摘要
Introduction Trigeminal neuralgia is a painful neuropathic disorder characterized by sudden electric shocklike pain that significantly impacts patients' quality of life. Multiple treatment alternatives are available, including medical and surgical options but establishing the optimal course of action can be challenging. To enhance clinical decision-making for trigeminal neuralgia treatment, it is imperative to organize, describe and map the available systematic reviews and randomized trials. This will help identify the best treatment alternatives supported by evidence and acknowledge potential knowledge gaps where future research is needed. Objective This systematic mapping review aims to provide up-to-date evidence on the different surgical and pharmacological treatment alternatives used for trigeminal neuralgia. Methods A search will be systematically conducted on the Epistemonikos database to identify potentially eligible systematic reviews. Additionally, a search will be made in PubMed, CENTRAL, and EBSCO to identify randomized controlled trials assessing pharmacological and surgical treatment interventions for trigeminal neuralgia. Two independent reviewers will screen and select the studies. Data on the different treatment alternatives and reported outcomes in the included studies will be extracted using standardized forms. Following extraction, descriptive statistical methods will be used to analyze the data. The final output of this study will include an evidence map that will illustrate the connections between different treatments and their respective outcomes, providing a clear depiction of the evidence landscape. Expected results This study expects to map, describe and assess the methodological quality of the available systematic reviews and trials on pharmacological interventions and neurosurgical procedures for treating trigeminal neuralgia. It will present the results in an evidence map that organizes the available evidence based on their different interventions and outcomes. This evidence map will serve as a visual tool to assist healthcare professionals and patients to understand evidence-based treatment options and their implications for managing this medical condition.
Introducción La neuralgia del trigémino es un trastorno neuropático doloroso caracterizado por un dolor súbito y agudo, similar a una descarga eléctrica, que impacta significativamente en la calidad de vida. Dada la variedad de tratamientos disponibles, médicos y quirúrgicos, es crucial organizar y mapear la evidencia proveniente de revisiones sistemáticas y ensayos clínicos para orientar las decisiones clínicas. Esto permite identificar tratamientos respaldados por evidencia y señalar áreas de investigación futura. Objetivo El propósito de esta revisión sistemática de mapeo es proporcionar una visión actualizada de la evidencia existente en relación con las diversas opciones de tratamiento quirúrgico y farmacológico empleadas en el manejo de la neuralgia del trigémino. Métodos Se realizará una búsqueda sistemática en la base de datos Epistemonikos para identificar potenciales revisiones sistemáticas. Adicionalmente, se buscará en PubMed, CENTRAL y EBSCO ensayos clínicos aleatorizados que evalúen intervenciones de tratamiento farmacológico y quirúrgico para la neuralgia del trigémino. Dos revisores independientes cribarán y seleccionarán los estudios. Se extraerán datos sobre las diferentes alternativas de tratamiento y los resultados reportados en los estudios incluidos utilizando formularios estandarizados. Tras la extracción, se utilizarán métodos estadísticos descriptivos para analizar los datos. El producto final de este estudio incluirá un mapa de evidencia que ilustrará las conexiones entre los diferentes tratamientos y sus respectivos resultados, proporcionando una representación clara del panorama de la evidencia. Resultados esperados Los resultados que se extraerán de este mapeo sistemático incluyen identificar y describir las diferentes alternativas, tanto farmacológicas como quirúrgicas, que existen para el tratamiento de la neuralgia del trigémino. Además, se planea presentar un mapa de evidencia que se basará en los ensayos clínicos aleatorizados y revisiones sistemáticas, el cual mostrará la evidencia de manera organizada entre las diferentes intervenciones y sus desenlaces. Este mapa de evidencia servirá como una herramienta visual que ayudará a los profesionales de la salud y los pacientes a comprender mejor las opciones de tratamiento respaldadas por la evidencia y sus consecuencias en el manejo de esta condición médica.
摘要
El dolor neuropático es común en la práctica clínica. Se estima que afecta entre el 2 y 3 % de la población a nivel global. Una cantidad considerable de pacientes presentan dolor refractario a tratamientos existentes, volviéndolo un reto diagnóstico y terapéutico. El objetivo de este estudio es describir el uso clínico de lidocaína intravenosa para manejo de dolor neuropático no oncológico en adultos. La búsqueda de información se realizó consultando las bases de datos HINARI, SciELO y PubMed. Se seleccionaron artículos en inglés y español de 2017 a 2021. Se utilizaron artículos originales, ensayos clínicos, revisiones bibliográficas y metaanálisis. Las causas de dolor neuropático en las que ha sido utilizada la lidocaína son la neuralgia posherpética, neuropatía diabética y neuralgia del trigémino. El uso de lidocaína intravenosa demostró que disminuye la intensidad del dolor; sin embargo, al compararlo con otros fármacos de primera línea no hay diferencias a largo plazo. La mayoría de efectos secundarios se presentan en el sistema nervioso, gastrointestinal y cardiovascular. La lidocaína intravenosa como monoterapia para manejo de dolor neuropático no oncológico, si bien fue eficaz a corto plazo con dosis de 3-5 mg/Kg, no tuvo un efecto persistente y duradero
Neuropathic pain is common in clinical practice; it is estimated that 2 to 3 % of the global population is affected; a considerable number of patients present pain refractory to existing treatments, making it a diagnostic and therapeutic challenge. The objective of this study is to describe the clinical use of intravenous lidocaine for the management of non-cancer neuropathic pain in adults. The information search was performed by consulting the HINARI, SciELO and PubMed databases. Articles with an obsolescence of no more than five years, both in English and Spanish, were selected. Original articles, clinical trials, bibliographic reviews and meta-analyses were used. The causes of neuropathic pain in which lidocaine has been used were postherpetic neuralgia, diabetic neuropathy, and trigeminal neuralgia. The use of intravenous lidocaine has been shown to decrease pain intensity; however, when compared with other first line drugs, there are no long-term differences. Most side effects occur in the nervous, gastrointestinal, and cardiovascular systems. Intravenous lidocaine as monotherapy for the management of non-cancer neuropathic pain, although effective in the short term with doses of 3-5 mg/Kg, does not have a persistent and long-lasting effect
Subject(s)
Pain Management , Adult , El Salvador摘要
Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.
摘要
Objective:The activation of astrocytes is an important process in the formation of chronic pain.This study aims to observe the activation of A1 reactive astrocytes in the medullary dorsal horn in the rat model of trigeminal neuralgia,and to explore the mechanism of central sensitization caused by A1 reactive astrocyte. Methods:The adult male rats were randomly divided into a sham group and a chronic constriction injury of infraorbital nerve(ION-CCI)group.The facial mechanical pain threshold and thermal withdrawal latency were measured before the operation and on the 1st,3rd,7th,10th,and 14th day after the operation.After pain behavior observation,the expression of glial fibrillary acidic protein(GFAP)in the medullary dorsal horn was observed by immunohistochemistry and immunofluorescence colocalization of GFAP,complement 3(C3)/S100A10,and 4',6-diamidino-2-phenylindole(DAPI)was analyzed.Primary astrocytes were cultured and randomly divided into a naive group and a DHK group.The DHK group was treated with 1 mmol/L of astrocyte activation inhibitor dihydrokainic acid(DHK).Fura-2/AM was used to stain the astrocytes and the calcium wave of the 2 groups under the stimulation of high potassium was recorded and compared.The expression of C3 was detected by Western blotting. Results:The facial mechanical pain threshold and thermal withdrawal latency of the ION-CCI group were significantly lower than those of the sham group(both P<0.05).There were a large number of GFAP positive astrocytes in the medullary dorsal horn of the ION-CCI group.The fluorescence intensity of GFAP in the ION-CCI group was higher than that in the sham group(P<0.05).GFAP and C3/S100A10 were co-expressed in astrocytes.Compared with the sham group,the fluorescence intensity of C3 and the protein expression of C3 in the ION-CCI group were increased(both P<0.05).The expression of C3 in ION-CCI group was significantly increased(P<0.05).Compared with the naive group,the C3 protein expression was significantly decreased in the DHK group(P<0.05).The intensity of calcium fluorescence was increased after high potassium stimulation in both groups.Furthermore,the peak and increase amplitude of calcium fluorescence in the naive group were much higher than those in the DHK group(both P<0.05). Conclusion:A1 reactive astrocytes in the medullary dorsal horn of trigeminal neuralgia model rats are increased significantly,which may participate in central sensitization of trigeminal neuralgia by impacting astrocyte calcium wave.
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Objective: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. Conclusion: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.
摘要
Objective:There are a variety of minimally invasive interventional treatments for trigeminal neuralgia,and the efficacy evaluation is different.The preferred treatment scheme is still controversial.This study aims to investigate the differences in treatment effects between patients with primary trigeminal neuralgia(PTN)treated with percutaneous balloon compression(PBC)for the first intervention and patients with pain recurrence after radiofrequency thermocoagulation(RT)who then received PBC for PTN,and to offer clinicians and patients more scientifically grounded and precise treatment alternatives. Methods:We retrospectively analyzed 103 patients with PTN admitted to the Department of Pain Management of the Second Affiliated Hospital of Guangxi Medical University from January 2020 to December 2021,including 49 patients who received PBC for the first time(PBC group)and 54 patients who received PBC for pain recurrence after RT(RT+PBC group).General information,preoperative pain score,intraoperative oval foramen morphology,oval foramen area,balloon volume,duration of compression,and postoperative pain scores and pain recurrence at each time point on day 1(T1),day 7(T2),day 14(T3),1 month(T4),3 months(T5),and 1 year(T6)were collected and recorded for both groups.The differences in treatment effect,complications and recurrence between the 2 groups were compared,and the related influencing factors were analyzed. Results:The differences of general information,preoperative pain scores,foramen ovale morphology,foramen ovale area,T1 to T3 pain scores between the 2 groups were not statistically different(all P>0.05).The balloon filling volume in the PBC group was smaller than that in the RT+PBC group,the pain scores at T4 to T6 and pain recurrence were better than those in the RT+PBC group(all P<0.05).Pain recurrence was positively correlated with pain scores of T2 to T6(r=0.306,0.482,0.831,0.876,0.887,respectively;all P<0.01). Conclusion:The choice of PBC for the first intervention in PTN patients is superior to the choice of PBC after pain recurrence after RT treatment in terms of treatment outcome and pain recurrence.
摘要
Trigeminal neuralgia is a manifestation of orofacial neuropathic pain disorder,always deemed to be an insurmountable peak in the field of pain research and treatment.The pain is recurrent,abrupt in onset and termination similar to an electric shock or described as shooting.A poor quality of life has been attributed to trigeminal neuralgia,as the paroxysms of pain may be triggered by innocuous stimuli on the face or inside the oral cavity,such as talking,washing face,chewing and brushing teeth in daily life.The pathogenesis of trigeminal neuralgia has not been fully elucidated,although the microvascular compression in the trigeminal root entry zone is generally considered to be involved in the emergence and progression of the pain disorder.In addition,orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve might be secondary to peripheral nerve injury.Based on current hypotheses regarding the potential causes,a variety of animal models have been designed to simulate the pathogenesis of trigeminal neuralgia,including models of compression applied to the trigeminal nerve root or trigeminal ganglion,chronic peripheral nerve injury,peripheral inflammatory pain and center-induced pain.However,it has not yet been possible to determine which model can be perfectly employed to explain the mechanisms.The selection of appropriate animal models is of great significance for the study of trigeminal neuralgia.Therefore,it is necessary to discuss the characteristics of the animal models in terms of animal strains,materials,operation methods and behavior observation,in order to gain insight into the research progress in animal models of trigeminal neuralgia.In the future,animal models that closely resemble the features of human trigeminal neuralgia pathogenesis need to be developed,with the aim of making valuable contributions to the relevant basic and translational medical research.
摘要
Secondary trigeminal neuralgia after brainstem infarction is rare and rarely reported.A patient with secondary trigeminal neuralgia after brainstem infarction was admitted to the Department of Neurosurgery,Xiangya Hospital,Central South University.The patient was a 44 years old male who underwent motor cortex stimulation treatment after admission.The effect was satisfactory in the first week after surgery,but the effect was not satisfactory after one week.This disease is relatively rare and the choice of clinical treatment still requires long-term observation.
摘要
Objective To investigate the clinical efficacy of CT-guided pulsed radiofrequency combined with continuous nerve block in the treatment of refractory postherpetic neuralgia(PHN).Methods A total of 208 patients with refractory PHN,who were admitted to the Hengshui Municipal People's Hospital of China between January 2021 and January 2023,were selected as the subjects of study.Using random number table method,the patients were divided into combination group and control group,with 104 patients in each group.The patients of control group received CT-guided pulsed radiofrequency therapy,and the patients of combination group received additional continuous nerve block therapy on the basis of the treatment of control group.The pain degree at different time point,clinical effective rate,number of analgesia remedy times,quality of sleep,and the levels of serum high mobility group box 1(HMGB1),interleukin-1 β(IL-1β)and interleukin-10(IL-10)were compared between the two groups.Results During the follow-up period,4 patients were lost in touch.Finally,103 patients were included in the combination group and 101 patients were included in the control group.The total treatment response rate in the combination group was 89.32％,which was significantly higher than 78.22％in the control group(P＜0.05).There were statistically significant differences in visual analogue scale(V AS)scores and Athens insomnia scale(AIS)scores including the time effect,inter-group effect and time-group interaction effect,between the two groups(P＜0.05).The postoperative one-week,2-week,4-week VAS scores and AIS scores in the combination group were remarkably lower than those in the control group(P＜0.05).The number of analgesia remedy times in the combination group was smaller than that in the control group,and the used dosage of tramadol in the combination group was lower than that in the control group(P＜0.05).Four weeks after treatment,the serum levels of HMGB1,IL-1β and IL-10 in the combination group were lower than those in the control group(P＜0.05).Conclusion For the treatment of refractory PHN,CT-guided pulsed radiofrequency combined with continuous nerve block can effectively alleviate neural inflammatory damage,and improve pain symptoms and sleep quality,besides,its analgesic effect and clinical efficacy are superior to CT-guided pulsed radiofrequency alone.(J Intervent Radiol,2024,33:264-268)
摘要
Objective·To investigate the efficacy and safety of hypertonic dextrose prolotherapy(DPT)in the treatment of postherpetic neuralgia.Methods·Seventy-eight patients with postherpetic neuralgia who visited the Department of Pain of The Affiliated Hospital of Xuzhou Medical University from June 2019 to December 2022 were selected.The patients were randomly assigned to a control group and a research group in a 1∶1 ratio,with 39 patients in each group.The control group was treated with traditional analgesic solution,while the research group was treated with traditional analgesic solution combined with DPT.Visual analog scale(VAS)was used to evaluate the patients'pain level before and after treatment,flow cytometry was used to measure the patients'T-cell subsets,and enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of C-reactive protein(CRP),interleukin-6(IL-6),and IL-10 cytokines.The VAS scores were compared between the two groups of patients before and at 1,2,4,8,and 12 weeks after treatment.CD4+/CD8+,CRP,IL-6,IL-10 levels,and the incidence of adverse reactions before and 2 weeks after treatment were compared between the two groups.Results·There was no statistically significant difference in sex ratio,age,and disease duration between the two groups of patients.The VAS scores of the two groups of patients at 1,2,4,8,and 12 weeks after treatment were significantly lower than those before treatment,and the differences were statistically significant(all P<0.05).The VAS scores of the research group at 1,2,4,8,and 12 weeks after treatment were significantly lower than those of the control group(all P<0.05).There was no statistically significant difference in basal CD4+/CD8+,CRP,IL-6 and IL-10 levels between the two groups of patients.IL-6 and CRP levels in the research group were significantly lower after treatment than those in the control group,and the differences were statistically significant(all P=0.000).CD4+/CD8+ and IL-10 levels were significantly higher in the research group than those in the control group after treatment,and the difference was statistically significant(all P=0.000).No adverse reactions such as local nerve damage,epidural hematoma,infection,pneumothorax or allergy occurred in both groups of patients during the treatment.Conclusion·DPT can significantly reduce the pain of PHN patients,improve patients'T lymphocyte subpopulations and cytokine expression,and can be safely applied to the clinic.
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Objective Exploring the efficacy and safety of botulinum toxin type A(BTX-A)combined with pulsed radiofrequency(PRF)in the treatment of postherpetic neuralgia(PHN).Methods A total of 80 patients with PHN were collected.They were randomly divided into experimental group(Group B)and control group(Group C),Group B was treated with BTX-A intradermal injection combined with PRF,and Group C was treated with lidocaine intradermal injection combined with PRF.Numeric pain score(NRS),Simplified McGill Pain Questionnaire(SF-MPQ)and Sleep Quality Score(QS)were used to assess the patients'pain level and sleep quality preoperatively,1,3,and 7 days postoperatively,and 1,2,and 3 months postoperatively.The patients'postoperative adverse reac-tions were collected.Interleukin-1β(IL-1β)and calcitonin gene-related peptide(CGRP)levels in patients'serum were measured preoperatively and 3 days postoperatively.Results The NRS scores,SF-MPQ scores,and QS scores of group B and group C were significantly lower at all postoperative time points compared to preoperative ones(P<0.05).The NRS and SF-MPQ score were significantly lower in group B at 1,2,and 3 months postoperatively compared with group C(P<0.05);and group B had significantly lower QS scores at 2 and 3 months postoperatively(P<0.05).The effective rate of pain relief at 3 months postoperatively in group B(90%)was statistically signifi-cant(P<0.05)compared with group C(56.7%).No serious adverse reactions occurred in either group.The levels of IL-1β and CGRP in serum of patients in both groups were significantly decreased at 3 days after surgery compared with the preoperative period,and the degree of decrease of IL-1β and CGRP in group B was more significant than that in group C(P<0.05).Conclusion BTX-A combined with PRF treatment for PHN can effectively reduce its pain level,improve the quality of sleep,and is safe.
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Objective To investigate the impact of quercetin(Que)on postherpetic neuralgia(PHN)and chemokine ligand 3(CCL3,namely MIP-1α)/C-C chemokine receptor 1(CCR1)/C-C chemokine receptor 5(CCR5)signaling pathway in rats.Methods Sixty rats were divided into the control group(Con),the PHN group(model group),the L-Que(30 mg/kg)group,the M-Que(60 mg/kg)group,the H-Que(120 mg/kg)group and the H-Que+pathway activator MIP-1α(120 mg/kg Que+0.4 mg/kg recombinant MIP-1α)group.The mechanical paw withdrawal threshold(PWT)and thermal pain threshold(TWL)of rats were detected in each group.The kit was used to detect adenosine,Adenine ribonucleotide(AMP),adenosine diphosphate(ADP)and tumor necrosis factor in spinal dorsal horn samples-α(TNF-α),and interleukin-1 β(IL-1 β)levels in spinal dorsal horn samples.HE staining was applied to observe the pathological sections of spinal dorsal horn.Immunofluorescence staining was used to detect the activation of microglia in spinal dorsal horn.Western blot assay was applied to detect MIP-1α/CCR1/CCR5 signaling pathway protein expression.Results In the PHN group,the dorsal horn of the spinal cord was ruptured,the arrangement of nerve bundles was disordered,and inflammatory cell infiltration,edema,and slight atrophy of neurons appeared.Compared with the Con group,the PWT value,adenosine,AMP and ADP levels were obviously decreased in the PHN group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1-positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).After treatment with Que,the disordered arrangement of nerve bundles was improved,the infiltration of inflammatory cells was reduced,and the phenomenon of neuronal atrophy disappeared.Compared with the PHN group,the PWT value,adenosine,AMP and ADP levels were obviously increased in the L-Que group,the M-Que group and the H-Que group(P＜0.05).TWL value,TNF-αand IL-1β levels,the number of Iba1-positive microglia,and MIP-1α,CCR1 and CCR5 protein levels were obviously decreased(P＜0.05).The effect of Que was dose dependent.Compared with the H-Que group,PWT value,adenosine,AMP and ADP levels were obviously decreased in the H-Que+MIP-1α group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1 positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).Conclusion Que may reduce the inflammatory response in rats by inhibiting the MIP-1α/CCR1/CCR5 signaling pathway,thereby reducing PHN.
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Objective To evaluate the role of autophagy in the treatment of neuropathic pain(NP)with hydrogen-rich saline.Methods Forty adult male Sprague-Dawley rats with successful intubation were randomly divided into 5 groups(n= 8)using a random number table:the sham operation group(group S),the neuropathic pain group(group C),the hydrogen-rich saline group(group H),the autophagy inhibitor group(group M)and the hydrogen-rich saline + autophagy inhibitor group(group HM).There were 8 rats in each group.The NP model was established by chronic constriction of the sciatic nerve(CCI)in rats.The autophagy inhibitor 3-methyladenine(3-MA)was intraperitoneally injected with 30μg/kg in the group M and the group HM.The hydrogen-rich saline(0.6 mmol/L)was intraperitoneally injected with 10 mL/kg in the group H and the group HM.The other groups were intraperitoneally injected with the same amount of normal saline twice a day for 7 consecutive days.Paw withdrawal threshold to mechanical stimulation(MWT)and paw withdrawal latency to thermal stimulation(TWL)were measured at 1 day before and 1,3,5,7 and 14 days after modeling(T0-T5).After the last measurement of pain threshold,the L4-L6 segment of spinal cord was removed for determination of the expression of autophagy-related proteins microtubule-associated protein light chain 3(LC3)Ⅱ,Beclin-1 and p62 proteins by Western blot assay.The expression levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in spinal cord tissue were detected.Results Compared with the group S,MWT and TWL were decreased in the group C at T2-5,the expression levels of LC3 Ⅱ,Beclin-1 and p62 were increased,SOD activity was decreased,and MDA content was increased at T5(P＜0.05).Compared with the group C,MWT and TWL were increased in the group H at T2-5,LC3 Ⅱ and Beclin-1 protein expression levels were increased,p62 protein expression levels were decreased,SOD activity was increased,and MDA content was decreased at T5(P＜0.05).MWT and TWL were decreased in the group M at T2-5,LC3 Ⅱ and Beclin-1 protein expression levels were decreased,p62 protein expression levels were increased,SOD activity was decreased,and MDA content was increased at T5(P＜0.05).Compared with the group M,MWT and TWL were increased in the group HM at T2-5,LC3 Ⅱ and Beclin-1 protein expression levels were increased,p62 protein expression levels were decreased,SOD activity was increased,and MDA content was decreased at T5(P＜0.05).Conclusion Hydrogen-rich saline can alleviate neuropathic pain and inhibit oxidative stress in spinal cord in rats,and the mechanism may be related to the increase of autophagy.
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Objective:To evaluate the effect of electroacupuncture on P2X4R-p38 mitogen-activated protein kinase (p38 MAPK)-brain-derived neurotrophic factor (BDNF) signaling pathway in trigeminal ganglion of rats with trigeminal neuralgia.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), and electroacupuncture group (E group). The model was developed by chronic constriction of the infraorbital nerve in anesthetized animals. The infraorbital nerve was only exposed without ligation in group S. Rats received electroacupuncture stimulation at the Baihui and Xiaguan acupoints on the affected side for 20 min after developing the model, with a frequency of 80 Hz, twice a day, for 14 consecutive days in E group. Facial mechanical pain threshold (FMT) was measured at 1 day before developing the model and 3, 7, 14, 21 and 28 days after developing the model. The rats were sacrificed after the last behavioral testing, and the trigeminal ganglia were taken for examination of histopathological changes of trigeminal ganglion (by HE staining) and for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the FMT was significantly decreased at each time point after developing the model, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased ( P<0.05), the pathological changes of the trigeminal ganglion were obvious in group TN. Compared with group TN, the FMT was significantly increased at each time point after developing the model, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased ( P<0.05), and the pathological changes of the trigeminal ganglion were significantly attenuated in group E. Conclusions:The mechanism by which electroacupuncture alleviates trigeminal neuralgia may be related to inhibiting the activity of P2X4R-p38MAPK-BDNF signaling pathway and reducing neuroinflammation in rats.
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Objective:To evaluate the effect of gastrogin on AMP-activated protein kinase (AMPK)/transient receptor potential anchor protein 1 (TRPA1) signaling pathway in rats with neuropathic pain.Methods:Thirty-six SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-230 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation+ normal saline group (SHAM group), neuropathic pain+ normal saline group (NP group), and neuropathic pain+ gastrogin group (GAS group). Neuropathic pain was induced by chronic constrictive injury to sciatic nerve under 2% isoflurane anaesthesia. The sciatic nerve was only exposed but not ligated in SHAM group. Gastrogin 100 mg/kg was intraperitoneally injected for 14 consecutive days after developing the model in GAS group, while the equal volume of normal saline was given instead in SHAM and NP groups. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model (T 0) and 1, 3, 5, 7, 10 and 14 days after developing the model (T 1-6). The rats were anesthetized and sacrificed following the measurement of pain thresholds at T 4 and T 6. The lumbar segment (L 4-6) of the spinal cord was removed for determination of TRPA1 mRNA expression (by quantitative real-time polymerase chain reaction), expression of TRPA1, AMPK and p-AMPK (by Western blot), expression of TRPA1 (by immunofluorescence staining) and expression of tumor necrosis-alpha(TNF-α), interleukin-1beta(IL-1β) and c-fos (by immunohistochemistry). Results:Compared with SHAM group, MWT and TWL were significantly decreased at T 1-6, the expression of TRPA1 mRNA, TRPA1, TNF-α, IL-1β and c-fos was up-regulated, the expression of p-AMPK was down-regulated ( P<0.05), and no significant change was found in AMPK expression in NP group ( P>0.05). Compared with NP group, MWT at T 3-6 and TWL at T 2-6 were significantly increased, the expression of TRPA1 mRNA, TRPA1, TNF-α, IL-1β and c-fos was down-regulated, and p-AMPK expression was up-regulated ( P<0.05), and no significant change was found in AMPK expression in GAS group ( P>0.05). Conclusions:The mechanism by which gastrogin reduces neuropathic pain may be related to modulating the expression of the AMPK/TRPA1 signaling pathway in rats.
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Objective:To investigate the clinical efficacy of individualised microvascular decompression (MVD) for trigeminal neuralgia (TN), so as to provide individualised treatment strategies and new thoughts for treatment.Methods:Clinical data of 46 patients who had TN and treated in the Department of Neurosurgery at the First Affiliated Hospital of Anhui Medical University from January 2021 to September 2023 were retrospectively studied. The study consisted of 19 males and 27 females, with an average age of morbidity at (58.3 ± 9.0) years old. Preoperative pain ratings and surgical outcomes were evaluated using the Barrow Neurological Institute (BNI) pain rating scale, and of which 27 patients were rated at BNI grade IV and 19 at grade V before surgery. A posterior trans-sigmoid sinus approach was applied in surgery on all patients, which could be performed in various ways depending on the vascular conditions identified during surgery. Ten patients were treated with microsurgery, 12 with endoscopic surgery and 24 with combined endoscopic surgery and microsurgery. After having identified the responsible vessel(s), a vascular decompression for the affected trigeminal nerve was performed and the nerve decompression was achieved by a polyester pad. Long-term postoperative follow-ups were conducted via telephone interviews or outpatient visits.Results:A total of 46 patients received the microvascular decompression surgery. Among them, 43 cases (93.5%) achieved immediate and complete pain relief of BNI grade I after surgery, and 3 cases (6.5%) achieved partial pain relief of BNI grade Ⅱ. Four patients developed facial numbness and sensory reduction, 2 developed facial paralysis (of House-Brackmann grade Ⅱ of 1 patient and grade Ⅲ of the other), 8 developed pneumocephalus, 4 developed postoperative fever, and 2 developed subcutaneous effusion. After treatment, the pneumocephalus and fever were cured, subcutaneous effusion was disappeared in 1 patient, but remained in the other. The mean follow-up period for the 46 patients was 16.2 (1-33) months. During the follow-up, 2 of the 3 patients of BNI grade Ⅱ immediately after surgery had complete remission to BNI grade Ⅰ and the other had recurrence and aggravation at BNI grade Ⅳ.Conclusion:The complexity of the responsible vessels is one of the important factors to be considered in the microvascular decompression strategy for trigeminal neuralgia. An individualised surgical plan according to a specific vascular condition identified in the surgery, is a best possible or worthiness surgical strategy in the treatment for a TN.
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Objective @#To construct a rat model of trigeminal neuralgia ( TN) to explore the expression of high mobility group box-1 (HMGB1) in the trigeminal ganglion (TG) and the possible mechanism of HMGB1 effect on pain . @*Methods @#TN model was constructed by infraorbital nerve constriction and divided into operation group (CCI group) and Sham group , and the success of the model construction was determined through mechanical pain thresh old assessment. Real time fluorescence quantitative PCR ( RT-qPCR) and Western blot were used to detect high mobility group protein B1 (HMGB1) , Toll receptor 4 (TLR4) , and Nuclear Factor Kappa B(NF-κB) mRNA and protein expression in the ipsilateral trigeminal ganglion (TG) of the Sham and CCI rats . 50 mg/kg HMGB1 inhibi tor glycyrrhizin (GL) was inj ected intraperitoneally every day for two week s , and normal saline (NS) was used as control . The patients were divided into CCI group , CCI + NS group and CCI + GL group . HMGB1 , TLR4 , and NF- κB mRNA and protein expression in the ipsilateral trigeminal ganglion (TG) were detected by RT-qPCR and West ern blot in CCI group , CCI + NS group , and CCI + GL group . @*Results @#The mechanical threshold on the operated side of the rat continued to decrease (P < 0.05) , and mechanical pain threshold identification model was success fully constructed . After chronic compressive injury to the infraorbital nerve in rats , HMGB1 , TLR4 , and NF-κB mRNA and protein expression in TG on the operated side increased ( P < 0.05) ; After administration of HMGB1 inhibitor Glcyrrhizin , HMGB1 , TLR4 , NF-κB showed a decrease (P < 0.05) .@*Conclusion @#HMGB1 is associat ed with TN , and HMGB1 may be involved in the pathogenesis of TN through TLR4/NF-κB signaling pathway.
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Objective:To analyze the influencing factors for efficacy of microvascular decompression (MVD) in primary trigeminal neuralgia (PTN).Methods:A retrospective study was performed. Clinical data of 178 patients with PTN underwent MVD at Department of Neurosurgery, Affiliated Hospital Affiliated to Nantong University from January 2018 to April 2022 were collected. Efficacy was evaluated according to Brisman's criteria. Differences of MVD efficacy in patients with different clinical characteristics or different neurovascular characteristics were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for MVD efficacy.Results:All patients were followed up for about 2 years; at the last follow-up, 164 patients (92.13%) had good postoperative efficacy (130 were cured, 28 were obvious improved, and 6 were improved); 14 patients (7.87%) had poor postoperative efficacy (10 were ineffective and 4 were relapsed). No significant difference in surgical efficacy was noted among patients with different gender, age, left/right lateral pain, disease courses or pain degrees ( P>0.05). Patients with different contact degrees between the trigeminal nerve and blood vessels, different distances between the trigeminal nerve and blood vessels, and different curvature degrees of the posterior trigeminal nerve had significantly different surgical efficacy ( P<0.05). Multivariate Logistic regression indicated that contact degrees between the trigeminal nerve and blood vessels ( OR=0.233, 95% CI: 0.080-0.675, P=0.007), distances between the trigeminal nerve and blood vessels ( OR=6.991, 95% CI: 3.261-14.984, P=0.000), and curvature degrees of the posterior trigeminal nerve ( OR=0.351, 95% CI: 0.158-0.776, P<0.001) were independent influencing factors for postoperative outcomes. Conclusion:The postoperative efficacy is good in patients with slight contact between the trigeminal nerve and blood vessels, with distance between the trigeminal nerve and blood vessels greater than 1×time median width of the trigeminal nerve (WTN), or with hypotenuse height of the arced trigeminal nerve less than 1/2 WTN.
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Objective @#To evaluate the therapeutic effect of CT/MRI image fusion and usual CT guided percutaneous radiofrequency thermocoagulation of trigeminal semilunar ganglion . @*Methods @#The medical information of 88 patients diagnosed with primary trigeminal neuralgia were assembled . In accordance with different imaging guidance means , they were equally divided into the control group ( trigeminal semilunar ganglion radiofrequency thermo coagulation with CT guidance ) and the fusion group ( trigeminal semilunar ganglion radiofrequency thermocoagula tion with assistance of CT/MRI image fusion technology) at random. The puncture time , intraoperative discomfort rate , preoperative , intraoperative and postoperative visual analogue scale (VAS) score , Barrow neurological insti tute (BNI) pain score and postoperative complication rate were contrasted . @*Results @#The puncture operation time of the fusion group was shorter than that of the control group (P < 0 05) ; the intraoperative and postoperative VAS and BNI scores , occurrence rate of intraoperative discomfort and postoperative complications in the fusion group were lower than those in the control group (P < 0.05) .@*Conclusion @#In respect of improving therapeutic effect and diminishing intraoperative discomfort and postoperative complications , CT/MRI image fusion technique is superior to CT guidance .
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ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg-1·d-1）， high-dose Lutongning group （2.70 g·kg-1·d-1）， and low-dose Lutongning group （1.35 g·kg-1·d-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.