The Role and Mechanism of Aspirin Combined with Rehabilitation Training in the Repair of Sciatic Nerve Injury and the Changes in the Schwannocytus (Schwann Cells) in Rats / Rol y Mecanismo de la Aspirina Combinados con Entrenamiento de Rehabilitación en la Reparación de la Lesión del Nervio Ciático y los Cambios en los Schwannocitos (Células de Schwann) en Ratas

SUMMARY: This study investigated the role and mechanism of aspirin combined with rehabilitation training in the nerve injury repair and Schwann cell changes in rats with sciatic nerve injury. Totally, 120 male healthy SD rats were randomly divided into sham, model, aspirin, and aspirin + rehabilitation groups, with 30 rats in each group. The sciatic nerve function index (SFI), photothermal pain tolerance threshold and inclined plane test results at 4, 6, and 8 weeks after operation were compared. The distance of sensory nerve regeneration and the expression of S100B protein in Schwann cells were analyzed. Compared with the sham group, the SFI of the model, aspirin, and aspirin+rehabilitation groups were significantly lower at 4, 6, and 8 weeks after operation. However, the aspirin and aspirin+rehabilitation groups had significantly higher SFI than the model group. The SFI at 6 and 8 weeks after operation was higher in the aspirin+rehabilitation group than that in the aspirin group (P<0.05). The photothermal pain tolerance threshold of the sham, aspirin, and aspirin+rehabilitation groups were significantly higher than those of the model group at 4, 6, and 8 weeks after operation (P<0.05). The inclination angles of the model, aspirin, and aspirin+rehabilitation groups were significantly lower than those of the sham group at 4, 6, and 8 weeks after operation, and the inclination angle of the aspirin+rehabilitation group was significantly higher than that of the model and aspirin groups (P<0.05). The sensory nerve regeneration distance in aspirin and aspirin+rehabilitation groups was higher than that in the sham and model groups (P<0.05). The expression of S100B protein in the aspirin and aspirin+rehabilitation groups was higher than that in the model group (P<0.05). Aspirin combined with rehabilitation training can promote the functional recovery of sciatic nerve injury, and the mechanism may be related to the increase of the expression of S100B protein in Schwann cells.

En este estudio se investigó el papel y el mecanismo que desempeña la aspirina combinada, con el entrenamiento de rehabilitación en la reparación de lesiones nerviosas y los cambios en los schwannocitos en ratas con lesiones en el nervio ciático. En total, 120 ratas SD macho sanas se dividieron aleatoriamente en cuatro grupos de 30 ratas en cada uno: simulación, modelo, aspirina y aspirina + rehabilitación. Se compararon el índice de función del nervio ciático (SFI), el umbral de tolerancia al dolor fototérmico y los resultados de la prueba del plano inclinado a las 4, 6 y 8 semanas después de la operación. Se analizó la distancia de regeneración del nervio sensorial y la expresión de la proteína S100B en los schwannocitos. En comparación con el grupo simulado, el SFI de los grupos modelo, aspirina y aspirina+rehabilitación fue significativamente menor a las 4, 6 y 8 semanas después de la operación. Sin embargo, los grupos de aspirina y aspirina + rehabilitación tuvieron un SFI significativamente más alto que el grupo modelo. El SFI a las 6 y 8 semanas después de la operación fue mayor en el grupo de aspirina + rehabilitación que en el grupo de aspirina (P<0,05). El umbral de tolerancia al dolor fototérmico de los grupos simulado, aspirina y aspirina+rehabilitación fue significativamente mayor que el del grupo modelo a las 4, 6 y 8 semanas después de la operación (P<0,05). Los ángulos de inclinación de los grupos modelo, aspirina y aspirina+rehabilitación fueron significativamente menores que los del grupo simulado a las 4, 6 y 8 semanas después de la operación, y el ángulo de inclinación del grupo aspirina+rehabilitación fue significativamente mayor que el de los grupos modelo y aspirina (P<0.05). La distancia de regeneración del nervio sensorial en los grupos de aspirina y aspirina+rehabilitación fue mayor que en los grupos simulado y modelo (P<0,05). La expresión de la proteína S100B en los grupos de aspirina y aspirina+rehabilitación fue mayor que en el grupo modelo (P<0,05). La aspirina combinada con el entrenamiento de rehabilitación puede promover la recuperación funcional de la lesión del nervio ciático, y el mecanismo puede estar relacionado con el aumento de la expresión de la proteína S100B en los schwannocitos.

Resultados de la neurólisis como tratamiento del dolor neuropático en pacientes con lesión del nervio ciático. Reporte de casos / Results of neurolysis for the treatment of neuropathic pain in patients with sciatic nerve Injury. Case report

Introducción: La lesión del nervio ciático puede ocasionar desde parestesias e hipoestesias, hasta dolor neuropático severo y parálisis. La neurólisis suele mejorar la función, el dolor y la calidad de vida de los pacientes. El objetivo de este estudio fue evaluar los resultados clínico-funcionales de una serie de pacientes con dolor neuropático por lesión del nervio ciático que no respondieron al tratamiento conservador y fueron sometidos a neurólisis. Materiales y métodos: Se analizó retrospectivamente una serie de pacientes sometidos a neurólisis del nervio ciático mayor entre marzo de 2009 y junio de 2018. El dolor pre- y posoperatorio se evaluó mediante la escala analógica visual y la escala de Likert. El tipo de dolor posoperatorio se evaluó con el cuestionario DN4 y la calidad de vida relacionada con la salud, con el cuestionario SF-36.Resultados:Se incluyó a 8 pacientes. A los 32 meses de seguimiento promedio (rango 14-66), el dolor había mejorado notablemente (promedio de 3 y 1,88 puntos en las escalas analógica visual y de Likert, respectivamente). El cuestionario DN4 arrojó un promedio de 3,75 puntos (rango 2-7). Según el SF-36, la "salud física" fue la variable con peores resultados (promedio 30,15).Conclusiones: La neurólisis, cuando se indica a pacientes con mala respuesta al tratamiento conservador, es un método que alivia el dolor y mejora la calidad de vida de los pacientes con dolor neuropático secundario a una lesión del nervio ciático. Nivel de Evidencia: IV

Introduction: Sciatic nerve injury may cause paresthesias and hypoesthesias, severe neuropathic pain, and paralysis. Neurolysis can improve function, pain, and quality of life for these patients. The objective of this paper is to evaluate the clinical-functional outcomes of a series of patients with neuropathic pain due to sciatic nerve injury that was refractory to conservative treatment in whom neurolysis was performed. materials and methods:A retrospective case series of patients operated on for neurolysis of the greater sciatic nerve between March 2009 and June 2018 was analyzed. Preoperative and postoperative pain were evaluated using the visual analog scale (VAS) and the Likert scale. The type of postoperative pain was evaluated using the DN4 questionnaire, and the health-related quality of life was measured with the SF-36 questionnaire. Results: Eight patients were included. All patients evolved with a notable improvement in pain, with an average of 3 and 1.88 points on the VAS and Likert scales, respectively. The mean follow-up was 32 months (range 14­66). The DN4 questionnaire showed an average of 3.75 points (range 2­7). According to the SF-36, "Physical Health" was the variable with the worst results, with an average of 30.15. Conclusions: Sciatic nerve neurolysis in patients with neuropathic pain due to sciatic nerve injury and poor response to conservative treatment may improve pain and quality of life. Level of Evidence: IV

High energy photobiomodulation therapy in the early days of injury improves sciatic nerve regeneration in mice / Aplicação de alta energia da terapia de fotobiomodulação nos primeiros dias de lesão otimiza a regeneração de nervo ciático em camundongos

INTRODUCTION: Different studies have evaluated the effects of electrophysical agents on regeneration after peripheral nerve injury. Among them, the most used in clinical and experimental research is photobiomodulation therapy (PBMT). OBJECTIVE: To analyze the effect of standard energy (16.8 J) of PBMT on peripheral nerve regeneration, applied at different periods after sciatic nerve injury in mice. METHODS: Thirty male Swiss mice were divided into six groups: naive; sham; control; LLLT-01 (660 nm, 16.8 J of total energy emitted in 1 day); LLLT-04 (660 nm, 4.2 J per day, 16.8 J of total energy emitted in 4 days); LLLT-28, (660 nm, 0.6 J per day, 16.8 J of total energy emitted over 28 days). The animals were evaluated using thermal hyperalgesia, Sciatic Functional Index (SFI), and Static Sciatic Index (SSI). Data were obtained at baseline and after 7, 14, 21, and 28 days after surgery. RESULTS: For the SFI and SSI, all groups showed significant differences compared to the control group, and the LLLT-04 group presented the best results among those receiving PBMT. In the assessment of thermal hyperalgesia, there was a significant difference in the 14th day of evaluation in the LLLT-04 group. CONCLUSION: The application of 16.8 J was useful in sciatic nerve regeneration with an improvement of hyperalgesia, with higher efficacy when applied in four days (4.2 J/day).

INTRODUÇÃO: Estudos avaliaram os efeitos de diferentes terapias aplicadas após lesão nervosa periférica, com o intuito de promover a regeneração local. Dentre elas, a mais utilizada em pesquisa clínica e experimental é a terapia de fotobiomodulação (TFBM). OBJETIVO: Analisar o efeito da fotobiomodulação (16,8 J) na regeneração nervosa periférica, aplicada em diferentes regimes após a lesão do nervo ciático em camundongos. MÉTODOS: Foram utilizados trinta camundongos machos (Swiss) divididos em: naive; sham; controle; LBI-01 (660 nm, 16,8 J de energia total emitida em 1 dia); LBI-04 (660 nm, 4,2 J por dia, 16,8 J de energia total emitida em 4 dias); LBI-28, (660 nm, 0,6 J por dia, 16,8 J de energia total emitida durante 28 dias). Os animais foram avaliados utilizando a hiperalgesia térmica, Índice Funcional do Ciático (IFC) e Índice estático do ciático (IEC). Os dados foram obtidos na linha de base e após 7, 14, 21, e 28 dias após a cirurgia. RESULTADOS: Para o IFC e IEC, todos os grupos mostraram um aumento no valor e diferenças significativas em relação ao grupo de controle, e o grupo LBI-04 apresentou os melhores resultados, alcançando valor basal no 21° dia dentre os que foram submetidos a TFBM. Na avaliação da hiperalgesia térmica, houve aumento do tempo de resposta com diferença significativa no 14° dia de avaliação no grupo LBI-04. CONCLUSÃO: A aplicação de 16,8 J foi eficaz na regeneração do nervo ciático quando distribuída ao longo dos 4 primeiros dias pós-lesão, com dose diária de 4,2 J/ponto.

Peripheral nerve entrapments - rare causes of a common condition: case series

Compressive syndromes of peripheral nerves both in the upper and lower limbs are part of daily clinical practice; however, the etiological diagnosis can be challenging and impact on the outcome of the patient. We report five cases with rare etiologies of nerve entrapments: one in the lower limb and four in the upper limbs with the final diagnosis made only during the operation. The patients evolved without post-operative complications and had good outcomes. This series includes the first report of sciatic compression by a lipoma in the popliteal fossa, two lipomas one with compression of infraclavicular brachial plexus and another with compressing the posterior interosseous nerve, and two reports of vascular lesions due to blunt traumas, which are also uncommon. This series adds to the literature more hypotheses of differential diagnoses in nerve entrapments, which is fundamental to surgical decisions and pre-operative planning—and perhaps most importantly prevents wrong diagnosis of idiopathic compressions, which would lead to a completely wrong approach and unfavorable outcomes.

Neuropatía ciática en pediatría: presentación clínica y seguimiento a largo plazo / Pediatric sciatic neuropathy: clinical presentation and long term follow up

Resumen: Introducción: La neuropatía ciática es una entidad infrecuente y de difícil diagnóstico en Pediatría. Su evolución a largo plazo no ha sido claramente definida. Objetivo: Analizar la presentación clínica y evolución de un grupo de niños con neuropatía ciática. Pacientes y Método: Análisis retrospectivo de las características clínicas de pacientes pediátricos con neuropatía ciática atendidos en 2 hospitales de Santiago, entre 2014-2018. Se evaluó examen motor, trofismo muscular, reflejos osteotendíneos, marcha, sensibilidad y dolor. Se estudió neuroconducción de nervio ciático, electromiografía (EMG) y en 3 pacientes, Resonancia Magnética (RM). Resultados: Se incluyeron 6 pacientes, edad promedio 11,8 años. Hubo 2 causas traumáticas, 2 compresivas, 1 vascular y 1 tumoral. Los 6 pa cientes debutaron con pie caído e hiporreflexia/arreflexia aquiliana; 5 pacientes presentaron dolor neuropático severo. La EMG mostró en todos los casos compromiso en nervios y musculatura de pendientes del nervio ciático. En 2 casos se realizó RM de cintura pélvica y extremidades inferiores, mostrando compromiso muscular selectivo en pierna en territorio ciático. En 1 caso, se realizó RM de plexo lumbosacro, y luego estudio histológico, que concluyeron un tumor neural benigno. En los 3 pacientes que tuvieron seguimiento mayor a un año, se observaron secuelas motoras, con marcha alterada. Conclusión: La neuropatía ciática en este grupo fue secundaria a diversas etiologías, predominando las traumático-compresivas. En los 3 casos que tuvieron seguimiento a largo plazo se observaron secuelas motoras significativas. En la mayoría la lesión se asoció a causas prevenibles como accidentes y posicionamiento en niños con compromiso de conciencia, lo que resulta fundamental en la prevención de una patología con alto grado de secuelas.

Abstract: Introduction: Sciatic neuropathy is rare and difficult to diagnose in pediatrics, and its long-term course has not been completely understood. Objective: To analyze the clinical presentation and evolution of a group of pediatric patients with sciatic neuropathy. Patients and Method: Retrospective anal ysis of the clinical characteristics of pediatric patients with sciatic neuropathy treated in two hospitals of Santiago between 2014 and 2018. Locomotor examination, muscle trophism, deep tendon reflexes, gait, sensation, and pain were assessed. Sciatic nerve conduction study and electromyography (EMG) were performed, and magnetic resonance imaging (MRI) in three patients. Results: Six patients were included with an average age of 11.8 years. The etiologies were traumatic (N = 2), by compression (N = 2), vascular (N = 1), and tumor (N = 1). All of the 6 patients presented foot drop and Achilles tendon hyporeflexia/areflexia, and 5 patients presented severe neuropathic pain. The EMG showed involvement of the sciatic nerve rami and dependent muscles. In two patients, a pelvic girdle and lower limbs MRI was performed, showing selective muscle involvement in sciatic territory. One patient underwent a lumbosacral plexus MRI, and subsequently histological study showing a benign neural tumor. Out of the three patients who were followed-up longer than one year presented motor sequelae and gait disorder. Conclusion: Sciatic neuropathy in the study group was secondary to different causes, predominantly traumatic and compressive etiologies. The three patients that were ina long-term follow-up presented significant motor sequelae. In most of the cases, neural injury wasassoci- ated with preventable causes, such as accidents and positioning in unconscious children, which is crucial in the prevention of a pathology with a high sequelae degree.

Analgesic and side effects of intravenous recombinant Ph alfa 1 beta

Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects.

Mechanical properties of the sciatic nerve following combined transplantation of analytically extracted acellular allogeneic nerve and adipose-derived mesenchymal stem cells

Abstract Purpose To investigate the effects of Chemically Extracted Acellular Nerves (CEANs) when combined with Adipose-Derived mesenchymal Stem Cell (ADSC) transplantation on the repair of sciatic nerve defects in rabbits. Methods A total of 71 six-month-old Japanese rabbit were used in this study. Twenty rabbits served as sciatic nerve donors, while the other 51 rabbits were randomly divided into Autologous Nerve Transplantation Group (ANT, n=17), CEAN group (n=17) and CEAN-ADSCs group (n=17). In all these groups, the rabbit's left sciatic nerves were injured before the experiment, and the uninjured sciatic nerves on their right side were used as the control (CON). Electrophysiological tests were carried out and sciatic nerves were prepared for histomorphology and stretch testing at 24 weeks post-transplant. Results There were significant differences between ANT and Con groups in amplitude (AMP): P=0.031; motor nerve conduction velocity (MNCV): P=0.029; Maximum stress: P=0.029; and Maximum strain P=0.027. There were also differences between the CEAN and CEAN+ADSCs groups in AMP: P=0.026, MNCV: P=0.024; Maximum stress: P=0.025 and Maximum strain: P=0.030. No significant differences in these parameters were observed when comparing the ANT and CEAN+SACN groups (MNCV: P=0.071) or the CEAN and ANT groups (Maximum stress: P=0.069; Maximum strain P=0.077). Conclusion Addition of ADSCs has a significant impact on the recovery of nerve function, morphology, and tensile mechanical properties following sciatic nerve injury.

Treatment with ascorbic acid and alpha-tocopherol modulates oxidative-stress markers in the spinal cord of rats with neuropathic pain

Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200-250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group). The vitamins prevented the reduction in total thiol content and the increase in superoxide-anion generation that were found in vehicle-treated CCI rats. While nitric-oxide metabolites increased in vehicle-treated CCI rats 3 days after surgery, these metabolites did not show significant changes in vitamin-treated CCI rats. In all rats, total antioxidant capacity and hydrogen-peroxide levels did not change significantly. Lipid hydroperoxides increased 25% only in vehicle-treated CCI rats. These changes may contribute to vit. C- and vit. E-induced antinociception, because scavenging reactive oxygen species seems to help normalize the spinal cord oxidative status altered by pain.

Analysis of the muscle tissue of Wistar rats submitted to the sciatic nerve compression model and cryotherapy / Análise do tecido muscular de ratos Wistar submetidos ao modelo de compressão do nervo isquiático e à crioterapia

ABSTRACT Objective: To evaluate the effects of right sciatic nerve compression and cryotherapy on muscle tissue. Methods: We used 42 male Wistar rats, subdivided in the following Groups Control, Injury 3, Injury 8 and Injury 15 submitted to nerve compression and euthanized in the 3rd, 8th and 15th day after surgery. The Cryotherapy Injury 3 was entailed treatment with cryotherapy by immersion of the animal in recipient for 20 minutes during 1 day, then animals were euthanized at the 3rd day after surgery, and the Cryotherapy Injury 8 and the Cryotherapy Injury 15 was treated for 6 days, and euthanized at the 8th and 15th day after surgery. Functional evaluation was performed by the grasping strength of the right pelvic limb. The right tibialis anterior muscles were evaluated for mass, smaller diameter and cross-sectional area. In the Cryotherapy Injury 8 and the Cryotherapy Injury 15 groups, the hydroxyproline was dosed in the right soles. Results: In the compression there was a significant difference in the Injury Groups compared with the Control Group (p<0.05). In the smaller diameter, the compression in Control Group was higher than Injury 8 (p=0.0094), Injury 15 (p=0.002) and Cryotherapy Injury 15 (p<0.001) groups. The comparison between groups with euthanasia in the same post-operative period, a significant difference (p=0.0363) was seen in day 8th after surgery, and this result in Cryotherapy Injury Group was greater than Injury Group. In the fiber area, Control Group was also higher than the Injury 8 (p=0.0018), the Injury 15 (p<0.001) and the Cryotherapy Injury 15 (p<0.001). In hydroxyproline, no significant difference was seen between groups. Conclusion: Nerve damage resulted in decreased muscle strength and trophism, the cryotherapy delayed hypotrophy, but this effect did not persist after cessation of treatment.

RESUMO Objetivo: Avaliar os efeitos da compressão nervosa do isquiático direito e da crioterapia no tecido muscular. Métodos: Foram utilizados 42 ratos Wistar machos, subdivididos nos Grupos Controle, Lesão 3, Lesão 8 e Lesão 15, submetidos a compressão nervosa e eutanasiados, respectivamente, no 3°, 8° e 15° dias pós-operatório; Lesão Crioterapia 3, tratado com crioterapia, por imersão durante 20 minutos, por 1 dia, e eutanasiados no 3° dia pós-operatório; e Lesão Crioterapia 8 e Lesão Crioterapia 15, tratados durante 6 dias e eutanasiados no 8° e 15° dias pós-operatório. A avaliação funcional foi realizada pela força de preensão do membro pélvico direito. Os músculos tibiais anteriores direitos foram avaliados quanto a massa, menor diâmetro e área de secção transversa. Em Lesão Crioterapia 8 e Lesão Crioterapia 15, foi dosada a hidroxiprolina nos sóleos direitos. Resultados: Na preensão, houve diferença significativa nos Grupos Lesão quando comparados ao Grupo Controle (p<0,05). No menor diâmetro, o Grupo Controle foi maior que Lesão 8 (p=0,0094), Lesão 15 (p = 0,002) e Lesão Crioterapia 15 (p<0,001). Na comparação entre os grupos com eutanásia no mesmo pós-operatório, houve diferença significativa (p=0,0363) no 8° pós-operatório, sendo Lesão Crioterapia maior que Lesão. Na área das fibras, o Grupo Controle também foi maior que Lesão 8 (p=0,0018), Lesão 15 (p<0,001) e Lesão Crioterapia 15 (p<0,001). Na hidroxiprolina, não houve diferença significativa entre os grupos. Conclusão: A lesão nervosa resultou na diminuição da força e em trofismo muscular, e a crioterapia retardou a hipotrofia, porém este efeito não se manteve após o tratamento cessar.

Action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after nerve injury / Ação da vanilina (Vanilla planifolia) sobre a morfologia dos músculos tibial anterior e sóleo após lesão nervosa

ABSTRACT Objective To evaluate the action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after peripheral nerve injury. Methods Wistar rats were divided into four groups, with seven animals each: Control Group, Vanillin Group, Injury Group, and Injury + Vanillin Group. The Injury Group and the Injury + Vanillin Group animals were submitted to nerve injury by compression of the sciatic nerve; the Vanillin Group and Injury + Vanillin Group, were treated daily with oral doses of vanillin (150mg/kg) from the 3rd to the 21st day after induction of nerve injury. At the end of the experiment, the tibialis anterior and soleus muscles were dissected and processed for light microscopy and submitted to morphological analysis. Results The nerve compression promoted morphological changes, typical of denervation, and the treatment with vanillin was responsible for different responses in the studied muscles. For the tibialis anterior, there was an increase in the number of satellite cells, central nuclei and fiber atrophy, as well as fascicular disorganization. In the soleus, only increased vascularization was observed, with no exacerbation of the morphological alterations in the fibers. Conclusion The treatment with vanillin promoted increase in intramuscular vascularization for the muscles studied, with pro-inflammatory potential for tibialis anterior, but not for soleus muscle.

RESUMO Objetivo Avaliar a ação da vanilina (Vanilla planifolia) sobre a morfologia dos músculos tibial anterior e sóleo após lesão nervosa periférica. Métodos Ratos Wistar foram divididos em quatro grupos, com sete animais cada, sendo Grupo Controle, Grupo Vanilina, Grupo Lesão e Grupo Lesão + Vanilina. Os animais dos Grupos Lesão e Grupo Lesão + Vanilina foram submetidos à lesão nervosa por meio da compressão do nervo isquiático, e os Grupos Vanilina e Grupo Lesão + Vanilina foram tratados diariamente com doses orais de vanilina (150mg/kg) do 3o ao 21o dia após a indução da lesão nervosa. Ao término do experimento, os músculos tibial anterior e sóleo foram dissecados e seguiram o processamento de rotina em microscopia de luz, para posterior análise morfológica. Resultados A compressão nervosa promoveu alterações morfológicas características de denervação, sendo que o tratamento com vanilina foi responsável por respostas distintas nos músculos estudados. Para o tibial anterior, houve aumento do número de células satélites, núcleos centrais e atrofia das fibras, bem como desorganização fascicular. Já no sóleo, houve apenas aumento da vascularização, sem exacerbação das alterações morfológicas nas fibras. Conclusão O tratamento com vanilina promoveu o aumento da vascularização intramuscular para os músculos estudados, com potencial pró-inflamatório para o tibial anterior, o que não ocorreu no músculo sóleo.

Jumping in aquatic environment after sciatic nerve compression: nociceptive evaluation and morphological characteristics of the soleus muscle of Wistar rats / Salto em meio aquático após compressão de nervo isquiático: avaliação nociceptiva e características morfológicas do músculo sóleo de ratos Wistar

ABSTRACT Objective To evaluate the effect of jumping in aquatic environment on nociception and in the soleus muscle of trained and not trained Wistar rats, in the treatment of compressive neuropathy of the sciatic nerve. Methods Twenty-five Wistar rats were distributed into five groups: Control, Lesion, Trained + Lesion, Lesion + Exercise, and Trained + Lesion + Exercise. The training was jumping exercise in water environment for 20 days prior to injury, and treatment after the injury. Nociception was evaluated in two occasions, before injury and seven after injury. On the last day of the experiment, the right soleus muscles were collected, processed and analyzed as to morphology and morphometry. Results In the assessment of nociception in the injury site, the Control Group had higher average than the rest, and the Lesion Group was larger than the Trained + Lesion and Lesion + Exercise Groups. The Control Group showed higher nociceptive threshold in paw, compared to the others. In the morphometric analysis, in relation to Control Group, all the injured groups showed decreased muscle fiber area, and in the Lesion Group was lower than in the Lesion + Exercise Group and Trained + Lesion Group. Considering the diameter of the muscle fiber, the Control Group had a higher average than the Trained + Lesion Group and the Trained + Lesion + Exercise Group; and the Lesion Group showed an average lower than the Trained + Lesion and Lesion + Exercise Groups. Conclusion Resistance exercise produced increased nociception. When performed prior or after nerve damage, it proved effective in avoiding hypotrophy. The combination of the two protocols led to decrease in diameter and area of the muscle fiber.

RESUMO Objetivo Avaliar os efeitos do salto em meio aquático, na nocicepção e no músculo sóleo, em ratos Wistar treinados e não treinados, no tratamento de neuropatia compressiva do nervo isquiático. Métodos Foram distribuídos em cinco grupos 25 ratos Wistar: Controle, Lesão, Treinado + Lesão, Lesão + Exercício e Treinado + Lesão + Exercício. O treino foi com exercício de salto em meio aquático durante 20 dias, prévio à lesão, e o tratamento ocorreu após a lesão. Foram realizadas avaliações da nocicepção, sendo uma pré-lesão e sete pós-lesão. No último dia de experimento, os músculos sóleos direitos foram coletados, processados e analisados por meio de morfologia e morfometria. Resultados Na avaliação da nocicepção no local da lesão, o Grupo Controle apresentou média maior que os demais, e o Grupo Lesão foi maior que os Grupos Treinado + Lesão e Lesão + Exercício. O Grupo Controle apresentou limiar nociceptivo na pata maior com relação aos demais. Nas análises morfométricas, em relação ao Grupo Controle, todos os grupos lesionados apresentaram diminuição da área da fibra muscular; o Grupo Lesão apresentou-se menor que os Grupos Treinado + Lesão e Lesão + Exercício. No diâmetro da fibra muscular, o Grupo Controle apresentou média maior que os Grupos Treinado + Lesão e Treinado + Lesão + Exercício, e o Grupo Lesão apresentou média menor que os Grupos Treinado + Lesão e Lesão + Exercício. Conclusão O exercício físico resistido produziu aumento da nocicepção. Quando realizado previamente ou após a lesão nervosa, mostrou-se eficaz em evitar a hipotrofia. A associação dos dois protocolos levou à diminuição do diâmetro e da área da fibra muscular.

Ação do exercício de subida em escada com sobrecarga na morfologia do músculo tibial anterior de ratos Wistars após axonotmese / Action of the climbing ladder exercise with overload in the morphology of the anterior tibial muscle of wistars rats after axonotmesis

Objetivo: avaliar histomorfometrica e morfologicamente o músculo tibial anterior de ratos submetidos à axonotmese e tratados com exercício. Métodos: foram randomizados 28 ratos Wistar nos grupos controle (GC), exercício (GE), lesão (GL) e lesão+exercício (GLE). No terceiro dia após compressão, GE e GLE realizaram exercício de subida em escada, com duas séries de dez repetições. Após 21 dias, o músculo tibial anterior foi processado para microscopia de luz. Resultados: Na análise morfológica GC apresentou morfologia com aspecto característico, GE hipertrofia muscular, GL alterações morfológicas, como fibras polimórficas e núcleos centrais, e GLE aspecto semelhante ao controle, porém com algumas alterações. Na área de secção transversa e menor diâmetro das fibras GC e GE apresentaram valores maiores, o inverso da análise de vasos sanguíneos. Para o tecido conjuntivo, GE apresentou-se menor que o GL. Conclusão: O protocolo de exercício promoveu melhora nos aspectos histomorfológicos, mas não reverteu totalmente os efeitos deletérios. (AU)

Objective: to evaluate morphologically the tibialis anterior muscle of rats submitted to axonotmosis and treated with exercise. Methods: 28 Wistar rats were used in groups control (CG), exercise (GE), injury (GL) and injury + exercise (GLE). On the third day after compression, GE and GLE performed climb exercise staircase, with two sets of ten repetitions. After 21 days, the muscle was processed for light microscopy. Results: In the morphological analysis GC presented with morphology characteristic appearance, GE muscle hypertrophy, GL morphological changes like polymorphic fibers and central nucleo, and GLE look similar to the control, but with some changes morphological. In the cross-sectional area and smaller diameter of the GC and GE fiber showed higher values, inversed analysis of blood vessels. For the connective tissue, GE was lower than the GL. Conclusion: Summing up, the exercise promoted improvement in morphological aspects, but not totally reversed the deleterious effects of denervation. (AU)

Effects of N-acetylcysteine on spinal cord oxidative stress biomarkers in rats with neuropathic pain

N-acetylcysteine (NAC) inhibits nociceptive transmission. This effect has been associated partly with its antioxidant properties. However, the effect of NAC on the levels of lipid hydroperoxides (a pro-oxidant marker), content of ascorbic acid (a key antioxidant molecule of nervous tissue) and total antioxidant capacity (TAC) is unknown. Thus, our study assessed these parameters in the lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, one of the most commonly employed animal models of neuropathic pain. Thirty-six male Wistar rats weighing 200-300 g were equally divided into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve). All rats received intraperitoneal injections of NAC (150 mg·kg−1·day−1) or saline for 1, 3, or 7 days. Rats were killed 1, 3, and 7 days after surgery. NAC treatment prevented the CCI-induced increase in lipid hydroperoxide levels only at day 1, although the amount was higher than that found in naive rats. NAC treatment also prevented the CCI-induced increase in ascorbic acid content, which occurred at days 1, 3, and 7. No significant change was found in TAC with NAC treatment. The changes observed here may be related to the antinociceptive effect of NAC because modulation of oxidative-stress parameters seemed to help normalize the spinal cord oxidative status altered by pain.

Efeito do exercício resistido na redução do edema, nocicepção e regeneração nervosa em um modelo de compressão do nervo isquiático / Effect of resistance training on the reduction of edema, nociception, and nerve regeneration in a sciatic nerve compression model

OBJETIVOS: Analisar os efeitos do exercício físico resistido de subida em escada, sobre o edema, nocicepção e regeneração nervosa de ratos Wistar, submetidos à compressão do nervo isquiático. MÉTODOS: Foram estudados 24 ratos Wistar, divididos igualmente entre quatro grupos: Grupo Controle, Grupo Exercício, Grupo Lesão e Grupo Tratado ­ Lesão e Exercício. O Grupo Lesão e o Grupo Tratado foram submetidos à compressão do nervo isquiático com pinça hemostática por 30 segundos. A partir do terceiro dia após a lesão, iniciou-se o tratamento com exercício resistido de subida em escada para o Grupo Exercício e o Grupo Tratado. O tratamento consistiu em realizar duas séries de 10 subidas na escada, com sobrecarga de 100 gramas e intervalo de um minuto entre uma série e outra. O estudo foi conduzido por 22 dias e nesse tempo os animais foram avaliados quanto ao edema e à nocicepção. No 22º dia de pós-operatório, os animais foram anestesiados para retirada de um fragmento do nervo isquiático para análise do número de axônios e da densidade de fibras. Em seguida, ainda sob efeito da anestesia, os animais foram eutanasiados. Os nervos coletados seguiram protocolo de processamento histológico de rotina. As expressões do Fator de Crescimento Neural e do Fator de Crescimento Derivado do Cérebro foram avaliadas por Western blotting. RESULTADOS: Não houve diferença significativa entre os grupos no tamanho do edema. O Grupo Controle apresentou maior limiar nociceptivo comparado aos demais grupos. A análise morfométrica não revelou diferença significativa entre os grupos, quanto à quantidade de axônios e à densidade de fibras. A expressão do Fator de Crescimento Derivado do Cérebro foi maior no Grupo Lesão e no Grupo Tratado quando comparados ao Grupo Controle. CONCLUSÕES: O exercício físico resistido de subida em escada, nos parâmetros propostos, não foi eficaz para reduzir o edema, a nocicepção ou aumentar o número de axônios e a densidade de fibras nervosas após lesão do nervo isquiático.

AIMS: To analyze the effects of ladder-climbing resistance training exercise on edema, nociception, and regeneration of the sciatic nerve in Wistar rats subjected to sciatic nerve compression. METHODS: Twenty-four Wistar rats were divided into four groups: Control Group, Exercise Group, Injury Group, and Treated Group (injury and exercise). Injury Group and Treated Group were subjected to sciatic nerve compression with a hemostat for 30 seconds. On the third day after injury, Exercise Group and Treated Group began treatment with ladder-climbing resistance exercise. The treatment consisted in performing two series of 10 ladder climbs with a 100-gram overload and a one-minute interval between the series. The study was conducted for 22 days, during which time the animals were evaluated for edema and nociception. Twenty-two days after surgery, the animals were anesthetized for removal of a sciatic nerve fragment and analysis of the number of axons and fiber density. Thereafter, still under anesthesia, the animals were euthanized. Nerve sampling followed the routine histological processing protocol. Expressions of Neural Growth Factor and Brain-derived Neurotrophic Factor were evaluated by Western blotting. RESULTS: There was no significant difference in edema size between groups. Control Group showed the highest nociceptive threshold compared to the other groups. The morphometric analysis showed no significant difference in number of axons and fiber density between groups. The expression of Brain-derived Neurotrophic Factor was greater in the Injury Group and the Treated Group compared to the Control Group. CONCLUSIONS: The proposed ladder-climbing resistance training was not effective in reducing edema and nociception or in increasing the number of axons and fiber density after sciatic nerve injury.

Schwannomas of Peripheral Nerves: Unusual Cause of Sciatic and Literature Review / Schwanomas dos nervos periféricos: causa rara de ciatalgia e revisão da literatura

Schwannomas of peripheral nerves are the most common benign tumors in this location; it has specific radiologic and histologic features that enable its fundamental distinction of neurofibromas. Given its importance in neurosurgical practice, known radiologic and histologic criteria must be updated regarding this disease entity, as well as its therapeutic strategy and results obtained with it. This article reviews this subject, followed by a case report considered out of the ordinary, in which the tumor was located in the sciatic nerve in a patient with neurofibromatosis type 1, treated by microsurgical resection, which evolved favorably.

Os schwannomas dos nervos periféricos são os tumores benignos mais comuns nesta localização. Apresentam características radiológicas e histológicas específicas que possibilitam a sua fundamental distinção dos neurofibromas. Dada a sua importância na prática neurocirúrgica, devem ser conhecidos os critérios radiológicos e histológicos atualizados à respeito desta entidade nosológica, bem como sua estratégia terapêutica e o resultado com ela obtido. Neste artigo, é feita uma revisão do tema, seguido do relato de um caso considerado fora do habitual, no qual o tumor localizava-se no nervo ciático, em uma paciente portadora de neurofibromatose tipo 1, tratada por meio de ressecção microcirúrgica, que evoluiu de forma favorável.

Lombociatalgia, um desafio na prática clínica / Sciatalgia, a challenge in clinical practice

A lombociatalgia afeta uma proporção significativa da população, sendo uma das principais queixas no consultório médico. O termo ciatalgia pode causar confusão, já que tem sido usado para descrever qualquer dor, incluindo dor referida, sentida na distribuição do nervo ciático na perna. Neste contexto, cabe ao estudo revisar a correta avaliação e o tratamento da dor ciática verdadeira.

Low back pain affects a significant proportion of the population; being one of the most common pain reports in the medical office. The term ciatic neuralgia can cause confusion as it has been used to define any pain, including referred, felt in the leg along the sciatic nerve. In this context, this study will review the correct way to evaluate and treat the true sciatica.

Atrapamiento del nervio ciático en el espacio subglúteo: tratamiento endoscópico / Deep gluteal syndrome. Endoscopic treatment

Se ha sugerido el término síndrome de glúteo profundo (deep gluteal syndrome) (SGP) para definir la compresión del nervio ciático en la región anatómica del espacio glúteo, o aquellas ciáticas no discogénicas con origen en esta región. Este síndrome tiene una alta prevalencia pero un bajo diagnóstico. Existen numerosas causas que pueden originar su afectación y compresión a nivel de dicho espacio. El uso rutinario de los test de evaluación, junto con una sospecha diagnóstica, determinará la incidencia real de este síndrome. La cirugía abierta ha sido descripta y utilizada como tratamiento. El tratamiento endoscópico es efectivo y disminuye el índice de morbilidad y eficacia en comparación con la cirugía abierta. El objetivo del trabajo es presentar una actualización de las características clínicas, test diagnósticos, métodos complementarios, causas y alternativas de tratamiento del SGP, haciendo hincapié en los detalles técnicos del procedimiento endoscópico.

The term Deep Gluteal Syndrome (DGS) has been suggested to define the compression of the sciatic nerve in the anatomical region of the gluteal space, or those ciatic non-discogenic pain with origin in this region. Pathology that is presented with a high prevalence, but at the moment underdiagnosed. There are numerous causes that can originate their affectation and compression at level of this space. The routine use of the evaluation test, together with a diagnostic suspicion, it will determine the real incidence of this problem. The open surgery has been described and used as treatment. The endoscopic treatment is effective and adds less morbidity and effectiveness in comparison with the open surgery. The objective of this article is to present an upgrade of the clinical features, diagnostic test, complementary methods, causes and alternative of treatment of the DGS, making stress in the surgical technique of the endoscopic release.

Varizes do nervo ciático são uma doença pouco conhecida? / Nerve varices a little known disease?

Objetivo: Relatar nossa experiência com varizes do nervo ciático e indicar que tipo de paciente é mais provável de ser acometido por essa patologia. Método: A amostra foi constituída de 2.400 pacientes, selecionando-se 80 deles (3,3%) como possíveis portadores de varizes do nervo ciático. Foram considerados pacientes suspeitos: pacientes portadores de varizes na face lateral da perna, coxa e oco poplíteo; pacientes com recidiva anárquica de varizes após safenectomia; pacientes com sintomas e exames positivos para varizes pélvicas; pacientes com história prévia de trombose venosa profunda; pacientes com queixas de dores ciáticas e aumento do diâmetro de um membro com relação ao outro. Esses pacientes foram submetidos a exames detalhados e rigorosos do losango poplíteo com objetivo de identificar varizes dentro da bainha do nervo ciático e na face lateral da perna. Desses, 10 foram submetidos à angiografia venosa para detalhar a relação anatômica com o nervo ciático. Resultados: De 80 pacientes previamente selecionados, encontramos 21 (26,3%) casos positivos para varizes do nervo ciático ao exame ecográfico. Dez pacientes tinham varizes do nervo ciático associadas a recidiva anárquica de varizes após safenectomia e outros 10 associadas a varizes pélvicas. A dor ciática esteve presente em 100% dos pacientes positivos para VNC. Conclusão: Varizes do nervo ciático são pouco conhecidas pela medicina. Se o médico fizer uma seleção prévia conforme descrito em ?pacientes e métodos? e concentrar-se no exame ecográfico do losango poplíteo e face lateral da perna, irá se surpreender com o elevado número de casos de varizes do nervo ciático que diagnosticará.

Objective: To report our experience with patients with sciatic nerve varices (SNV) and to indicate which type of patient is more likely to be afflicted with this particular pathology. Method: The sample consisted of 2,400 patients, selecting 80 (3.3%) as possible sufferers of SNV. Patients with the following conditions were highly suspected: patients with varices on the lateral aspect of the leg, the thigh, and oco politeo; patients with uncontrolled variceal recurrence after a safenectomy; patients with symptoms of and who tested positive for pelvic varices; patients with a history of deep vein thrombosis; and patients complaining of sciatic pain along with an increase in the diameter of one limb in relation to the other. These patients underwent detailed and rigorous examination of the ?losango popliteo? with the objective of identifying varices inside the sheath of the sciatic nerve and on the lateral aspect of the leg. Of these, 10 underwent venous angiography to detail the anatomical relationship with the sciatic nerve. Results: Of the 80 patients previously selected, we found 21 (26.3%) cases that were positive for SNV through ultrasound. Ten patients had SNV associated with uncontrolled variceal recurrence after safenectomy, while the other 10 were associated with pelvic varices. Sciatic pain was present in 100% of the patients who tested positive for SNV. Conclusion: SNV are not well known in Medicine. If the doctor makes a examination as described in the ?patients and methods? section and concentrates on the ultrasound scan of the ?diamond popliteal? and lateral aspect of the leg, he or she will be surprised by the high number of cases of SNV that will be diagnosed.

Estimulação elétrica de alta voltagem em nervo ciático de ratos: estudo pelo IFC / High voltage pulsed current stimulation of the sciatic nerve in rats: analysis by the SFI

OBJETIVO: Analisar a eficiência do tratamento com a estimulação elétrica de alta voltagem (EEAV) em três diferentes locais, aplicada precocemente na regeneração do nervo ciático submetido à lesão por esmagamento, e avaliada através do índice funcional do ciático (IFC), em ratos. MÉTODO: Após o esmagamento, 57 ratos foram submetidos à EEAV catódica nos parâmetros: frequência de 50Hz, 100V de tensão, 20 minutos diários, 5 dias por semana. Os ratos foram divididos aleatoriamente em: grupo controle; grupo gânglio; grupo gânglio + músculo; grupo músculo e; grupo simulado. O IFC foi avaliado semanalmente durante sete semanas, partindo do pré-operatório até a 6ª semana pós-operatória. RESULTADOS: Em comparação ao grupo controle, os resultados mostraram desempenho significativamente superior do grupo gânglio nas três primeiras semanas, e do grupo gânglio + músculo na 3ª semana, enquanto o grupo músculo teve desempenho significativamente negativo na 4ª e 6ª semanas. CONCLUSÃO: a EEAV aplicada precocemente, foi positiva no tratamento da região da medula e gânglio da raiz nervosa do ciático com o eletrodo dispersivo na região lombar contralateral ou no músculo gastrocnêmio. Porém, proporcionou efeitos negativos no tratamento com eletrodo ativo no músculo gastrocnêmio e dispersivo na coxa contralateral. Nível de evidência II, Estudo prospectivo comparativo.

OBJECTIVE: To analyze the efficiency of high voltage pulsed current (HVPC) with early application in three different sites, in the regeneration of the sciatic nerve in rats submitted to crush injury, the sciatic functional index (SFI) was used to assess the functional recovery. METHODS: After crushing of the nerve, 57 animals were submitted to cathodal HVPC at frequency of 50Hz and voltage of 100V, 20 minutes per day, 5 days per week. The rats were divided into five groups: control group; ganglion group; ganglion + muscle group; muscle group; and sham group. The SFI was determined weekly for seven weeks, from the preoperative period to the 6th postoperative week. RESULTS: Compared with the control group, the results showed a significantly better performance of group 2 for the first 3 weeks; group 3 showed significantly better performance in the third week; and group 4 showed a significantly negative performance during the 4th and 6th weeks. CONCLUSION: Early application of HVPC had a positive effect in the treatment of the spinal cord region and the sciatic nerve root ganglion with a dispersive electrode on the contralateral lumbar region or on the gastrocnemius. However, HVPC had a negative effect in the treatment with an active electrode on the gastrocnemius and a dispersive electrode on the contralateral thigh. Level of evidence II, Prospective comparative study.