Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte formation, synovial inflammation, and meniscal damage. Although the etiology of OA is multifactorial, pro-inflammatory processes appear to play a key role in disease pathogenesis. Previous studies indicate that electroacupuncture (EA) exerts chondroprotective, anti-inflammatory, and analgesic effects in preclinical models of OA, but the mechanisms underlying these potential therapeutic benefits remain incompletely defined. This study aimed to investigate the effects of EA on OA development in a rat model, as well as to explore associated molecular mechanisms modulated by EA treatment. Forty rats were divided into OA, EA, antagomiR-214, and control groups. Following intra-articular injection of monosodium iodoacetate to induce OA, EA and antagomiR-214 groups received daily EA stimulation at acupoints around the knee joint for 21 days. Functional pain behaviors and chondrocyte apoptosis were assessed as outcome measures. The expression of microRNA-214 (miR-214) and its downstream targets involved in apoptosis and nociception, BAX and TRPV4, were examined. Results demonstrated that EA treatment upregulated miR-214 expression in OA knee cartilage. By suppressing pro-apoptotic BAX and pro-nociceptive TRPV4, this EA-induced miR-214 upregulation ameliorated articular pain and prevented chondrocyte apoptosis. These findings suggested that miR-214 plays a key role mediating EA's therapeutic effects in OA pathophysiology, and represents a promising OA treatment target for modulation by acupuncture. (OA cartilage remodeling formation inflammation damage multifactorial proinflammatory pro inflammatory pathogenesis (EA chondroprotective antiinflammatory, antiinflammatory anti inflammatory, anti-inflammatory defined model antagomiR214, antagomiR214 antagomiR 214, 214 intraarticular intra antagomiR-21 2 days measures microRNA214 microRNA microRNA-21 miR214 miR (miR-214 nociception TRPV4 TRPV examined miR-21 proapoptotic apoptotic pronociceptive nociceptive EAinduced induced EAs s pathophysiology acupuncture antagomiR21 antagomiR-2 microRNA21 microRNA-2 miR21 (miR-21 miR-2 antagomiR2 antagomiR- microRNA2 microRNA- miR2 (miR-2 miR- (miR- (miR

Abstract Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.

ABSTRACT Background: The emergence of the Nerve Growth Factor (NGF) has promoted the development of neuroprotective therapy; however, it has little effect on cerebral ischemia because of its poor Blood-Brain Barrier (BBB) permeability. Specific Mode Electroacupuncture Stimulation (SMES) can open BBB safely and effectively; however, it has shown inconclusive clinical effects and indirect clinical evidence in the recovery phase. Hence, the authors conducted a multicentre, randomized, placebo-controlled, assessor-blinded clinical trial to assess the effectiveness and safety of SMES combined with NGF treatment used during ischaemic stroke recovery. Methods: A total of 288 stroke patients from three hospitals will be recruited and randomly allocated to four groups: acupuncture + placebo, acupuncture + NGF, SMES + placebo, and SMES + NGF, in a 1:1:1:1 ratio. Assessment data will be collected at baseline, 2-weeks, and 4-weeks during the treatment period, as well as at the 4-week and 8-week follow-up after treatment completion. The primary outcome measure will be the basic cure rate. The secondary outcome measures include the simplified Modified Barthel Index, Timed Up and Go Test, Fugl-Meyer Assessment of Motor Function Score, Tinetti Performance Oriented Mobility Assessment, Montreal Cognitive Assessment, and Loewenstein Occupational Therapy Cognitive Assessment. Moreover, resting-state functional magnetic resonance imaging and Functional near-infrared spectroscopy can detect changes in cerebral blood flow and brain function and investigate the relationship between the clinical efficacy and mechanism of the prescribed interventions. Conclusion: This study will provide clinical evidence for the efficacy and safety of SMES combined with NGF in the treatment of stroke patients. Background (NGF therapy however BloodBrain Blood Brain (BBB permeability (SMES effectively phase Hence multicentre randomized placebocontrolled, placebocontrolled placebo controlled, controlled placebo-controlled assessorblinded assessor blinded Methods 28 groups 1111 1 1:1:1: ratio baseline 2weeks, 2weeks weeks 2 weeks, 2-weeks 4weeks 4 period 4week week 8week 8 followup follow up completion rate Index Test FuglMeyer Fugl Meyer Score Moreover restingstate resting state nearinfrared near infrared interventions Conclusion 111 1:1:1 11 1:1: 1:1 1:

Abstract Objective In the context of postoperative anal pain, understanding the intricate mechanisms and effective interventions is paramount. This study investigates the role of Muscarinic Acetylcholine Receptors (mAChRs) and the IP3-Ca2+-CaM signaling pathway in a rat model of postoperative anal pain, exploring the potential analgesic effects of electroacupuncture. Methods Comprehensive approaches involving mechanical sensitivity assays, Western blotting, immunohistochemistry, and intracellular calcium concentration measurement were used. Results The authors found elevated mAChRs expression in the postoperative pain model. Antagonizing mAChRs reduced pain sensitivity and attenuated the IP3-Ca2+-CaM pathway. Remarkably, electroacupuncture treatment further mitigated pain, potentially by suppressing this signaling cascade. Interpretation These findings reveal a novel connection between mAChRs and the IP3-Ca2+-CaM pathway in postoperative anal pain and suggest electroacupuncture as a promising avenue for pain relief through these mechanisms, offering insights into innovative strategies for postoperative pain management. paramount (mAChRs IP3Ca2+CaM IP3Ca2CaM IPCaCaM IP3 Ca2+ CaM Ca2 IP Ca assays blotting immunohistochemistry used Remarkably cascade management IP3Ca2 IPCa IP3Ca

Objective: Depression is a major public health problem. Many complementary and alternative medicine (CAM) interventions have been suggested as potential treatments. This umbrella review aimed to assess the efficacy and safety of CAM interventions for treating depression. Methods: We comprehensively searched for relevant systematic reviews and meta-analyses in the MEDLINE (via PubMed), EMBASE, Web of Science, and Cochrane Library databases. We assessed effectiveness (based on efficacy and changes in depression assessment scale scores) and safety (based on adverse events). Results: A total of 22 eligible articles were included. Yueju antidepressant and electro-acupuncture (EA) improved depression symptoms better than conventional antidepressants. In addition, omega-3 fatty acids (n-3PUFAs), exercise, manual acupuncture (MA), Hypericum mono-preparations, relaxation, and vitamin D showed superior efficacy to placebo and controls. Guipi decotion (GPD) as adjunctive therapy has higher efficacy than conventional antidepressants, and MA and Yueju have a better safety profile than conventional antidepressants. Conclusion: 10 CAMs can effectively improve the condition of patients with clinical depression. Objective problem (CAM treatments Methods metaanalyses meta analyses via PubMed, PubMed , PubMed) EMBASE Science databases based scores events. events . events) Results 2 included electroacupuncture electro EA (EA antidepressants addition omega3 omega 3 omega- n3PUFAs, n3PUFAs nPUFAs n 3PUFAs PUFAs (n-3PUFAs) exercise MA, (MA) monopreparations, monopreparations mono preparations, preparations mono-preparations relaxation controls GPD (GPD Conclusion 1 (n-3PUFAs (MA

RESUMO Introdução: A lesão meniscal é um acometimento comum que pode gerar incapacitação por dor e falha proprioceptiva, exigindo atenção imediata. Terapias combinadas envolvem abordagens avançadas com o objetivo de acelerar a reabilitação nos atletas, e a eletroacupuntura apresenta benefícios terapêuticos, embora ainda não possua evidencias de sua combinação com a terapia esportiva. Objetivo: Analisar o desempenho da reabilitação esportiva em atletas com lesão meniscal utilizando eletroacupuntura combinada à terapia esportiva. Métodos: A intervenção no grupo controle baseou-se no trabalho tradicional de amplitude de movimento, força muscular, treinamento proprioceptivo e outros tipos de terapias de exercício enquanto que ao grupo experimental foi adicionado um protocolo de eletro-acupuntura de 30 minutos de duração, 3 vezes por semana durante 4 semanas consecutivas. Os dados de substituição (sexo, idade, curso de doença, localização) são basicamente os mesmos. Antes do tratamento, a atividade articular, a força muscular, o escore total da escala articular do questionário LYSHOLM e outros índices de observação foram medidos na 6ª e 12ª semana do tratamento. O método estatístico não paramétrico e teste-T foram utilizados para analisar as alterações de cada índice antes e depois do tratamento. Após 12 semanas de tratamento, a diferença entre o grupo experimental e a combinação antes do tratamento foi significativa. Resultados: O efeito de tratamento do grupo experimental foi significativamente melhor do que o grupo controle. Conclusão: O efeito de reabilitação esportiva de atletas com lesão meniscal baseada em eletroacupuntura combinada à terapia esportiva demonstrou alto valor de aplicação resolutiva, indicada como alternativa para o tratamento não cirúrgico em lesões no menisco do joelho. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Introduction: Meniscal injury is a common condition that can lead to disability due to pain and proprioceptive failure, requiring immediate attention. Combination therapies involve advanced approaches aiming to accelerate rehabilitation in athletes, and electroacupuncture presents therapeutic benefits, although there is still no evidence of its combination with sports therapy. Objective: This paper analyzes the performance of sports rehabilitation in athletes with meniscal lesions using electroacupuncture combined with sports therapy. Methods: The intervention in the control group was based on a traditional range of motion work, muscle strength, proprioceptive training, and other exercise therapies, while the experimental group received a 30 min electro-acupuncture protocol three times a week for four consecutive weeks. The surrogate data (gender, age, disease course, location) are the same. Before treatment, joint activity, muscle strength, total joint scale score of the LYSHOLM questionnaire, and other observational indices were measured during the 6th and 12th week of treatment. The non-parametric statistical method and T-test were used to analyze the changes of each index before and after treatment. After 12 weeks of treatment, the difference between the experimental group and the combination before treatment was significant. Results: The treatment effect of the experimental group was significantly better than the control group. Conclusion: The effect of sports rehabilitation of athletes with meniscus injury based on electroacupuncture combined with sports therapy showed high resolutive application value, indicating an alternative for non-surgical treatment in knee meniscus injuries. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

Resumen Introducción: La lesión meniscal es una lesión común que puede causar incapacidad por dolor y fallo propioceptivo, requiriendo atención inmediata. Las terapias combinadas implican enfoques avanzados con el objetivo de acelerar la rehabilitación en los deportistas, y la electroacupuntura presenta beneficios terapéuticos, aunque todavía no hay pruebas de su combinación con la terapia deportiva. Objetivo: Analizar el rendimiento de la rehabilitación deportiva en atletas con lesión meniscal utilizando electroacupuntura combinada con la terapia deportiva. Métodos: La intervención en el grupo de control se basó en el trabajo tradicional de amplitud de movimiento, fuerza muscular, entrenamiento propioceptivo y otros tipos de terapias de ejercicio, mientras que al grupo experimental se le añadió un protocolo de electroacupuntura de 30 minutos de duración, 3 veces a la semana durante 4 semanas consecutivas. Los datos sustitutivos (sexo, edad, evolución de la enfermedad, localización) son básicamente los mismos. Antes del tratamiento, se midieron la actividad articular, la fuerza muscular, la puntuación total de la escala articular del cuestionario LYSHOLM y otros índices de observación en la 6ª y 12ª semana de tratamiento. Se utilizó el método estadístico no paramétrico y la prueba T para analizar los cambios de cada índice antes y después del tratamiento. Tras 12 semanas de tratamiento, la diferencia entre el grupo experimental y la combinación antes del tratamiento era significativa. Resultados: El efecto del tratamiento del grupo experimental fue significativamente mejor que el del grupo de control. Conclusión: El efecto de la rehabilitación deportiva de atletas con lesión de menisco basada en la electroacupuntura combinada con la terapia deportiva mostró un alto valor de aplicación resolutiva, indicada como alternativa de tratamiento no quirúrgico en las lesiones de menisco de rodilla. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Abstract Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic spine remodeling can relieve neuropathic pain. Electroacupuncture (EA) has a beneficial effect on the treatment of neuropathic pain, but the specific mechanism remains unclear. Evidence has shown that slit-robo GTPase activating protein 3 (srGAP3) and Rho GTPase (Rac1) play very important roles in dendritic spine remodeling. Here, we used srGAP3 siRNA and Rac1 activator CN04 to confirm the relationship between SrGAP3 and Rac1 and their roles in improving neuropathic pain with EA. Spinal nerve ligation (SNL) was used as the experimental model, and thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), Western blotting, immunohistochemistry and Golgi-Cox staining were used to examine changes in behavioral performance, protein expression and dendritic spines. More dendritic spines and higher expression levels of srGAP3 were found in the initial phase of neuropathic pain. During the maintenance phase, dendritic spines were more mature, which was consistent with lower expression levels of srGAP3 and higher expression levels of Rac1-GTP. EA during the maintenance phase reduced the density and maturity of dendritic spines of rats with SNL, increased the levels of srGAP3 and reduced the levels of Rac1-GTP, while srGAP3 siRNA and CN04 reversed the therapeutic effects of EA. These results suggest that dendritic spines have different manifestations in different stages of neuropathic pain and that EA may inhibit the abnormal dendritic spine remodeling by regulating the srGAP3/Rac1 signaling pathway to alleviate neuropathic pain.

ABSTRACT Objective: To analyze the response of post-surgical pain to the application of electroacupuncture and moxibustion using the IKDC scale. Methods: Quasi-experimental study in the integral clinic of the Universidad Estatal del Valle de Toluca, the treatment consisted of the consented application of ten sessions of electroacupuncture and moxibustion distributed in two weekly sessions of 30 minutes for the monitoring of postoperative pain in anterior cruciate ligament plasty. Results: 100 % pain reduction (VAS 0/10) was obtained from the sixth session (21 days), 100 % recovery of the surgical wounds was observed, edema was reduced to 75 % (Godet sign 1+/4+) and mobility was increased to 59% IKDC (47.4/80 total points). Conclusions: The effectiveness of therapy with electroacupuncture (1) and moxibustion (2,3) in the treatment of post-surgical pain was evidenced by means of the IKDC (4) scale at the end of the ten sessions, in addition to accelerated healing, decreased edema and increased joint mobility in less time, being a therapeutic option in analgesia and recovery from surgical procedures as long as it is practiced according to the scientific, clinical bases.

RESUMEN Objetivo: Analizar la respuesta del dolor postquirúrgico ante la aplicación de electroacupuntura y moxibustión mediante la escala IKDC. Método: Estudio cuasiexperimental en la clínica integral de la Universidad Estatal del Valle de Toluca. el tratamiento consistió en la aplicación consentida de diez sesiones de electroacupuntura y moxibustión distribuidas en dos sesiones semanales de 30 minutos para el monitoreo del dolor postquirúrgico en plastia del ligamento cruzado anterior. Resultados: Se obtuvo disminución del dolor al 100 % (EVA 0/10) a partir de la sexta sesión (21 días) observó recuperación de las heridas quirúrgicas al 100 %, disminución del edema al 75 % (signo Godet 1+/4+) y aumento de la movilidad al 59 % IKDC (47,4/80 puntos totales). Conclusiones: Se evidenció la efectividad de la terapia con electroacupuntura (1) y moxibustión (2,3) en el tratamiento del dolor postquirúrgico por medio de la escala IKDC (4) al concluir las diez sesiones, además de cicatrización acelerada, disminución del edema y aumento en la movilidad articular en menor tiempo, siendo una opción terapéutica en la analgesia y recuperación de procedimientos quirúrgicos siempre que se practique conforme a las bases científicas, clínicas.

ABSTRACT Introduction: The temporomandibular disorders constitute a painful condition that affects the mastication muscles, the temporomandibular joint, as well as several anatomical structures of the stomatognathic system. Objective: To evaluate the effectiveness of electroacupuncture in patients with syndrome of miofacial pain associated with temporomandibular joint dysfunction. Methods: A quasi-experiment study of therapeutic intervention in 80 patients assisted in Dr. Juan Bruno Zayas Alfonso Teaching General Hospital from Santiago de Cuba, was carried out from November, 2018 to the same month in 2021, who suffered from miofacial pain due to dysfunction in the temporomandibular joint. These were assigned in an alternating way in two therapeutic groups of 40 members each one: that of study, to which electroacupuncture was applied, and that of control, which received conventional pharmacological medication; then, they were clinically evaluated at the third, fifth, seventh and tenth days after the therapy. The variables were statistically processed applying the percentage as summary measure and the chi-square test to estimate differences as for the average time of good evolution, with a level of significance of 0.05. Results: Before beginning the therapy, the pain was intense in most of the patients of both groups; however, at the third day of the therapies, the evolution had been good in 45.0 % of the study group and 32.5 % of the control group, and the fifth day this percentage had increased at 60.0 in those that received electroacupuncture, but stayed equally in those that were treated conventionally. When concluding the intervention recession or relief of the miofacial pain in 97.5 % of the cases and in 90.0 % of the controls was achieved. Conclusions: The electroacupuncture was clinically more effective than the conventional medication to palliate the miofacial pain caused by the temporomandibular disorders, with a less average time of good therapeutic response.

RESUMEN Introducción: Los trastornos temporomandibulares constituyen una condición dolorosa que afecta los músculos de la masticación, la articulación temporomandibular, así como varias estructuras anatómicas del sistema estomatognático. Objetivo: Evaluar la efectividad de la electroacupuntura en pacientes con síndrome de dolor miofacial asociado a disfunción de la articulación temporomandibular. Métodos: Se realizó un estudio cuasiexperimental de intervención terapéutica en 80 pacientes asistidos en el Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde noviembre del 2018 hasta igual mes de 2021, quienes padecían dolor miofacial por disfunción en las articulaciones temporomandibulares. Estos fueron asignados de forma alterna en dos grupos terapéuticos de 40 integrantes cada uno: el de estudio, al que se le aplicó electroacupuntura, y el de control, el cual recibió medicación farmacológica convencional; luego, se les fue evaluando clínicamente al tercero, quinto, séptimo y décimo días de iniciadas las terapias. Las variables fueron procesadas estadísticamente aplicando el porcentaje como medida de resumen y la prueba de la Χ2 para estimar diferencias en cuanto al tiempo promedio de buena evolución, con un nivel de significación de 0,05. Resultados: Antes de comenzar los tratamientos, el dolor era intenso en la mayoría de los pacientes de ambos grupos; sin embargo, al tercer día de iniciada la intervención terapéutica, la evolución había sido buena en 45,0 % del grupo de estudio y 32,5 % del grupo de control; al quinto día este porcentaje había aumentado a 60,0 en los que recibieron electroacupuntura, pero se mantuvo igual en los que fueron tratados convencionalmente. Al finalizar la intervención se había logrado la recesión o el alivio del dolor miofacial en 97,5 % de los casos y en 90,0 % de los controles. Conclusiones: La electroacupuntura resultó clínicamente más efectiva para paliar el dolor miofacial producido por los trastornos temporomandibulares, con un menor tiempo promedio de buena respuesta terapéutica.

RESUMO Antecedentes: A acupuntura é um tratamento para a dor neuropática, mas seu mecanismo permanece obscuro. Estudos anteriores mostraram que a analgesia foi induzida em ratos com dor neuropática quando o conteúdo de adenosina da medula espinhal aumentou após a eletroacupuntura (EA); no entanto, o mecanismo por trás desse aumento induzido por eletroacupuntura não foi esclarecido. Objetivo: Este estudo teve como objetivo determinar o papel que a ecto-5'-nucleotidase desempenha na analgesia induzida por EA para dor neuropática. Métodos: Realizamos eletroacupuntura no ponto de acupuntura de Zusanli no sétimo dia após estabelecer um modelo de rato de dor neuropática induzida por lesão de constrição crônica. Observamos o limiar de retirada mecânica e o limiar de dor térmica, e detectamos a expressão de ecto-5'-nucleotidase na medula espinhal usando Western blot. Modelos de ratos com lesão de constrição crônica foram injetados intraperitonealmente com α, β-metilenadenosina 5'-difosfato, um inibidor de ecto-5'-nucleotidase, 30 min antes da eletroacupuntura. O conteúdo de adenosina da medula espinhal foi detectado por meio de cromatografia líquida de alta eficiência. Por último, o agonista do receptor de adenosina A1 N6-ciclopentiladenosina foi injetado por via intratecal no edema lombar dos ratos, e a retirada mecânica e os limiares de dor térmica foram reavaliados. Resultados: Analgesia e aumento da expressão de ecto-5'-nucleotidase e conteúdo de adenosina na medula espinhal foram observados 1 h após a eletroacupuntura. α, β-metilenadenosina 5'-difosfato foi capaz de inibir a sobrerregulação do conteúdo de adenosina e analgesia induzida por eletroacupuntura. Após administração de N6-ciclopentiladenosina, a analgesia induzida por eletroacupuntura foi restaurada. Conclusões: Nossos resultados sugerem que a eletroacupuntura em Zusanli pode produzir analgesia em modelos de ratos com lesão de constrição crônica, possivelmente por meio do aumento da expressão de ecto-5'-nucleotidase induzida por eletroacupuntura, levando ao aumento da expressão de adenosina na medula espinhal.

ABSTRACT Background: Acupuncture is a treatment for neuropathic pain, but its mechanism remains unclear. Previous studies showed that analgesia was induced in rats with neuropathic pain when their spinal cord adenosine content increased after electroacupuncture (EA); however, the mechanism behind this electroacupuncture-induced increase has not been clarified. Objective: This study aimed to determine the role that ecto-5’-nucleotidase plays in EA-induced analgesia for neuropathic pain. Methods: We performed electroacupuncture at the Zusanli acupoint on the seventh day after establishing a rat model of neuropathic pain induced through chronic constriction injuries. We observed the mechanical withdrawal threshold and thermal pain threshold and detected the expression of ecto-5’-nucleotidase in the spinal cord using Western blot. Chronic constriction injury rat models were intraperitoneally injected with α,β-methyleneadenosine 5'-diphosphate, an ecto-5’-nucleotidase inhibitor, 30 min before electroacupuncture. The adenosine content of the spinal cord was detected using high-performance liquid chromatography. Lastly, the adenosine A1 receptor agonist N6-cyclopentyladenosine was intrathecally injected into the lumbar swelling of the rats, and the mechanical withdrawal and thermal pain thresholds were reevaluated. Results: Analgesia and increased ecto-5’-nucleotidase expression and adenosine content in the spinal cord were observed 1 h after electroacupuncture. α,β-methyleneadenosine 5'-diphosphate was able to inhibit upregulation of adenosine content and electroacupuncture-induced analgesia. After administration of N6-cyclopentyladenosine, electroacupuncture-induced analgesia was restored. Conclusions: Our results suggest that electroacupuncture at Zusanli can produce analgesia in chronic constriction injury rat models, possibly via the increased ecto-5’-nucleotidase expression induced through electroacupuncture, thus leading to increased adenosine expression in the spinal cord.

Resumo Objetivo: avaliar as evidências científicas sobre a efetividade das terapias complementares no controle de sintomas do trato urinário inferior na população masculina adulta e idosa. Método: revisão sistemática desenvolvida de acordo com o checklist PRISMA. A busca foi realizada nas bases de dados CINAHL, Embase, LILACS, PEDro, PubMed, Web of Science e Google Scholar. Resultados: foram identificados 585 registros e selecionados 12 ensaios clínicos que atenderam aos critérios de inclusão. Os desfechos considerados pelos estudos para analisar a efetividade das terapias complementares foram questionários validados de avaliação da gravidade dos sintomas do trato urinário inferior (sensação de esvaziamento incompleto da bexiga, micções frequentes, fluxo intermitente, fluxo fraco, dor ou dificuldade na micção, noctúria e urgência) e parâmetros da urodinâmica. Os estudos analisaram as terapias complementares fitoterapia (n=8) e eletroacupuntura (n=4). Seis estudos relacionados à fitoterapia mostraram significância estatística. A eletroacupuntura mostrou melhora significativa dos sintomas em dois estudos. Conclusão: a fitoterapia foi efetiva para controle dos sintomas frequência, urgência, noctúria, esvaziamento incompleto, intermitência, fluxo fraco e esforço para iniciar a micção. Para confirmação da efetividade da eletroacupuntura ainda serão necessárias pesquisas com metodologias bem delineadas para sanar as divergências entre os estudos desta revisão.

Abstract Objective: to evaluate diverse scientific evidence on the effectiveness of complementary therapies in the control of lower urinary tract symptoms in the adult and aged male population. Method: a systematic review developed according to the PRISMA checklist. The search was performed in the CINAHL, Embase, LILACS, PEDro, PubMed, Web of Science and Google Scholar databases. Results: a total of 585 records were identified and 12 clinical trials were selected that met the inclusion criteria. The outcomes considered by the studies for analyzing effectiveness of the complementary therapies were validated questionnaires to assess the severity of the lower urinary tract symptoms (sensation of incomplete bladder emptying, frequent urination, intermittent flow, weak flow, pain or difficulty urinating, nocturia and urgency) and urodynamics parameters. The studies analyzed the complementary phytotherapy (n=8) and electroacupuncture (n=4) therapies. Six studies related to phytotherapy showed statistical significance. Electroacupuncture showed a significant improvement in the symptoms in two studies. Conclusion: pytotherapy was effective to control the simptoms related to frequency, urgency, nocturia, incomplete emptying, intermittence, weak flow and effort to initiate urination. To confirm the effectiveness of electroacupuncture, research studies with well-designed methodologies will also be necessary to resolve the divergences between the studies of this review.

Resumen Objetivo: evaluar la evidencia científica sobre la efectividad de las terapias complementarias para el control de los síntomas del tracto urinario inferior en la población masculina adulta y adulta mayor. Método: revisión sistemática desarrollada según la checklist PRISMA. La búsqueda se realizó en las bases de datos CINAHL, Embase, LILACS, PEDro, PubMed, Web of Science y Google Scholar. Resultados: se identificaron 585 registros y se seleccionaron 12 ensayos clínicos que cumplían con los criterios de inclusión. Los resultados que los estudios consideraron para analizar la efectividad de las terapias complementarias fueron cuestionarios validados que evaluaban la gravedad de los síntomas del tracto urinario inferior (sensación de vaciado incompleto de la vejiga, micción frecuente, flujo intermitente, flujo débil, dolor o dificultad para orinar, nicturia y urgencia) y parámetros urodinámicos. Los estudios analizaron las terapias complementarias fitoterapia (n=8) y electroacupuntura (n=4). Seis estudios relacionados con la fitoterapia demostraron significación estadística. La electroacupuntura demostró una mejoría significativa de los síntomas en dos estudios. Conclusión: la fitoterapia fue efectiva para controlar los síntomas de frecuencia, urgencia, nicturia, vaciado incompleto, intermitencia, flujo débil y esfuerzo para iniciar la micción. Para confirmar la efectividad de la electroacupuntura, aún es necesario que se realicen investigaciones con metodologías bien diseñadas para resolver las diferencias entre los estudios de esta revisión.

Abstract Background: G protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia. Methods: The mice model of inflammatory pain was built by subcutaneous injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and down-regulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron–specific promoters, and microglial activation and neuroinflammation were evaluated by real–time PCR. Results: Intraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA–induced mechanical allodynia. The effects of EA were markedly weakened by non–cell–specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron–specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA–induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA–induced inflammatory pain. Conclusion: The restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.

Abstract Background: Accumulating evidence has demonstrated that the electroacupuncture (EA) stimulation could effectively alleviate neuropathic pain. The medial prefrontal cortex (mPFC) is a vital part of the cortical representation of pain in the brain, and its glucose metabolism is mostly affected in the progression of pain. However, the central mechanism of EA analgesia remains unclear. Methods: Fifty-four male SD rats were equally randomized into sham surgery (Sham) group, chronic constriction injury (CCI) group and EA stimulation (EA) group. The CCI model, involving ligature of the right sciatic nerve, was established in all animals except the Sham group. EA stimulation was applied on the right side acupoints of Huantiao (GB30) and Yanglingquan (GB34) in the EA group. Paw withdrawal threshold (PWT) and paw thermal withdrawal latency (PWL) were measured. The 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) was used to evaluate glucose metabolism changes in the mPFC. The expression of glucose transporter 3 (GLUT-3) in the mPFC was determined by immune histochemistry and ELISA. Results: Comparing with CCI groups, EA treatment was obviously reversed CCI-induced mechanical allodynia (P < 0.01), thermal hyperalgesia (P < 0.01) and the increase of glucose metabolism in the left mPFC (P < 0.05). Furthermore, EA treatment significantly decreased the protein expression of GLUT-3 in the left mPFC (P < 0.01). Conclusions: Our results indicate that EA analgesia effect may be related to suppressing the glucose metabolism and GLUT-3 expression in the mPFC. This study could provide a potential insight into the central mechanisms involved in the analgesic effect of EA.

Abstract Pelvic floor disorders are one of the most common complications in male patients with spinal cord injury. The aim of this review was to analyse the available evidence on the efficacy of different treatments used for pelvic floor dysfunctions in men with incomplete spinal cord injuries. The Scopus, Medline, PEDro, Web of Science, Dialnet, Pubmed and Cochrane databases were consulted for papers in Spanish and English published in the last twenty years. Fifteen articles were included, comprising a total of 706 male patients with incomplete spinal cord injury. In male patients with neurogenic bladder and erectile dysfunction, the best results were obtained with neuromodulation and combined treatments (electrotherapy or acupuncture / electroacupuncture with catheterization or bladder training).

Resumen Los problemas del suelo pélvico son una de las complicaciones más frecuentes en pacientes de sexo masculino con lesión medular. El objetivo de esta revisión es analizar la evidencia disponible sobre la eficacia de los distintos tratamientos que se pueden emplear en las disfunciones del suelo pélvico en varones con lesión medular incompleta. Se consultaron las bases de datos Scopus, Medline, PEDro, Web of Science, Dialnet, Pubmed y Cochrane, en castellano e inglés en los últimos veinte años. Se incluyeron quince artículos con un total de 706 pacientes varones con lesión medular incompleta. La neuromodulación y la combinación de tratamientos (electroterapia o acupuntura / electroacupuntura con cateterismo o entrenamiento de vejiga) reportan los mejores resultados en vejigas neurógenas y disfunciones eréctiles.

RESUMO Introdução: A acupuntura tem sido amplamente utilizada para alívio de dor. No entanto, seus mecanismos são muito pouco conhecidos. Objetivo: Investigar a relação entre o efeito analgésico da eletroacupuntura e a regulação da expressão de adenosina e de substância P. Métodos: Utilizou-se um modelo de dor inflamatória crônica em ratos por injeção única do Adjuvante Completo de Freund e, em seguida, os animais foram tratados com eletroacupuntura diariamente. Foram aplicadas sete sessões bilaterais de eletroacupuntura (ST36 e BL60, 0,5 a 1,5 mA, força inicial de 0,5 mA, aumentada em 0,5 mA a cada 10 minutos, 30 minutos por sessão, uma sessão por dia) em ratos com Adjuvante Completo de Freund, por sete dias. O efeito analgésico da eletroacupuntura foi avaliado pela medida do limiar de retirada da pata em ratos que receberam estimulações mecânica e térmica. Resultados: A estimulação diária com eletroacupuntura aumentou efetivamente o limiar de retirada da pata em ratos com Adjuvante Completo de Freund. A eletroacupuntura aumentou o nível de adenosina na região zusanli. Estudos posteriores mostraram que a eletroacupuntura poderia diminuir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alpha, interleucina-1β, interleucina-6 e CD68 nos gânglios da raiz dorsal. Curiosamente, a injeção direta de antagonistas do receptor de adenosina A1 ou de substância P, ou a transecção da raiz do nervo dorsal, podem prejudicar significativamente as ações analgésicas induzidas pela eletroacupuntura em ratos com Adjuvante Completo de Freund e reduzir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alfa, interleucina-1β, interleucina-6 e CD68. Por fim, confirmamos que a injeção direta de um agonista do receptor da adenosina A1 reproduziu os efeitos analgésicos da eletroacupuntura. Conclusão: Nossos resultados indicam a regulação da secreção da substância P mediada pela adenosina. A via mediada pela substância P pode estar envolvida no processo de analgesia por eletroacupuntura em ratos.

ABSTRACT Background: Acupuncture has been widely used for alleviating pain. However, its mechanisms remain largely enigmatic. Objective: In the present study, we focused on whether the analgesic effect of electroacupuncture is related to its regulation on adenosine and substance P expression. Methods: We established chronic inflammatory pain model in rats through a single injection of Complete Freund’s Adjuvant, and then we treated animals using daily electroacupuncture. We applied seven bilateral sessions of electroacupuncture (ST36 and BL60, 0.5 to 1.5 mA, initial strength of 0.5 mA, increased by 0.5 mA every 10 minutes, for 30 minutes per session, one section per day) to Complete Freund’s Adjuvant rats for seven days. The analgesic effect of electroacupuncture was evaluated by measuring paw withdrawal threshold in rats that received mechanical and thermal stimulation. Results: Daily electroacupuncture stimulation effectively increased paw withdrawal threshold in Complete Freund’s Adjuvant rats. Electroacupuncture increased the adenosine level in zusanli. A further study showed that electroacupuncture could decrease substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68 levels in dorsal root ganglion. Interestingly, direct injection of adenosine A1 or substance P receptor antagonists, or dorsal nerve root transection could significantly impair electroacupuncture induced analgesic actions in Complete Freund’s Adjuvant rats could and reduce the levels of substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68. Finally, we confirmed that direct injection of adenosine A1 receptor agonist replicated the analgesic effect of electroacupuncture. Conclusion: Our results indicate regulation of adenosine-mediated substance P secretion. Substance P-mediated pathway may be involved in the analgesia process by electroacupuncture in rats.