Magnetic Resonance as a Method for Diagnosis for Traumatic Lesions by Brachial Plexus Avulsion / Ressonância magnética como método para diagnóstico das lesões traumáticas por avulsão do plexo braquial

Abstract Objective The incidence of traumatic brachial plexus injuries has been increasing considerably in Brazil, mainly due to the increase in the number of motorcycle accidents. The aim of the present study is to evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) in the diagnosis of brachial plexus avulsion lesions, comparing it with the findings of physical and intraoperative examination. Methods A total of 16 patients with brachial plexus injury were prospectively evaluated and treated at the hand surgery outpatient clinic from our service. All patients underwent MRI of the brachial plexus, and the findings were inserted on a table, as well as the physical examination data, and part of the patients had the plexus evaluated intraoperatively. Results In the present study, the accuracy of MRI in the identification of root avulsion was 100%, with 100% sensitivity and specificity when comparing imaging with surgical findings. Conclusion Magnetic resonance imaging showed high sensitivity and specificity, confirmed by intraoperative findings, which allows considering this test as the gold standard in the diagnosis of avulsion in traumatic brachial plexus injuries.

Resumo Objetivo A incidência de lesões traumáticas do plexo braquial vem aumentando consideravelmente no Brasil, principalmente devido ao aumento do número de acidentes de motocicleta. O objetivo do presente estudo é avaliar a sensibilidade e a especificidade da ressonância magnética (RM) no diagnóstico das lesões por avulsão do plexo braquial, comparando com os achados do exame físico e do intraoperatório. Métodos Foram avaliados prospectivamente 16 pacientes com lesão do plexo braquial atendidos no ambulatório de cirurgia da mão de nosso serviço. Todos os pacientes foram submetidos ao exame de RM do plexo braquial e os achados foram inseridos em uma tabela, assim como os dados do exame físico, e parte dos pacientes teve o plexo avaliado intraoperatoriamente. Resultados No presente estudo, a acurácia da RM na identificação de avulsão de raízes foi de 100%, com 100% de sensibilidade e especificidade comparando-se achados da imagem e cirúrgicos. Conclusão A RM mostrou alta sensibilidade e especificidade, confirmadas por achados intraoperatórios, o que permite considerar este exame como padrão outro no diagnóstico de avulsão nas lesões traumáticas do plexo braquial.

Efeitos de um protocolo de exercícios de força, flexibilidade e equilíbrio nas lesões de nervos periféricos: um estudo de caso / Effects of a strength, flexibility, and balance exercise protocol on peripheral nerve injuries: a case study

Introdução: As lesões de nervos periféricos são mais frequentes em membros superiores (MMSS), que são importantes para as atividades de vida diárias, equilíbrio e reflexos de proteção. Alterações no sistema de controle postural podem impactar na funcionalidade desses indivíduos. Portanto, é necessário alternativas para melhorar as alterações secundárias à lesão. Objetivo: Avaliar os efeitos de um protocolo de exercícios de força, flexibilidade e equilíbrio em paciente com lesão de nervos periféricos. Métodos: Estudo de caso de abordagem quantitativa realizado na Clínica Escola de Fisioterapia da Unochapecó, entre abril e julho de 2021, totalizando 30 intervenções de 60 minutos cada. A amostra foi constituída por um paciente do sexo masculino, 46 anos com diagnóstico de lesão de nervos periféricos no MMSS direito, decorrente de um acidente motociclístico. Foi realizada avaliação inicial, aplicação do protocolo, após a realização das escalas e testes: BESTest, MiniBESTest, Romberg-Barré, Dinamometria manual isométrica, Teste de Sentar e Alcançar e Mini-Exame do Estado Mental. O protocolo continha exercícios de força, flexibilidade e equilíbrio. Os dados foram analisados através de estatística descritiva comparativa, antes e após o protocolo (média e porcentagem). Resultados: Houve melhora na força muscular, flexibilidade toracolombar (aumento de 13 cm "61,90%") e testes de equilíbrio (15,81% BESTest, 21,42% MiniBESTest e 67,16% Romberg-Barré). Conclusão: O protocolo de exercícios refletiu positivamente na melhora da flexibilidade, força muscular e equilíbrio do paciente, tornando-se uma alternativa viável para melhorar as alterações secundárias a lesão. (AU)

Research progress of dental pulp stem cells for peripheral nerve injury repair / 中华口腔医学杂志

Peripheral nerve injuries are mainly related to severe trauma, fracture and tumor surgery, leading to reduced quality of life and impaired physical and mental health. The repair of peripheral nerve still faces great challenges in clinic, and the research on the regeneration and repair of peripheral nerve has become a hot issue in related disciplines. Cell therapy plays an irreplaceable role in tissue regeneration and repair. Schwann cells are ideal cells for peripheral nerve repair, but their limited sources inhibit the clinical application. Dental pulp stem cells are derived from neural crest, which provides a new cell source for nerve regeneration. The purpose of this article is to review the research progress of dental pulp stem cells for peripheral nerve repair.

Local vibration therapy promotes the recovery of nerve function in rats with sciatic nerve injury / 中西医结合学报

OBJECTIVE@#It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury, but the optimized parameters and effective mechanism were unclear. In the present study, we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury (SNI).@*METHODS@#Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups: sham group, SNI group, SNI + A-1 mm group, SNI + A-2 mm group, and SNI + A-4 mm group (A refers to the amplitude; n = 10 per group). Starting on the 7th day after model initiation, local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1, 2 or 4 mm for 5 min. The sciatic function index (SFI) was assessed before surgery and on the 7th, 14th, 21st and 28th days after surgery. Tissues were harvested on the 28th day after surgery for morphological, immunofluorescence and Western blot analysis.@*RESULTS@#Compared with the SNI group, on the 28th day after surgery, the SFIs of the treatment groups were increased; the difference in the SNI + A-2 mm group was the most obvious (95% confidence interval [CI]: [5.86, 27.09], P < 0.001), and the cross-sectional areas of myocytes in all of the treatment groups were improved. The G-ratios in the SNI + A-1 mm group and SNI + A-2 mm group were reduced significantly (95% CI: [-0.12, -0.02], P = 0.007; 95% CI: [-0.15, -0.06], P < 0.001). In addition, the expressions of S100 and nerve growth factor proteins in the treatment groups were increased; the phosphorylation expressions of ERK1/2 protein in the SNI + A-2 mm group and SNI + A-4 mm group were upregulated (95% CI: [0.03, 0.96], P = 0.038; 95% CI: [0.01, 0.94], P = 0.047, respectively), and the phosphorylation expression of Akt in the SNI + A-1 mm group was upregulated (95% CI: [0.11, 2.07], P = 0.031).@*CONCLUSION@#Local vibration therapy, especially with medium amplitude, was able to promote the recovery of nerve function in rats with SNI; this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.

Claudin 14/15 play important roles in early wallerian degeneration after rat sciatic nerve injury / 中华创伤杂志(英文版)

PURPOSE@#Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro.@*METHODS@#Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD.@*RESULTS@#It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered.@*CONCLUSION@#Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.

Low-intensity extracorporeal shock wave therapy promotes recovery of sciatic nerve injury and the role of mechanical sensitive YAP/TAZ signaling pathway for nerve regeneration / 中华医学杂志(英文版)

BACKGROUND@#Histological and functional recovery after peripheral nerve injury (PNI) is of significant clinical value as delayed surgical repair and longer distances to innervate terminal organs may account for poor outcomes. Low-intensity extracorporeal shock wave therapy (LiESWT) has already been proven to be beneficial for injured tissue recovery on various pathological conditions. The objective of this study was to explore the potential effect and mechanism of LiESWT on PNI recovery.@*METHODS@#In this project, we explored LiESWT's role using an animal model of sciatic nerve injury (SNI). Shockwave was delivered to the region of the SNI site with a special probe at 3 Hz, 500 shocks each time, and 3 times a week for 3 weeks. Rat Schwann cells (SCs) and rat perineurial fibroblasts (PNFs) cells, the two main compositional cell types in peripheral nerve tissue, were cultured in vitro, and LiESWT was applied through the cultured dish to the adherent cells. Tissues and cell cultures were harvested at corresponding time points for a reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence staining. Multiple groups were compared by using one-way analysis of variance followed by the Tukey-Kramer test for post hoc comparisons.@*RESULTS@#LiESWT treatment promoted the functional recovery of lower extremities with SNI. More nerve fibers and myelin sheath were found after LiESWT treatment associated with local upregulation of mechanical sensitive yes-associated protein (YAP)/transcriptional co-activator with a PDZ-binding domain (TAZ) signaling pathway. In vitro results showed that SCs were more sensitive to LiESWT than PNFs. LiESWT promoted SCs activation with more expression of p75 (a SCs dedifferentiation marker) and Ki67 (a SCs proliferation marker). The SCs activation process was dependent on the intact YAP/TAZ signaling pathway as knockdown of TAZ by TAZ small interfering RNA significantly attenuated this process.@*CONCLUSION@#The LiESWT mechanical signal perception and YAP/TAZ upregulation in SCs might be one of the underlying mechanisms for SCs activation and injured nerve axon regeneration.

Assessment of the Effects of Swimming as a Postoperative Rehabilitation on Nerve Regeneration of Wistar Rats Submitted to Grafting of Autologous Nerves after Injury to the Sciatic Nerve / Avaliação dos efeitos da natação como reabilitação pós-operatória na regeneração nervosa de ratos da linhagem Wistar submetidos a enxerto de nervos autólogos após lesão do nervo ciático

Abstract Objective To evaluate the effects of swimming on nerve regeneration after sciatic nerve injury in Wistar rats. Methods A total of 30 Wistar rats was divided into 3 groups: Sham + Nat group animals that were not submitted to graft surgery and were submitted to swimming (n = 10); Graft group: animals submitted to autologous sciatic nerve graft (n = 10); and Graft + Nat group: animals submitted to autologous sciatic nerve graft surgery and to swimming (n = 10). The results were analyzed on the software (GraphPad Software, San Diego, CA, USA). Results In the first evaluation, all sciatic functional index (SFI) values were similar (p = 0.609). Thirty days after the surgical procedure, we observed differences between all the comparisons: Sham + Nat (−34.64 ± 13.89) versus Graft (−145.9 ± 26.06); Sham + Nat versus Graft + Nat (−89.40 ± 7.501); Graft (−145.9 ± 26.06) versus Graft + Nat (−89.40 ± 7.501). In the measurements (60 and 90 days), there was no statistical difference between the Graft and Graft + Nat groups, with significantly lower values in relation to the control group (p < 0.001). The number of motor neurons presented differences in the comparisons between the Sham + Nat and Graft groups (647.1 ± 16.42 versus 563.4 ± 8.07; p < 0.05), and between the Sham + Nat and Graft + Nat groups (647.1 ± 16.42 versus 558.8 ± 14.79; p < 0.05). There was no difference between the Graft and Graft + Nat groups. Conclusion Animals submitted to the swimming protocol after the sciatic nerve grafting procedure did not present differences in the SFI values and motor neuron numbers when compared to the control group. Therefore, this type of protocol is not efficient for the rehabilitation of peripheral nerve lesions that require grafting. Therefore, further studies are needed.

Resumo Objetivo Avaliar os efeitos da natação na regeneração nervosa após a lesão do nervo ciático em ratos Wistar. Métodos Um total de 30 ratos Wistar foram divididos em 3 grupos: grupo Sham + Nat: animais que não foram submetidos à cirurgia de enxerto e foram submetidos à natação (n = 10); grupo Enxerto: animais que foram submetidos à cirurgia de enxerto autólogo de nervo ciático (n = 10); e grupo Enx + Nat: animais submetidos à cirurgia de enxerto autólogo de nervo ciático e à natação (n = 10). Os resultados foram analisados pelo software GraphPad Prism 5.0 (GraphPad Software, San Diego, CA, EUA). Resultados Na primeira avaliação, todos os valores do índice funcional do ciático (IFC) foram semelhantes (p = 0.609). Após 30 dias do procedimento cirúrgico, foram observadas diferenças entre todas as comparações: Sham + Nat (−34,64 ± 13,89) versus Enxerto (−145,9 ± 26,06), grupos Sham + Nat versus Enx + Nat (−89,40 ± 7,501), grupos Enxerto (−145,9 ± 26,06) versus Enx + Nat (−89,40 ± 7,501). Nas medidas (60 e 90 dias), não houve diferença estatística entre os grupos Enxerto e Enx + Nat, com valores significativamente menores em relação ao grupo controle (p < 0,001). O número de motoneurônios apresentou diferenças nas comparações entre os grupos Sham + Nat e Enxerto (647,1 ± 16,42 versus 563,4 ± 8,07; p < 0,05) e Sham + Nat e Enx + Nat (647,1 ± 16,42 versus 558,8 ± 14,79; p < 0,05), não havendo diferença entre os grupos Enxerto e Enx + Nat. Conclusão Os animais submetidos ao protocolo de natação após o procedimento de enxerto do nervo ciático não apresentaram diferenças nos valores de IFC e nos números de motoneurônios quando comparados com grupo controle. Portanto, este tipo de protocolo não é eficiente para reabilitação de lesões nervosas periféricas que necessitam de enxerto, sendo necessários novos estudos.

Criteria for assessing peripheral nerve injury. Behavioral and functional assessment in non-operated Wistar rats

Abstract Purpose To evaluate the normality pattern in functional tests of peripheral nerves. Methods Sixty female and sixty male Wistar rats were submitted to vibrissae movement and nictitating reflex for facial nerve; grooming test and grasping test for brachial plexus; and walking tracking test and horizontal ladder test for lumbar plexus. The tests were performed separately, with an interval of seven days between each. Results All animals showed the best score in vibrissae movement, nictitating reflex, grooming test, and horizontal ladder test. The best score was acquired for the first time in more than 90% of animals. The mean of strength on the grasping test was 133.46±12.08g for the right and 121.74±8.73g for the left anterior paw. There was a difference between the right and left sides. There was no difference between the groups according to sex. There is no statistical difference comparing all functional indexes between sex, independent of the side analyzed. The peroneal functional index showed higher levels than the sciatic and tibial functional index on both sides and sex. Conclusions The behavioral and functional assessment of peripheral nerve regeneration are low-cost, easy to perform, and reliable tests. However, they need to be performed by experienced researchers to avoid misinterpretation.

Eficácia da estimulação elétrica com corrente russa após neurorrafia término-lateral do nervo fibular comum: análise eletroneuromiográfica e de força muscular / Eficacia de la estimulación eléctrica con la corriente rusa tras la neurorrafia término-lateral del nervio fibular común: análisis electroneuromiográfico y de fuerza muscular muscular / Efficacy of electrical Russian current stimulation after end-to-side neurorrhaphy of the common fibular nerve: electroneuromyography and muscle strength analysis

RESUMO Lesões de nervos periféricos levam a perda funcional elevada no tecido muscular. Assim, muitas pesquisas têm investigado técnicas cirúrgicas, como neurorrafias, e recursos terapêuticos, como eletroestimulação, para melhorar a funcionalidade de um músculo reinervado após lesão periférica. Este estudo tem como objetivo investigar os efeitos da eletroestimulação com corrente russa (2.500Hz, 4ms, 10 seg. de contração por 20 seg. de relaxamento, modulação de 10Hz e 100 Hz) na recuperação funcional após secção e neurorrafia término-lateral do coto distal do nervo fibular comum à face lateral do nervo tibial em ratos. Foram utilizados 25 ratos Wistar, machos, com 80 dias de vida, fornecidos pelo Biotério Central da Universidade Sagrado Coração (Bauru, SP, Brasil). Os animais foram divididos aleatoriamente em cinco grupos: grupo-controle Inicial (GCI), grupo-controle final (GCF), grupo experimental não tratado (GENT), grupo neurorrafia término-lateral com estimulação russa (GNTLER) e grupo-controle desnervado (GCD). A corrente russa foi iniciada cinco dias após neurorrafia e aplicada no músculo tibial cranial do GNTLER, 3 vezes por semana, totalizando 36 sessões. A estimulação elétrica foi eficaz para aumentar a amplitude e diminuir a latência do músculo reinervado, além de aumentar a força muscular em comparação ao GCD. Diante disso, conclui-se que a eletroestimulação de média frequência (corrente russa) foi eficiente na recuperação funcional do músculo tibial cranial após neurorrafia término-lateral do nervo fibular comum.

RESUMEN Las lesiones de los nervios periféricos ocasionan una elevada pérdida funcional en el tejido muscular. De esta manera, en muchos estudios se han investigado técnicas quirúrgicas, como neurorrafias, y recursos terapéuticos, como la electroestimulación, para mejorar la funcionalidad del músculo reinervado tras una lesión periférica. El presente estudio tiene como objetivo investigar los efectos de la electroestimulación con corrente rusa (2.500Hz, 4ms, 10 seg. de contracción por 20 seg. de relajación, modulación de 10Hz y 100Hz) en la recuperación funcional tras la sección y neurorrafia término-lateral del muñón distal del nervio fibular común en la parte lateral del nervio tibial en ratas. Se utilizaron 25 ratas Wistar, machos, con 80 días de vida, proporcionadas por el Biotério Central de la Universidade do Sagrado Coração (Bauru, SP, Brasil). Se dividieron aleatoriamente los animales en cinco grupos: grupo de control inicial (GCI), grupo de control final (GCF), grupo experimental no tratado (GENT), grupo de neurorrafia término-lateral con estimulación rusa (GNTLER) y grupo de control denervado (GCD). La corriente rusa se inició cinco días tras la neurorrafia, siendo que la aplicó al músculo tibial craneal del GNTLER 3 veces a la semana, con un total de 36 sesiones. La estimulación eléctrica se mostró efectiva para aumentar la amplitud y disminuir la latencia del músculo reinervado, además de aumentar la fuerza muscular en comparación con el GCD. Por lo tanto, se concluye que la estimulación eléctrica de frecuencia media (corriente rusa) fue eficaz en la recuperación funcional del músculo tibial craneal tras la neurorrafia término-lateral del nervio fibular común.

ABSTRACT Peripheral nerve injury leads to a high functional loss of muscle tissue. Thus, many studies have investigated surgical techniques, such as neurorraphies, and therapeutic resources, such as electrical stimulation, to improve the functionality of reinnervated muscle after peripheral injury. This study aims to investigate the effects of electrical stimulation with Russian Current (2,500Hz, 4ms, 10:20 sec contraction/relaxation, modulated at 10Hz and 100Hz) in the functional recovery after section and end-to-side neurorrhaphy of the peroneal nerve distal stump common to the lateral face of the tibial nerve in rats. In this study, 25 male Wistar rats with 80 days of life were used, provided by the Universidade Sagrado Coração (USC), Bauru, SP, Brazil. The animals were randomly divided into five groups: Initial Control Group (ICG), Final Control Group (FCG), Untreated Experimental Group (UEG), End-to-Side Neurorrhaphy with Russian Stimulation Group (ENRSG), and Denervated Control Group (DCG). The Russian Current was started 5 days after neurorrhaphy and applied to the cranial tibial muscle of the ENRSG, 3 times a week, totaling 36 sessions. We observed that the electrical stimulation with Russian Current (ENRSG) was effective to increase amplitude (mV) and to decrease the latency (ms) of the reinnervated muscle, besides increasing the muscle strength when compared with the denervated control group. Therefore, we concluded that the average frequency electrical stimulation (Russian current) was efficient in the functional recovery of the cranial tibial muscle after the end-lateral neurorrhaphy of the common fibular nerve.

Anestesia neuroaxial y bloqueos regionales: lineamientos de anticoagulación para su aplicación / Neuraxial anesthesia and regional blocks: anticoagulation guidelines for its application

El personal de salud actualmente se enfrenta a múltiples desafíos en su práctica diaria, uno de ellos, es el manejo apropiado de anticoagulación de quienes por distintas causas demandan este tratamiento. Esta revisión bibliográfica ofrece pautas, especialmente para anestesiólogos, sobre el adecuado empleo de anticoagulantes y antiagregantes en pacientes que requieran anestesia/analgesia neuroaxial, bloqueos de plexo, bloqueos periféricos y catéteres; para evitar/prevenir complicaciones potencialmente devastadoras que el sangrado en el neuroaxis o sitios no compresibles podría ocasionar. Se ha basado en las actuales recomendaciones de ASRA 2018

The Health personnel currently face multiple challenges in their daily practice, one of them is the appropriate anticoagulation management of patients, who for various reasons demand this treatment. This literature review offers guidelines, especially for anesthesiologists, on the adequate use of anticoagulants and antiaggregants in patients requiring neuraxial anesthesia / analgesia, plexus blocks, peripheral blocks and catheters; to prevent / avoid potentially devastating complications that bleeding in neuroaxis or non-compressible sites could cause. It has been based on the current recommendations of ASRA 2018

Effect of electroacupuncture at "Jiaji" (EX-B 2) points combined with nerve mobilization on motor function and mRNA and protein expression of RhoA in rabbits with sciatic nerve injury / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) points combined with nerve mobilization on protein and mRNA expression of RhoA in rabbits with sciatic nerve injury, and to provide theoretical basis for the treatment of peripheral nerve injury by EA at "Jiaji" (EX-B 2) points combined with nerve mobilization.@*METHODS@#A total of 180 New Zealand rabbits were randomly divided into a normal control group, a model control group, a nerve mobilization group, an EA group, an EA plus nerve mobilization group, 36 rabbits in each group. Each group was further divided into a 1-week subgroup, 2-week subgroup and 4-week subgroup, 12 rabbits in each subgroup. The sciatic nerve injury model was made by clamping method. The rabbits in the normal control group did not receive any intervention. The rabbits in the model control group was normally fed after operation. The rabbits in the nerve mobilization group were treated with nerve mobilization; the manipulation lasted for 1 s and relaxed for 5 s, 10 times per day, 6 days per week. The rabbits in the EA group were treated with EA at "Jiaji" (EX-B 2) points (L-L), once a day, 30 min each time, 6 times per week. The rabbits in the EA plus nerve mobilization group were treated with EA at "Jiaji" (EX-B 2) points, followed by nerve mobilization. The function of sciatic nerve on the injured side was evaluated by toe tension reflex and modified Tarlov score; the tissues of corresponding segments of spinal cord L-L and sciatic nerve were taken; the expression of RhoA gene was detected by real-time PCR and the expression of RhoA protein was detected by Western Blot.@*RESULTS@#① Toe tension reflex and modified Tarlov score: at 1, 2 and 4 weeks, the scores in the model control group were lower than those in the normal control group (all 0.05); at 2 weeks, the expression in the nerve mobilization group was higher than that in the EA group (all <0.01); at 4 weeks, the expression in the nerve mobilization group was lower than that in the EA group (all <0.01).@*CONCLUSION@#The nerve mobilization and EA at "Jiaji" (EX-B 2) points could both promote the repair of injured sciatic nerve, which may be related to the down-regulation of RhoA expression, and the combination of the two methods has better effects.

Kir2.1 Channel Regulation of Glycinergic Transmission Selectively Contributes to Dynamic Mechanical Allodynia in a Mouse Model of Spared Nerve Injury / 神经科学通报·英文版

Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brush-evoked dynamic and filament-evoked punctate mechanical allodynia. Potassium channel 2.1 (Kir2.1), which exhibits strong inward rectification, is and regulates the activity of lamina I projection neurons. However, the relationship between Kir2.1 channels and mechanical allodynia is still unclear. In this study, we first found that pretreatment with ML133, a selective Kir2.1 inhibitor, by intrathecal administration, preferentially inhibited dynamic, but not punctate, allodynia in mice with spared nerve injury (SNI). Intrathecal injection of low doses of strychnine, a glycine receptor inhibitor, selectively induced dynamic, but not punctate allodynia, not only in naïve but also in ML133-pretreated mice. In contrast, bicuculline, a GABA receptor antagonist, induced only punctate, but not dynamic, allodynia. These results indicated the involvement of glycinergic transmission in the development of dynamic allodynia. We further found that SNI significantly suppressed the frequency, but not the amplitude, of the glycinergic spontaneous inhibitory postsynaptic currents (gly-sIPSCs) in neurons on the lamina II-III border of the spinal dorsal horn, and pretreatment with ML133 prevented the SNI-induced gly-sIPSC reduction. Furthermore, 5 days after SNI, ML133, either by intrathecal administration or acute bath perfusion, and strychnine sensitively reversed the SNI-induced dynamic, but not punctate, allodynia and the gly-sIPSC reduction in lamina IIi neurons, respectively. In conclusion, our results suggest that blockade of Kir2.1 channels in the spinal dorsal horn selectively inhibits dynamic, but not punctate, mechanical allodynia by enhancing glycinergic inhibitory transmission.

mTOR signaling pathway of spinal cord is involved in peripheral nerve injury-induced hyperalgesia in rats / 中南大学学报(医学版)

To investigate whether mammalian target of rapamycin (mTOR) signaling pathway is involved in peripheral nerve injury-induced hyperalgesia through activation of spinal dorsal astrocytes in rats.
 Methods: A total of 30 male Sprague-Dawley (SD) rats were randomly divided into 6 groups (n=5): the 1 day group (D1 group), the 4 days group (D4 group), the 7 days group (D7 group), the 14 days group (D14 group), the normal group and the sham group. The sciatic nerve chronic constriction injury (CCI) model was established in the D1, D4, D7 and D14 group. The normal group received no treatment while the sham group was only exposed the sciatic nerve. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured at the 1st, 4th, 7th, and 14th day after CCI in the different groups. Lumbar spinal cord were harvested on the 1st, 4th, 7th and 14th day in the D1, D4, D7, D14 group correspondingly, which were harvested on the 14th day in the normal group and the sham group. Distribution of mTOR in rat spinal cord was assessed by immunohistochemistry. The expressions of mTOR mRNA and protein in the spinal cord in different groups were determined by real-time PCR and Western blotting, respectively. Another 30 male intrathecal catheterized SD rats were randomly divided into 6 groups (n=5): a blank group, a CCI group, a CCI+early rapamycin (RAPA) group, a CCI+early dimethylsulfoxide (DMSO) group, a CCI+ later RAPA group, and a CCI+later DMSO group. The blank group didn't received any treatment; The CCI group was carried out the treatment of CCI model in the left hind limbs. 10 μL of 1% RAPA was given to the CCI+early RAPA group intrathecally at 4 hours after CCI for 3 days; the CCI+later RAPA group were treated with the same dose of RAPA on the 7th days after CCI for 3 days; the CCI+early DMSO group and the CCI+later DMSO group were injected with the same volume of 4% DMSO at the corresponding time as controls. The PWTL and PWMT were measured before and after intrathecal catheterization, and every other day after CCI. The lumbar spinal cords were selected and the expression of glial fibrillary acidic protein (GFAP) in spinal dorsal horn were examined by immunohistochemistry in the 14th day after CCI.
 Results: The immunohistochemistry positive particles of mTOR were widely distributed in the cytoplasm of the normal spinal neurons. Compared with the base line, the PWMT in the D14 group on the 1st, 4th, 7th and 14th day after CCI were significantly lower, and the PWTL on the 4th, 7th and 14th day after CCI were also significantly lower (P<0.05 or P<0.01). The expressions of mTOR mRNA and protein in the CCI groups (D1, D4, D7 and D14 group) were significantly increased than those in the normal group (P<0.05 or P<0.01). Compared with the CCI+early DMSO group, the PWMT and PWTL in the CCI+early RAPA group were obviously increased on 4th, 6th, 8th, 10th, 12th or 14th day after CCI (P<0.05 or P<0.01); compared with the CCI+later DMSO group, the PWMT and PWTL in the CCI+later RAPA group were also significantly increased at the 8th, 10th or 14th day after CCI (P<0.01 or P<0.05). The GFAP immunohistochemistry positive area and absorbance value in the dorsal horn of the lumbar spinal cord in the CCI rats were decreased in the CCI+early RAPA group compared with the CCI+early DMSO group (P<0.05 or P<0.01), and which were also decreased in the CCI+later RAPA group compared with the CCI+later DMSO group (P<0.05 or P<0.01).
 Conclusion: mTOR signaling pathway may be involved in hyperalgesia induced by peripheral nerve injury via spinal astrocyte activation in the dorsal horn of the spinal cord.

Spinal Nitric Oxide Synthase Type II Increases Neurosteroid-metabolizing Cytochrome P450c17 Expression in a Rodent Model of Neuropathic Pain

We have previously demonstrated that the neurosteroid dehydroepiandrosterone sulfate (DHEAS) induces functional potentiation of N-methyl-D-aspartate (NMDA) receptors via increases in phosphorylation of NMDA receptor GluN1 subunit (pGluN1). However, the modulatory mechanisms responsible for the expression of the DHEA-synthesizing enzyme, cytochrome P450c17 following peripheral nerve injury have yet to be examined. Here we determined whether oxidative stress induced by the spinal activation of nitric oxide synthase type II (NOS-II) modulates the expression of P450c17 and whether this process contributes to the development of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the expression of NOS-II in microglial cells and NO levels in the lumbar spinal cord dorsal horn at postoperative day 5. Intrathecal administration of the NOS-II inhibitor, L-NIL during the induction phase of neuropathic pain (postoperative days 0~5) significantly reduced the CCI-induced development of mechanical allodynia and thermal hyperalgesia. Sciatic nerve injury increased the expression of PKC- and PKA-dependent pGluN1 as well as the mRNA and protein levels of P450c17 in the spinal cord at postoperative day 5, and these increases were suppressed by repeated administration of L-NIL. Co-administration of DHEAS together with L-NIL restored the development of neuropathic pain and pGluN1 that were originally inhibited by L-NIL administration alone. Collectively these results provide strong support for the hypothesis that activation of NOS-II increases the mRNA and protein levels of P450c17 in the spinal cord, ultimately leading to the development of central sensitization and neuropathic pain induced by peripheral nerve injury.

Peripheral Neuropathies in Patients with Rhabdomyolysis: Clinical Characteristics and Electrodiagnostic Findings in the Acute/Subacute Stage

BACKGROUND: Rhabdomyolysis is a syndrome caused by injury to skeletal muscle and characterized by myalgia and swelling of the affected muscles. Peripheral nerve injury rarely occurs in patients with rhabdomyolysis. METHODS: We reviewed the medical records of 8 consecutive patients with peripheral neuropathies associated with rhabdomyolysis. We assessed the clinical characteristics and electrodiagnostic findings of eight patients. RESULTS: In seven patients, rhabdomyolysis occurred after prolonged immobilization. In one patient, blunt trauma was a cause of rhabdomyolysis. All patients presented with weakness and paresthesia in lower extremities and electrodiagnostic tests showed peripheral nerve injury suggesting sciatic neuropathy or lumbosacral plexopathy. Although rhabdomyolysis itself recovered completely in all patients, neurologic deficits from neuropathy recovered partially and slowly. CONCLUSIONS: Sciatic nerve or lumbosacral plexus was injured in all eight patients. Among the various causes of rhabdomyolysis, prolonged immobilization is associated with development of peripheral neuropathy.

Effects of tadalafil to prevent injury on corpus cavernosum after vascular or nervous peri-prostatic bundle injury. Experimental model in rats

Abstract Purpose: To evaluate the effects of tadalafil (TD) in preventing histological alterations of the corpus cavernosum caused by isolated lesions of cavernous nerve (ILCN) and artery (ILCA) in rats. Methods: Fifty male Wistar rats were randomly assigned in five groups: G1: control; G2: bilateral ILCN; G3: bilateral ILCA; G4: ILCN+TD; G5: ILCA+TD. The cavernous bodies were submitted to histomorphometry, immunohistochemistry and biochemical analysis. Results: Nerve density was significantly higher in G2 and G4 compared to control (22.62±2.84 and 19.53±3.47 vs. 15.72±1.82; respectively, p<0.05). Smooth muscle density was significantly lower in G2 and G3 in comparison to G1 (12.87±1.90 and 18.93±1.51 vs. 21.78±1.81, respectively; p<0.05). A significant decrease in the sinusoidal lumen area was observed in G2 compared to controls (5.01±1.62 vs. 9.88±3.66, respectively; p<0.05) and the blood vessel density was increased in G2 and G3 (29.32±4.13 e 20.80±2.47 vs. 10.13±2.71, p<0.05). Collagen density was higher in G3 compared to G1 (93.76±15.81 vs. 64.59±19.25; p<0.05). Conclusions: Histomorphometric alterations caused by ILCN were more intense than those produced by vascular injury, but the collagen analyses showed more fibrosis in animals with ILCA. TD was effective in preventing the majority of the alterations induced by the periprostatic bundle injury.

Anatomical study of pronator teres muscle innervation and clinical significance in nerve transfer / Estudio anatómico de la inervación del músculo pronador redondo y significado clínico en la transferencia nerviosa

The anatomical relationship of the median nerve and its innervation pattern are variable and may have direct implications in surgical procedures such as distal nerve transfers. The objective of this study was to evaluate the anatomical variations of pronator teres muscle (PTM) innervation and its clinical significance in nerve transfers. Data were collected regarding the number of median nerve branches, site of their origin, contribution with branches of other muscles and the possibility of transferring expendable branches of PTM to the anterior interosseous nerve (AIN) and radial nerve. The most common origin of the branches was proximal to the humeral intercondylar line. The presence of only one PTM branch was identified in 9 limbs, in which 6 was exclusive for this muscle. The majority of specimens presented more than one branch to the PTM, with two branches in 19, although only 6 of these did not share branches with other muscles. The proximal branch of the PTM was long enough to be transferred to the AIN in 23 limbs and branches of the radial nerve in all. These transfers were possible even during the forearm prone-supination and flexion-extension of the elbow. The use of the PTM branch may be considered for transfers in C7-T1 root injuries of the brachial plexus, with care regarding the availability of multiple PTM branches and tension to the AIN and radial nerve branches.

La relación anatómica del nervio mediano y su patrón de inervación son variables y pueden tener implicaciones directas en los procedimientos quirúrgicos, como las transferencias de los nervios distales. El objetivo de este estudio fue evaluar las variaciones anatómicas de la inervación del músculo pronador redondo (MPR) y su importancia clínica en las transferencias nerviosas. Se obtuvieron datos sobre el número de ramas del nervio mediano, el lugar de origen, la contribución con ramas de otros músculos y la posibilidad de transferir ramas prescindibles de la MPR al nervio interóseo anterior (NIA) y al nervio radial. El origen más común de las ramas fue proximal a la línea intercondilar humeral. Se identificó la presencia de una sola rama de MPR en 9 miembros superiores, de los cuales 6 fueron exclusivas para este músculo. La mayoría de los especímenes presentaron más de una rama al MPR, con dos ramas en 19 de ellos, aunque solamente 6 no compartían ramas con otros músculos. La rama proximal del MPR fue lo suficientemente larga como para ser transferida a la NIA en un total de 23 miembros superiores y ramas del nervio radial. Estas transferencias fueron posibles incluso en el antebrazo, durante la supinación y la flexiónextensión del codo. El uso de la rama MPR puede considerarse para transferencias en lesiones de raíz C7-T1 del plexo braquial, con cuidado en cuanto a la disponibilidad de múltiples ramas de MPR y tensión a la NIA y las ramas nerviosas radiales.

Laserpuntura na neuropatia periférica: efeitos na dor e qualidade de vida / Laserpuncture in peripheral neuropathy: effects on pain and quality of life

Introdução: A laserpuntura é utilizada para analgesia, embora os protocolos para aplicação na dor neuropática permaneçam contraditórios. Objetivo: Avaliar o efeito da laserpuntura na modulação da dor neuropática, impacto na qualidade de vida e processo inflamatório local. Material e métodos: Cinco pacientes com diagnóstico de lesão nervosa periférica e dor neuropática associada receberam aplicação do laser AlGaInP, 658 nm, 10 mW, 9 J/cm2, em acupontos especí­ficos, durante 15 sessões, 3 vezes na semana, por 50 minutos. A avaliação pré e pós-intervenção foi realizada pela Escala Visual Analógica, questionário para dor (McGill), questionário de qualidade de vida (SF-36), Índice de incapacidade de Oswestry e termografia. Resultados: Foi observada redução da média da pontuação na Escala Visual Analógica em 3 de 5 pacientes e redução da média de dor após 15 sessões. A avaliação pelo McGill mostrou redução nas dimensões afetivo, avaliativo e total. No questionário SF-36 foi observada melhora das dimensões Capacidade Funcional e Limitação por Aspectos Emocionais. No Índice de Oswestry observou-se redução da média da porcentagem e na termografia não houve diferença nos valores pré e pós-intervenção. Conclusão: Estes resultados sugerem eficácia da laserpuntura na redução da dor e melhora da qualidade de vida em pacientes com dor neuropática decorrente de lesão nervosa periférica. (AU)

Introduction: Laserpuncture is used for analgesia, although the protocols for use in neuropathic pain remain contradictory. Objective: To evaluate the effect of laserpuncture in modulating neuropathic pain, impact on quality of life and local inflammatory process. Methods: Five patients with peripheral nerve injury and neuropathic pain associated application received AlGaInP laser, 658 nm, 10 mW, 9 J/cm2 at specific acupoints for 15 sessions, 3 times a week for 50 minutes. The pre- and post-intervention were performed by Visual Analogue Scale, questionnaire for pain (McGill), quality of life questionnaire (SF-36), Oswestry disability index and thermography. Results: A significant reduction in Visual Analogue Scale score average was observed in 3 of 5 patients in addition to an overall reduction of average pain after 15 sessions. The evaluation by McGill showed reduction in affective, evaluative and overall dimensions. In the SF-36 questionnaire was observed an increase of the dimensions Functional Capacity and Emotional Aspects. In Oswestry Index a reduction was observed in the average percentage and in the thermography no difference was noticed in pre and post-intervention. Conclusion: These results suggest effectiveness of laser acupuncture in reducing pain and improving quality of life in patients with neuropathic pain due to peripheral nerve injury. (AU)

Diagnostic Usefulness of Neuromuscular Ultrasound in Anatomical Localization of Peripheral Nerve Injury: Detailed Lesion Localization Using Neuromuscular Ultrasound in a Patient with Traumatic Ulnar Nerve Injury at the Hand

In the evaluation of peripheral nerve injury, nerve conduction studies and needle electromyography mainly focus on anatomical localization and functional evaluation of lesions. Whereas neuromuscular ultrasound has an advantage in structural assessment of lesions. In addition, muscle ultrasound can also be used to demonstrate muscle denervation without causing pain. We report a case of traumatic ulnar nerve injury at hand in which muscle ultrasound contributed to precise localization by provided detailed information about the extent of muscle denervation.