Drug repositioning: diacerein as a new therapeutic approach in a mice model of sciatic nerve injury.

BACKGROUND: Peripheral nerve injuries negatively impact the quality of life of patients, with no effective treatment available that accelerates sensorimotor recovery and promotes functional improvement and pain relief. The aim of this study was to evaluate the effects of diacerein (DIA) in an experimental mice model of sciatic nerve crush. METHOD: In this study, male Swiss mice were used, randomly separated into six groups as follows: FO (false-operated + vehicle); FO + DIA (false-operated + diacerein 30 mg/kg); SNI (sciatic nerve injury + vehicle); SNI + DIA in doses of 3, 10 and 30 mg/kg (sciatic nerve injury + treatment with diacerein in doses of 3-30 mg/kg). DIA or vehicle was administered 24 h after the surgical procedure, intragastrically, twice a day. The lesion of the right sciatic nerve was generated by crush. RESULTS: We found that the treatment of animals with DIA accelerated sensorimotor recovery of the animal. In addition, animals in the sciatic nerve injury + vehicle (SNI) group showed hopelessness, anhedonia, and lack of well-being, which were significantly inhibited by DIA treatment. The SNI group showed a reduction in the diameters of nerve fibers, axons, and myelin sheaths, while DIA treatment recovered all these parameters. In addition, the treatment of animals with DIA prevented an increase the levels of interleukin (IL)-1ß and a reduction in the levels of the brain-derived growth factor (BDNF). CONCLUSIONS: Treatment with DIA reduces hypersensitivity and depression like behaviors in animals. Furthermore, DIA promotes functional recovery and regulates IL-1ß and BDNF concentrations.

The Antinociceptive Effect of a Hydroalcoholic Extract of Polygala altomontana and Its Chemical Profile Using UPLC-ESI-QTOF-HR-MS.

The hydroalcoholic extract of Polygala altomontana (30, 100, and 300 mg/kg, i.g.) showed a dose-dependent antinociceptive action during the inflammatory phase of the formalin test. In addition, the preparation (30 and 300 mg/kg, i.g.) showed anti-hyperalgesic action when tested on a mechanical nociception model. UPLC-ESI-QTOF-MS data indicated the active extract contained phenylpropanoid sucrose esters, glycosylated quercetin derivatives, styrylpyrones, and coumarins. Some identified compounds, including styrylpyrones and coumarins, have previously demonstrated antinociceptive action. The results also show that P. altomontana shows potential for developing pain-relieving herbal remedies and drugs.

The antinociceptive effect of manual acupuncture in the auricular branch of the vagus nerve in visceral and somatic acute pain models and its laterality dependence.

AIMS: The vagus nerve provides an important route to the central nervous system, and its brain projections are involved in nociceptive control and pain perception. We investigated the effect of ABVN stimulation on the inhibition of nociceptive signaling and the role of the cholinergic system in its neurobiological effects in models of visceral-somatic pain in rats, as well as the potential difference in stimulus laterality. MATERIALS AND METHODS: Male and female Wistar rats were pretreated with auricular acupuncture in the ABVN and submitted to the visceral-somatic nociception model by acetic acid or somatic nociception by formalin. Vagotomy and pharmacological tools were used to verify the participation of the cholinergic system in the experiments. KEY FINDINGS: Acupuncture on the left, but not the right, in the ABVN inhibited nociceptive signaling in the visceral-somatic nociception model in male and female rats. Acupuncture on the left ABVN reduced the response time in the formalin test. The cervical vagotomy of the left branch, but not the right, also inhibited nociceptive signaling in the visceral-somatic nociception model and reduced the effect of ABVN stimulation. Furthermore, cholinergic antagonists reduced the left ABVN stimulation effects in the same model. SIGNIFICANCE: Our data show that only the stimulation in the left ABVN is capable of producing antinociceptive effect in acute pain models in rats, and that it is dependent on the activation of the vagus nerve caudal to the nodose ganglion, as well as the muscarinic and nicotinic cholinergic receptors.

Analysis of the muscle tissue of Wistar rats submitted to the sciatic nerve compression model and cryotherapy.

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.

Crioterapia em modelo de compressão do nervo isquiático: análise funcional e morfológica / Cryotherapy in sciatic nerve compression model: functional and morphological analysis / Crioterapia en modelo de compresión del nervio ciático: análisis funcional y morfológico

RESUMO Introdução: A crioterapia é uma modalidade terapêutica que visa reduzir processos álgicos e inflamatórios, sendo que a imersão é considerada a forma mais eficaz; no entanto, a literatura apresenta possíveis efeitos deletérios com relação à aplicação da crioterapia em nervos superficiais. Objetivo: Avaliar o efeito da crioterapia em modelo experimental de compressão do nervo isquiático em ratos Wistar, por meio de análise funcional e morfológica. Métodos: Foram utilizados 42 ratos, sendo seis animais por grupo: G1 - controle, submetido à eutanásia no 15º dia de pós-operatório (PO); G2, G3 e G4 - submetidos à compressão do nervo isquiático, submetidos à eutanásia no 3º, 8º e 15º dias de PO, respectivamente; G5, G6 e G7 - submetidos à compressão do nervo isquiático e tratados com crioterapia, submetidos à eutanásia no 3º, 8º e 15º dias de PO, respectivamente. As avaliações do índice funcional do isquiático (IFC) e do teste de incapacidade funcional aconteceram nos momentos pré-lesão, no 2º de PO e no dia da eutanásia em cada grupo com lesão. Após o período de intervenção, os animais foram devidamente anestesiados e o nervo isquiático distal ao procedimento de compressão foi dissecado e coletado para análise morfológica. A análise estatística foi realizada pelo teste de ANOVA mista, com nível de significância de 5%. Resultados: Houve diminuição do IFC após a lesão e o teste de incapacidade funcional mostrou aumento do tempo de elevação da pata. Com relação à análise morfológica, o G1 apresentou fibras nervosas com aspecto normal e nos grupos com lesão houve degeneração nervosa, sendo que o G6 teve uma discreta recuperação das fibras nervosas, além de leve regeneração no G4 e G7. Conclusão: A crioterapia não foi eficaz para recuperar os parâmetros funcionais analisados, entretanto, houve discreta melhora dos aspectos morfológicos do grupo submetido à eutanásia no 8º dia de PO. Nível de Evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

ABSTRACT Introduction: Cryotherapy is a therapeutic modality that aims to reduce inflammatory and painful processes, with immersion being considered the most effective form; however, the literature has possible deleterious effects related to the application of cryotherapy to superficial nerves. Objective: To evaluate the effect of cryotherapy in experimental model of sciatic nerve compression in Wistar rats, through morphologic and functional analysis. Methods: Forty-two rats were used, six animals per group: G1 - control euthanized on the 15th postoperative day (PO); G2, G3 and G4 - submitted to sciatic nerve compression, euthanized at 3rd, 8th and 15th PO days, respectively; G5, G6 and G7 - submitted to sciatic nerve compression and treated with cryotherapy, euthanized at 3rd, 8th and 15th PO days, respectively. The assessments of sciatic functional index (SFI) and the functional disability test took place at the pre-injury, 2nd PO and on the day of euthanasia in each group with injury. After the intervention period, the animals were anesthetized properly and the sciatic nerve distal to the compression procedure was dissected and collected for morphological analysis. Statistical analysis was by the mixed ANOVA test with a significance level of 5%. Results: There was a decrease of SFI after injury and the functional disability test showed an increase in paw elevation time. Regarding the morphological analysis, the G1 showed normal nerve fibers and in the groups with lesion, there was nerve degeneration, G6 had a slight recovery of the nerve fibers, besides mild regeneration in G4 and G7. Conclusion: Cryotherapy was not effective to recover the functional parameters analyzed; however, there was a slight improvement in the morphological aspects of the group euthanized on the 8th PO day. Level of Evidence II; Therapeutic studies - Investigating the results of treatment.

RESUMEN Introducción: La crioterapia es una modalidad terapéutica que busca reducir procesos de dolor e inflamatorios, siendo que la inmersión es considerada la forma más eficaz; sin embargo, la literatura presenta posibles efectos deletéreos con relación a la aplicación de la crioterapia en nervios superficiales. Objetivo: Evaluar el efecto de la crioterapia en modelo experimental de compresión del nervio ciático en ratas Wistar, por medio de análisis funcional y morfológico. Métodos: Se utilizaron 42 ratas, siendo seis animales por grupo: G1 - control, sometido a la eutanasia en el 15º día de postoperatorio (PO); G2, G3 y G4 - sometidos a la compresión del nervio ciático, sometidos a la eutanasia en los 3º, 8º y 15º días de PO, respectivamente; G5, G6 y G7 - sometidos a la compresión del nervio ciático y tratados con crioterapia, sometidos a la eutanasia en los 3º, 8º y 15º días de PO, respectivamente. Las evaluaciones del índice funcional del ciático (IFC) y la prueba de incapacidad funcional ocurrieron en los momentos pre-lesión, en el 2º día de PO y el día de la eutanasia en cada grupo con lesión. Después del período de intervención, los animales fueron debidamente anestesiados y el nervio ciático distal al procedimiento de compresión fue disecado y recogido para análisis morfológico. El análisis estadístico fue realizado por la prueba de ANOVA mixta, con un nivel de significancia del 5%. Resultados: Hubo disminución del IFC después de la lesión y la prueba de incapacidad funcional mostró aumento del tiempo de elevación de la pata. En cuanto al análisis morfológico, el G1 presentó fibras nerviosas con aspecto normal y en los grupos lesionados hubo degeneración nerviosa, siendo que el G6 tuvo una discreta recuperación de las fibras nerviosas, además de ligera regeneración en el G4 y G7. Conclusión: La crioterapia no fue eficaz para recuperar los parámetros funcionales analizados, sin embargo, hubo discreta mejora de los aspectos morfológicos del grupo sometido a la eutanasia en el 8º día de PO. Nivel de Evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamento.

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.

Therapeutic ultrasound after sciatic nerve compression of Wistar rats.

OBJECTIVES: The present study analyzed the effect of therapy with therapeutic ultrasound on the sciatic nerve after compression injury, comparing two similar doses of SATA. METHODS: In total, 32 Wistar rats were used, divided into the following groups: CG - control; IG - compression injury of the sciatic nerve; IGCU - injury and continuous ultrasound; and IGPU - injury and 20% pulsed ultrasound. The treatment with ultrasound started on the 3rd postoperative day, with a frequency of 1 MHz, 0.4 W/cm² (SATA) for IGCU. IGPU received 2.0 W/cm2 (SATP), with 20% of the active cycle, for 3 minutes. The treatment was performed on a daily basis, totaling 15 days of therapy. Evaluations were performed for functional, histological, and morphometric forms. RESULTS: Both the Sciatic Functional Index and the withdrawal threshold and grip strength failed to show an advantage of using therapeutic ultrasound. For the morphometric evaluations of nerve fiber diameter and axons, myelin sheath thickness, and G quotient and nerve fiber estimates, IGPU values were estimated to be significantly lower. The morphological analysis revealed intense inflammatory response and neovascularization, as well as degeneration of axons and the myelin sheath, for the injury group and IGCU; however, IGPU showed greater tissue disorganization. CONCLUSION: There were no significant differences, showing functional or nocicepitive recovery of the treated groups, including with characteristics pointing to the pulsed group with worse results.

Jumping in aquatic environment after sciatic nerve compression: nociceptive evaluation and morphological characteristics of the soleus muscle of Wistar rats.

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. 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)

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.

Effects of the platelet-rich fibrin associated with physical exercise in a model of median nerve compression

AIMS: Platelet-Rich Fibrin (PRF) is a new and promising technique for tissue repair, however, there is still a gap about its action on peripheral nerve injury, as well as its association with physical exercise. Thus, the aim of this study was to evaluate the effects of the PRF associated with physical exercise in a model of median nerve compression. METHODS: 42 rats, divided into: Control, non-injured limb, and other six groups with nerve lesion (Control lesion; Treated with PRF; Treadmill walking; Free swimming; PRF and treadmill; PRF and swimming). The lesion model was performed with median nerve compression. To obtain the PRF, 1.5 mL of blood was centrifuged and the fibrin clot positioned directly over the compression region. The exercise protocols were performed during 2 weeks. The evaluations performed were grip strength tests and histologic analysis. RESULTS: both, grip strength and histomorphometric evaluations (fiber numbers and axon density) did not present significant differences between the treated and lesion groups, however, in the morphological evaluation it was possible to distinguish characteristics of the repair process for the treated groups. CONCLUSION: a slight qualitative improvement was observed for the treated groups, especially when it was associated PRF with free swimming.(AU)

Proprioceptive evaluation in healthy women undergoing Infrared Low Level Laser Therapy

Abstract Aim To evaluate if the application of infrared low-level laser therapy (LLLT) alters proprioception in young women. Methods 26 female volunteers were evaluated statically and dynamically by means of electronic baropodometry in the variables: distance from the foot center, maximum and medium pressure, and surface. Proprioception was also functionally assessed by the Star Excursion Balance Test (SEBT). The intervention occurred in two distinct periods, separated by one week apart, as this was a crossover study, so volunteers were submitted to placebo or LLLT (830 nm, 8 J/cm2), on the muscles: gastrocnemius, soleus, tibialis previous and long and short fibular. Results the analysis of baropodometry for both dynamic and static found no significant differences for the intervention group and the control group. Similar results were observed for SEBT. Conclusion The application of the LLLT, in the proposed parameters, did not influence the proprioception in young women.(AU)

The morphological and functional effects of exercise in the aquatic environment, performed before and/or after sciatic nerve compression in Wistar rats.

The aim of this study was to evaluate the effects of exercise in the aquatic environment, performed before and/or after sciatic nerve compression in Wistar rats on morphological and functional parameters. Twenty-five Wistar rats were divided into the following groups: control (C), lesion (L), trained+lesion (TL), lesion+exercise (LE), and training+lesion+exercise (TLE), who underwent right sciatic nerve compression on day 21 of the experiment. The TL and TLE groups were submitted to a jumping exercise in a water environment for 20 days prior to injury and the LE and TLE groups after injury. The functional analysis was carried out using the sciatic functional index (SFI). On the last day of the experiment, the right sciatic nerves were collected, processed and analysed according to morphology and morphometry. The C group showed higher SFI in relation to the other groups. In the morphometric analysis, in comparison to C, all groups showed a decrease in the diameter of the injured nerve fibre, the myelin sheath and an increase in the percentage of connective tissue. There was a decrease in axon diameter in L, TL, and LE groups and a decrease in the density of nerve fibres in the TL and LE groups. The exercise did not affect functional recovery. However, the exercise prior to the injury improved morphology of the nervous tissue, and when performed pre- and postinjury, there was also an improvement in nerve regeneration, but this was not the case with exercise performed after the injury demonstrating worse results.

Nociceptive and Neuronal Evaluation of the Sciatic Nerve of Wistar Rats Subjected to Compression Injury and Treated with Resistive Exercise.

Background. To investigate the climb stairs resistance exercise on nociception and axonal regeneration in the sciatic nerve of rats. Methods. 24 Wistar rats were divided: control group (CG-no injury), exercise group (EG-no injury with physical exercise), lesion group (LG-injury, but without exercise), and treated group (LEG-injury and physical exercise). LG and LEG were subjected to sciatic nerve compression with hemostat. From the 3rd day after injury began treatment with exercise, and after 22 days occurs the removal of a nerve fragment for morphological analysis. Results. Regarding allodynia, CG obtained values less than EG (p = 0.012) and larger than LG and LEG (p < 0.001). Histological results showed that CG and EG had normal appearance, as LG and LEG showed up with large amounts of inflammatory infiltration, degeneration and disruption of nerve fibers, and reduction of the myelin sheath; however LEG presented some regenerated fibers. From the morphometric data there were significant differences, for nerve fiber diameter, comparing CG with LG and LEG and comparing axon diameter and the thickness of the myelin of the CG to others. Conclusion. Climb stairs resistance exercise was not effective to speed up the regenerative process of axons.

Evaluation of nociception and edema in experimental sciatic nerve compression model in Wistar rats treated with cryotherapy / Avaliação da nocicepção e edema em modelo experimental de compressão do nervo isquiático em ratos Wistar tratados com crioterapia

ABSTRACT BACKGROUND AND OBJECTIVES: Considering the scarcity of studies addressing cryotherapy to treat peripheral nervous injuries, this study aimed at evaluating nociception and edema in an experimental sciatic nerve compression model with Wistar rats treated with cryotherapy. METHODS: Forty-two rats were randomly distributed in groups: G1 - control, euthanized in the 15th postoperative day; G2, G3 and G4 - submitted to sciatic nerve compression and euthanized in the 3rd, 8th and 15th postoperative day, respectively; G5, G6 and G7 - submitted to sciatic nerve compression and treated with cryotherapy, euthanized in the 3rd, 8th and 15th postoperative day, respectively. Nociception evaluation at injury site and plantar region, and observation of edema were performed before injury, in the 2nd postoperative day and in the day corresponding to euthanasia of each injured group. Mixed ANOVA was used for statistical analysis, considering significant 5%. RESULTS: There has been decreased pain threshold at injury site in injured groups, however there has been increase in the same groups with regard to evaluations in the 8th and 15th postoperative days. Nociception in the plantar region was similar to previous one, however threshold has not increased. With regard to edema, there has been significant difference in evaluations in the 3rd and 2nd postoperative days corresponding to G1, G4 and G7, which had higher values as compared to pre-injury. CONCLUSION: Cryotherapy has not increased nociceptive threshold or decreased the edema.

RESUMO JUSTIFICATIVA E OBJETIVOS: Considerando a carência de estudos a respeito da crioterapia como tratamento de lesão nervosa periférica, este estudo teve como objetivo avaliar a nocicepção e o edema em modelo experimental de compressão do nervo isquiático em ratos Wistar, tratados com crioterapia. MÉTODOS: Foram utilizados 42 ratos separados aleatoriamente nos grupos: G1 - controle, eutanasiado no 15º de pós-operatório; G2, G3 e G4 - submetidos à compressão do nervo isquiático, eutanasiados no 3º, 8º e 15º de pós-operatório, respectivamente; G5, G6 e G7 - submetidos à compressão do nervo isquiático e tratados com crioterapia, eutanasiados no 3º, 8º e 15º de pós-operatório, respectivamente. As avaliações da nocicepção no local da lesão e na região plantar, e a verificação do edema aconteceram nos momentos pré-lesão, 2º dia de pós-operatório e no dia correspondente a eutanásia de cada grupo lesionado. A análise estatística foi pela ANOVA mista, com nível de significância de 5%. RESULTADOS: No local da lesão houve diminuição do limiar doloroso nos grupos lesionados, entretanto, apresentou aumento do mesmo nos grupos relacionados às avaliações do 8º e 15º de pós-operatório. Já a nocicepção realizada na região plantar foi semelhante à anterior, porém o limar não aumentou. Com relação ao edema, houve diferença significativa na avaliação realizada no 3º e no 2º dias de pós-operatório correspondentes ao G1, G4 e G7, que apresentaram valores maiores comparadas com a pré-lesão. CONCLUSÃO: A crioterapia não auxiliou no aumento do limiar nociceptivo e redução de edema.

Efeitos da estimulação elétrica nervosa transcutânea e da corrente de alta voltagem em indivíduos saudáveis / Effects of transcutaneous electrical nerve stimulation and high voltage in healthy subjects

O objetivo deste trabalho foi comparar a estimulação elétrica nervosa transcutânea (TENS) e a corrente de alta voltagem (AV) em indivíduos saudáveis. Para concretizar tal análise, 20 voluntários realizaram as duas modalidades de eletroestimulação de forma cruzada. A nocicepção foi avaliada por meio de estímulos pressóricos e térmicos no membro superior esquerdo, foi aplicada aeletroanalgesia por 20 minutos, sobre a articulação do cotovelo. Os parâmetros da TENS foram: duração de fase de 200 µs e frequência de 100 Hz. Para AV: 50 µse 100 Hz, polo positivo sobre a região do nervo mediano e negativo sobre o ulnar. Os resultados do estudo não mostraram diferenças significativas para limiar de dor e intensidade da dor ao frio. A AV apresentou-se mais agradável e com maior número de acomodações. Desse modo, é possível constatar que os parâmetros utilizados não foram eficazes para alterar a dor em indivíduos saudáveis e a Alta Voltagem teve maior agradabilidade, porém acomodou mais vezes.

Current analysis compares transcutaneous electrical nerve stimulation and high voltage (HV) on healthy subjects. Twenty volunteers experienced the two electro-stimulating modalities. Nociception was evaluated by pressure and thermal stimuli on the upper left limb and electro-analgesia was applied for 20 minutes on the elbow articulation. TENS parameters comprised: phase of 200 µs and frequency of 100 Hz. In the case of HV: 50 µs and 100 Hz, positive pole on the median nerve region and negative pole on the ulnar region. There were no significant paralimiar differences of pain and pain intensity to the cold. HV was more agreeable and with a great number of adaptations. Parameters employed were not efficacious to change pain in healthy subjects; HV had a greater agreeability albeit accommodated several times.

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.

Avaliação nociceptiva da associação entre exercício físico e fibrina rica em plaquetas em ratos Wistar submetidos ao modelo de compressão de nervo mediano / Nociceptive evaluation of the association between physical exercises and platelet-rich fibrin in Wistar rats submitted to median nerve compression

RESUMO JUSTIFICATIVA E OBJETIVOS: Fibrina rica em plaquetas é uma técnica nova e promissora na aceleração do reparo, com possíveis efeitos analgésicos, contudo, ainda há uma lacuna com relação à lesão nervosa periférica, bem como com a associação com exercícios físicos. Assim, o objetivo deste estudo foi avaliar os efeitos da fibrina rica em plaquetas associada a exercício físico sobre a nocicepção e o edema, em modelo experimental de compressão do nervo mediano. MÉTODOS: Foram utilizados 36 ratos, todos submetidos a compressão do nervo mediano e divididos em seis grupos: G1: sem manipulações adicionais; G2: compressão e tratado com fibrina rica em plaquetas; G3: compressão e tratado com natação livre; G4: compressão e exercício de caminhada em esteira; G5: natação livre + fibrina rica em plaquetas; G6: caminhada em esteira + fibrina rica em plaquetas. O modelo de lesão foi realizado com amarria do nervo mediano, com fio catgut 4.0 cromado. Para obtenção da fibrina rica em plaquetas, 1,5mL de sangue foi centrifugado e o coágulo de fibrina foi posicionado diretamente sobre a região da compressão. Os protocolos de exercício foram realizados durante 2 semanas, entre o 3º e 14º dias de pós-operatório. As avaliações nociceptivas e de edema ocorreram, respectivamente, pelo limiar de retirada de pata e pletismometria, nos momentos prévios à lesão, no 3º, 7º e 15º dias de pós-operatório. RESULTADOS: Não houve diferenças entre os grupos, apenas entre as avaliações, denotando que houve aumento da nocicepção e do edema, o qual perdurou ou foi decaindo, respectivamente, com o passar do tempo. CONCLUSÃO: O uso isolado ou associado da fibrina rica em plaquetas com exercícios físicos não produziu alterações na nocicepção e edema.

ABSTRACT BACKGROUND AND OBJECTIVES: Platelet-rich fibrin is a new and promising technique to accelerate repair, with possible analgesic effects; however, there is still a gap with regard to peripheral nerve injury and the association with physical exercises. So, this study aimed at evaluating the effects of platelet-rich fibrin associated to physical exercises on nociception and edema in experimental median nerve compression model. METHODS: Thirty-six rats, all submitted to median nerve compression, were divided in six groups: G1: without additional manipulation; G2: compression and treated with platelet-rich fibrin; G3: compression and treated with free swimming; G4: compression and walking on a treadmill; G5: free swimming + platelet-rich fibrin; G6: walking on a treadmill + platelet-rich fibrin. Injury was induced by tying the median nerve with chrome plated catgut 4.0. Platelet-rich fibrin was obtained by centrifuging 1.5 mL of blood and positioning the fibrin clot directly on the compression region. Exercises were carried out during two weeks, between the 3rd and 14th postoperative days. Nociception and edema were evaluated, respectively, by flinch threshold and plethysmometer, in moments before injury and in the 3rd, 7th and 15th postoperative days. RESULTS: There have been no differences among groups, only among evaluations, showing increased nociception and edema, which has lasted or improved, respectively, over time. CONCLUSION: Platelet-rich fibrin alone or associated to physical exercises has not changed nociception and edema.

Redução da nocicepção articular induzida pela formalina em ratos tratados com laser de baixa potência 670 ou 830 nm / Reduction of joint nociception induced by formalin in rats treated ith low level laser therapy 670 or 830 nm

Modelo do estudo: estudo experimental, de caráter transversal. Objetivo: avaliar os efeitos do laser de baixa potência (LBP), com comprimento de onda de 670nm e 820nm, na nocicepção de ratos Wistar submetidos à hipernocicepção articular no joelho direito. Metodologia: foram utilizados 18 ratos Wistar, separados em 3 grupos: G1 – não tratados; G2 – tratados com LBP 670 nm; G3 – tratados com LBP 830nm. Para a indução da hipernocicepção foi injetado no espaço articular tíbio-femoral 100 µL de formalina 5%. Para avaliar a nocicepção foi utilizado o filamento de von Frey digital, tanto com pressão sobre o joelho, quanto na região plantar; esta avaliação aconteceu: pré-lesão (AV1), após 15 (AV2), 30 (AV3) e 60(AV4) minutos da indução da hipernocicepção. Para o tratamento com LBP foi usada fluência de 8 J/cm, logo após AV2. Resultados: o limiar de retirada, quando a pressão foi realizada no joelho, mostrou que 670 nm produziu elevação do limiar em AV3 e AV4, retornando para valores semelhantes aos de AV1.Para a região plantar, apenas 830 nm mostrou restauração dos valores em AV4, e foi maior em AV3 ao comparar com o grupo controle. Conclusão: ambos os comprimentos de onda produziram elevação do limiar de retirada da pata, em ratos com hipernocicepção em joelho.

Study design: experimental study of cross-cutting nature. Objective: To evaluate the low level laser therapy (LLLT) effects, with a wavelength of 670 and 820nm, in nociception of Wistar rats submitted to hypernociception in his right knee. Methods: 18 Wistar rats, separated into 3 groups: G1 – untreated; G2– treated with LBP 670 nm; G3 – treated with LBP 830 nm. For the hypernociception induction was injected into the tibiofemoral articular space 100 µL of 5% formalin. To evaluate nociception was used digital von Frey filament, both with pressure on the knee, as in the plantar region. The evaluations occurred: pre-injury (EV1), 15 (EV2), 30 (EV3) and 60 (EV4) minutes after hypernociception induction. For the treatment with LBP was used to 8 J/cm2, after EV2. Results: the with drawal threshold, when the pressure was held at the knee, showed that 670 nm produced threshold elevation in EV3 and EV4, returning to values similar to those of EV1. For the plantar region, only 830 nm showed restoration of values inEV4, and was higher in EV3 when comparing with G1. Conclusion: Both wavelengths produced raising the paw with drawal threshold in rats with knee hypernociception.

Características nociceptivas e histomorfométricasde nervos medianos de ratos com obesidade induzidapelo glutamato monossódico / Nociceptive and histomorphometric characteristics of median nerves of ratswith obesity induced by monosodium glutamate

Objetivos: Comparar a nocicepção e, histomorfometricamente, a secção transversa de nervos periféricos de ratos Wistar submetidos ao modelode obesidade induzida pelo glutamato monossódico com animais controle.Métodos: Foram utilizados ratos Wistar, divididos em grupo obeso e grupo controle. Desde o nascimento, durante os primeiros cinco dias devida, os ratos do grupo obeso receberam uma injeção diária subcutânea de glutamato monossódico (4g/kg de peso corporal/dia), enquanto osratos do grupo controle receberam solução salina hiperosmótica (1,25 g/kg de peso corporal/dia). Foi avaliada a nocicepção, pelo limiar deretirada do membro, com uso de analgesímetro digital tipo Von Frey, com o estímulo dado na região palmar da pata anterior direita. A primeiraavaliação foi realizada cerca de 20 dias antes da eutanásia, sendo a segunda avaliação realizada no dia anterior ao da eutanásia. Posteriormente,foi dissecado o nervo mediano, na região do cotovelo e processado com cortes transversais para análise histológica. As variáveis analisadasforam: número de axônios por campo; diâmetros dos axônios, das fibras e da bainha de mielina, e coeficiente G. Os resultados foram analisadospor meio do teste t de Student para amostras independentes e t pareado, com nível de significância de 5%.Resultados: Foram estudados 14 ratos, sendo sete no grupo obeso e sete no grupo controle. A avaliação da nocicepção mostrou que osanimais do grupo obeso apresentavam menor limiar de retirada. Para os dados histomorfométricos, os resultados não mostraram diferençassignificativas entre os dois grupos estudados.Conclusões: Os animais obesos apresentaram menor limiar nociceptivo, porém não houve diferenças morfométricas dos nervos medianosentre animais submetidos ao modelo de obesidade induzida pelo glutamato monossódico e os controles.

Aims: To compare nociception and, histomorphometrically, the transverse section of peripheral nerves (median) of Wistar rats submitted toobesity model induced by monosodium glutamate with control animals.Methods: Fourteen Wistar rats divided into control and obese groups were used. During the five first days since birth the rats from obese groupreceived a daily subcutaneous injection of monosodium glutamate (4 g/kg body weight/day), while the control group received hypertonic saline(1.25 g/kg body weight/day). Nociception was evaluated by the withdrawal threshold of the limb, using digital analgesymeter type Von Frey,with the stimulus given in the palmar region of the right hind paw. The first assessment was carried out about 20 days before euthanasia, andthe second assessment was performed on the day before euthanasia. Subsequently the median nerve was dissected in the elbow region andprocessed with cross sections for histological analysis. The analyzed variables were: number of axons per ; axons, fibers and myelin sheathdiameters, and G coefficient. The results were analyzed using the t test for independent samples and paired t test, with a significance level of 5%.Results: Fourteen rats were assessed, being seven of the obese group and seven of control group. The evaluation of nociception showed thatthe animals of the obese group had lower withdrawal threshold. For histomorphometric data, the results showed no significant differencesbetween the two groups.Conclusions: The obese animals showed lower nociceptive threshold, however, there were no morphometric differences of the median nervesbetween animals subjected to the model of obesity induced by monosodium glutamate and the control group.