fatal cases of the PSI IV-V group had a higher level of procalcitonin (p = 0.022) and neutrophil-to-lymphocyte ratio (p = 0.033) compared with the survivors. Procalcitonin was the most sensitive predictor of mortality for the severe COVID-19 population with area under receiver operating characteristic curve of 0.78, higher than the neutrophil-to-lymphocyte ratio (0.75) and total lymphocyte (0.68) and neutrophil (0.67) counts. CONCLUSION: Procalcitonin and neutrophil-to-lymphocyte ratio may potentially be effective predictors for mortality in PSI IV-V patients with COVID-19. Increased procalcitonin and neutrophil-to-lymphocyte ratio were associated with greater risk of mortality.

A Prospective Study to Examine the Association of the Foramen Ovale Size with Intraluminal Pressure of Pear-Shaped Balloon in Percutaneous Balloon Compression for Trigeminal Neuralgia.

INTRODUCTION: Percutaneous balloon compression (PBC) is an effective and safe option for patients with trigeminal neuralgia. A pear-shaped balloon can be used to identify the proper compression of the Gasserian ganglion during the PBC procedure. The aim of this study was to evaluate the relationship between the foramen ovale (FO) size and intraluminal pressure of the pear-shaped balloon. METHODS: Thirteen patients that presented with classical trigeminal neuralgia were scheduled to undertake PBC surgery at the Pain Department of the Third Xiangya Hospital, Central South University, from November 2020 to April 2021. Three-dimensional computed tomography reconstruction of the skull base was performed to capture the feature of FO preoperatively. The intraluminal pressure was continuously recorded when a pear-shaped balloon was obtained during the procedure. Correlation analysis was calculated to determine the association of the intraluminal balloon pressure with FO parameter. RESULTS: All participants reported complete relief of pain at discharge. The enduring analgesic effect of PBC was maintained in all patients with a median follow-up up to 5.5 months (range, 3-8 months). The average intraluminal balloon pressure was 161.5 ± 29.4 kPa at the initial compression (P1), and 134.8 ± 21.5 kPa at the ending of compression (P2), respectively. P1 was significantly correlated with the length (r = 0.61, P = 0.024) of FO. Similarly, a significant and positive correlation was observed between P2 and the length (r = 0.63, P = 0.022) of FO. CONCLUSIONS: Preoperative assessment of FO may be a potential predictor of intraluminal pressure to reach a pear-shaped balloon during PBC treatment. Narrow FO is associated lower intraluminal balloon pressure.

Implantable Peripheral Nerve Stimulation for Trigeminal Neuropathic Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: Implantable peripheral nerve stimulation has been increasingly used to treat neuropathic pain. This neuromodulation strategy may be an alternative option for intractable trigeminal neuropathic pain; however, evidence for this treatment approach remains limited. A systematic review was conducted to identify studies of patients that underwent peripheral nerve stimulation implantation for trigeminal neuropathic pain. MATERIALS AND METHODS: Databases including, PubMed, EMBASE, and Cochrane Library were searched up to October 5, 2020. The primary outcomes were changes in pain scores and response rates of neuromodulation therapy. A random effects model was used for meta-analysis. Subgroup analysis was performed to examine the source of heterogeneity. RESULTS: Thirteen studies including 221 participants were evaluated. The estimated response rate of neuromodulation treatment was 61.3% (95% CI: 44.4-75.9%, I2  = 70.733%, p < 0.0001) at the last follow-up. The overall reduction in pain scores was 2.363 (95% CI: 1.408-3.319, I2  = 85.723%, p < 0.0001). Subgroup analysis further confirmed that stimulation target (peripheral branch vs. trigeminal ganglion vs. trigeminal nerve root) contributed the heterogeneity across enrolled studies. Better clinical outcome was associated with stimulation of the trigeminal peripheral branch (p < 0.0001). CONCLUSION: Peripheral nerve stimulation may be a promising approach in the management of trigeminal neuropathic pain, especially for patients intractable to conventional therapy.

Clinical and Radiological Comparisons of Percutaneous Low-Power Laser Discectomy and Low-Temperature Plasma Radiofrequency Ablation for Cervical Radiculopathy: A Prospective, Multicenter, Cohort Study.

BACKGROUND: Minimally invasive techniques, such as percutaneous low-power laser discectomy (PLLD) and low-temperature plasma radiofrequency ablation (coblation) can be applied to treat degenerative cervical radiculopathy. However, less evidence supports the superiority of distinct minimally-invasive therapy. Our study aimed to evaluate the clinical and radiological characteristics of the PLLD and coblation for cervical radiculopathy. METHODS: This was a prospective, multicenter, cohort study (ChiCTR-ONC-17010356). The modified Macnab criteria was performed to assess the clinical improvement pre- and post-surgery. To evaluate the radiological effect, the Pfirrmann grading system and disk herniation index were applied with MRI. RESULTS: In this study, 28 patients were enrolled in the coblation group and 30 patients in the PLLD group. The mean good-excellent rate at 3-month follow-up was 82.1% for PLLD group, and 66.7% for coblation group, respectively (p = 0.179). The PLLD group achieved higher good-excellent rate 6 and 12 months after discharge (92.9 vs. 70.0%, p = 0.026). Radiological data revealed that PLLD but not coblation treatment achieved significant reduction of disk herniation index (p < 0.0001). Coblation treatment did not change the Pfirrmann grades of cervical radiculopathy patients (n = 18), and 7 out of 17 (41.2%) patients achieved improvement after PLLD therapy. None obvious adverse event was observed in this study. CONCLUSION: Both PLLD and coblation are effective and safe option for patients with cervical radiculopathy. Better long-term clinical outcomes may be potentially associated with the improvement of disk degeneration after PLLD treatment.

Clinical Efficacy of Short-Term Peripheral Nerve Stimulation in Management of Facial Pain Associated With Herpes Zoster Ophthalmicus.

OBJECTIVE: Peripheral nerve stimulation may be an alternative option to treat severe facial pain. We assessed the application of peripheral nerve stimulation for pain management in patients with herpes zoster ophthalmicus. METHOD: A retrospective analysis was conducted in patients suffering severe facial pain caused by ophthalmic herpetic lesions. We identified the change in pain severity before and after peripheral nerve stimulation for up to 12 months. RESULTS: Eighteen patients were enrolled. Their mean age was 70.8 ± 9.5 years. Fifteen patients presented with subacute pain for 1-3 months, and three patients suffered postherpetic neuralgia. Dramatic relief from pain was achieved in 83% of patients (15 out of 18) upon initial removal of the stimulator, with pain reduction of > 50%. The long-term analgesic effect was reported at the 6- and 12-month follow-ups, with reductions in the visual analog scale of 4.8 ± 1.2 (n = 18) and 5.4 ± 1.4 (n = 11), respectively. The prevalence of postherpetic neuralgia was 7% (1 out of 15) in the subacute pain group. No obvious adverse effect was observed. CONCLUSION: Peripheral nerve stimulation may be an efficacious and safe approach for pain control in patients with herpes zoster ophthalmicus.

Basic fibroblast growth factor attenuates the degeneration of injured spinal cord motor endplates.

The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Allen's method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also well recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additionally, anterior tibial muscle fibers slowly, but progressively, atrophied. nohistochemical staining showed that the absorbance values of calcitonin gene related peptide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic broblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related peptide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through attenuating the decreased expression of calcitonin gene related peptide and acetylcholinesterase in anterior horn motor neurons of the injured spinal cord.