Pharmacological Evidence of Eugenia Brasiliensis Leaves in a Reserpine-Induced Fibromyalgia Model: Antinociceptive, Emotional, Anti-Inflammatory, and Neurotrophic Effects.

Fibromyalgia (FM) is a painful chronic condition that significantly impacts the quality of life, posing challenges for clinical management. Given the difficulty of understanding the pathophysiology and finding new therapeutics, this study explored the effects of a medicinal plant, E. brasiliensis, in an FM model induced by reserpine in Swiss mice. Animals were treated with saline 0.9% (vehicle), duloxetine 10 mg/kg (positive control), or hydroalcoholic extract of E. brasiliensis leaves 300 mg/kg (HEEb). Nociceptive parameters, as well as locomotion, motor coordination, strength, anxiety, and depressive-like behaviors, were evaluated for 10 days. After that, the brain and blood were collected for further analysis of cytokines (interleukin 1? and interleukin 6), brain-derived neurotrophic factor (BDNF), and the immunocontents of total and phosphorylated Tropomyosin receptor kinase B (TrkB). The results demonstrated that the acute and prolonged treatment with HEEb was able to reduce both mechanical and thermal nociception. It was also possible to observe an increase in the strength, without changing locomotion and motor coordination parameters. Interestingly, treatment with HEEb reduces anxious and depressive-like behaviors. Finally, we observed a reduction in inflammatory cytokines in the hippocampus of animals treated with HEEb, while an increase in BDNF was observed in the prefrontal cortex (PFC). However, no alterations related to total and phosphorylated TrkB receptor expression were found. Our study demonstrated the antinociceptive and emotional effects of HEEb in mice, possibly acting on neuroinflammatory and neurotrophic mechanisms. These data provide initial evidence about the E. brasiliensis potential for treating chronic pain.

Effectiveness of Cognitive Functional Therapy Versus Core Exercises and Manual Therapy in Patients With Chronic Low Back Pain After Spinal Surgery: Randomized Controlled Trial.

OBJECTIVE: Our aim was to investigate whether cognitive functional therapy (CFT) was more effective than core exercises and manual therapy (CORE-MT) in improving pain and function for patients with chronic low back pain after spinal surgery. METHODS: This study was a randomized controlled superiority trial in a university hospital and a private physical therapist clinic in Santa Catarina, Brazil. Eighty participants who were 18 to 75 years old and had chronic low back pain after spinal surgery received 4 to 12 treatment sessions of CFT or CORE-MT once per week for a maximum period of 12 weeks. Primary outcomes were pain intensity (numeric pain rating scale, scored from 0 to 10) and function (Patient-Specific Functional Scale, scored from 0 to 10) after intervention. RESULTS: We obtained primary outcome data for 75 participants (93.7%). CFT was more effective, with a large effect size, than CORE-MT in reducing pain intensity (mean difference [MD] = 2.42; 95% CI = 1.69-3.14; effect size [d] = 0.85) and improving function (MD = -2.47; 95% CI = -3.08 to -1.87; effect size = 0.95) after intervention (mean = 10.4 weeks [standard deviation = 2.17] after the beginning of treatment). The differences were maintained at 22 weeks for pain intensity (MD = 1.64; 95% CI = 0.98-2.3; effect size = 0.68) and function (MD = -2.01; 95% CI = -2.6 to -1.41; effect size = 0.81). CONCLUSION: CFT was more effective than CORE-MT, with large effect sizes, and may be an option for patients with chronic low back pain after spinal surgery. IMPACT: CFT reduces pain and improves function, with large effect sizes, compared with CORE-MT. The difference between CFT and CORE-MT was sustained at the midterm follow-up. Treatment with CFT may be an option for patients with chronic low back pain after spinal surgery.

Toxicological and pharmacological effects of Eugenia brasiliensis Lam. (Myrtaceae) leaves in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia brasiliensis Lam., popularly known as "grumixama" or "Brazilian cherry", is widely used in folk medicine with astringent, diuretic, energizing, anti-rheumatic, and anti-inflammatory properties. AIM OF THE STUDY: Despite its traditional use, detailed toxicological studies of Eugenia brasiliensis are few. Thus, in the current study, we evaluate the toxicological effects of hydroalcoholic extract of Eugenia brasiliensis (HEEb) and its antinociceptive and anti-inflammatory activity. MATERIALS AND METHODS: We used male, and female Swiss mice. Acute toxicity study was performed following the Organization for Economic Cooperation and Development (OECD) guideline 425, and subacute toxicity was assessed following OECD guideline 407. We observed behavioral responses, in addition to hematological, biochemical, and histological evaluations. The antinociceptive and anti-inflammatory activity of HEEb were assessed using the Carrageenan-induced mechanical allodynia and paw edema model. Mechanical allodynia, levels of inflammatory cytokines, and oxidative damage were evaluated. RESULTS: The treatment with HEEb was not able to generate important toxicological alterations. Moreover, doses of 100 and 300 mg/kg of HEEb were able to reduce mechanical allodynia, paw edema, and inflammatory cytokines (TNF-α, IL-1ß, and IL-6), decrease malondialdehyde and increase superoxide dismutase enzyme activity in the paw. CONCLUSIONS: This study demonstrated that HEEb does not present important toxic effects. Additionally, an important antinociceptive, anti-inflammatory, and antioxidant potential were observed.

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.

Involvement of GABAergic, glutamatergic, opioidergic, and brain-derived neurotrophic factor systems in the trigeminal neuropathic pain process.

Trigeminal neuropathic pain (TNP) is an intense pain condition characterized by hyperalgesia and allodynia; however, its neural mechanisms are not completely understood. Its management is complex, and studies that investigate its biochemical mechanisms are important for improving clinical approaches. This study aimed to evaluate the involvement of GABAergic, glutamatergic, and opioidergic systems and brain-derived neurotrophic factor (BDNF) levels in the TNP process in rats. TNP is induced by chronic constriction injury of the infraorbital nerve (CCI-ION). Nociceptive responses were evaluated using the facial von Frey test before and after the administration of GABAergic and opioidergic agonists and glutamatergic antagonists. The rats were divided into vehicle-treated control (C), sham-surgery (SS), and CCI-ION groups, and then subdivided into the vehicle (V)-treated SS-V and CCI-ION-V groups, SS-MK801 and CCI-ION-MK801, treated with the N-methyl-d-aspartate receptor selective antagonist MK801; SS-PB and CCI-ION-PB, treated with phenobarbital; SS-BZD and CCI-ION-BZD, treated with diazepam; SS-MOR and CCI-ION-MOR, treated with morphine. BDNF levels were evaluated in the cerebral cortex, brainstem, trigeminal ganglion, infraorbital branch of the trigeminal nerve, and serum. CCI-ION induced facial mechanical hyperalgesia. Phenobarbital and morphine reversed the hyperalgesia induced by CCI-ION, and the CCI-BZD group had an increased nociceptive threshold until 60 min. CCI-ION-GLU increased the nociceptive threshold at 60 min. Cerebral cortex and brainstem BDNF levels increased in the CCI-ION and SS groups. Only the CCI group presented high levels of BDNF in the trigeminal ganglion. Our data suggest the involvement of GABAergic, glutamatergic, and opioidergic systems and peripheral BDNF in the TNP process.

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.

Dry needling increases antioxidant activity and grip force in a rat model of muscle pain.

BACKGROUND: Muscle pain syndromes (MPS) are one of the main causes of functional, structural and metabolic problems, being associated with tissue oxidative damage. Although dry needling is widely used in the treatment of MPS, there is little scientific evidence of its efficacy and underlying mechanisms of action. OBJECTIVES: To investigate the effects of different dry needling techniques on thermal and mechanical hyperalgesia, locomotor and functional activity, and oxidative stress markers in a rat model of muscle pain. METHODS: A total of 48 male Wistar rats underwent injection of the gastrocnemius muscle with control neutral saline (pH 7) and remained untreated (Saline group), or acidic saline (pH 4) and remained untreated (ASA group) or received pregabalin (PG group), deep needling (DN group), superficial needling (SN group) or twitch needling (TN group) with n = 8 rats per group. Mechanical (von Frey test) and thermal hyperalgesia (acetone test), muscle edema (assessed with a caliper), strength and muscle function (grip force evaluation), surface thermography and locomotor and exploratory activities (open field test) were evaluated. The animals were then euthanized, and the gastrocnemius muscle was excised for assessment of oxidative analyses of lipid peroxidation with thiobarbituric acid reactive species (TBA-RS) and total glutathione (GSH) levels. RESULTS: All treatments significantly improved muscle strength and function when compared to the AS group (p < 0.05). Pregabalin reduced locomotor and exploratory activities, while the TN intervention increased the antioxidant response (p < 0.05). CONCLUSION: Dry needling improved strength, functionality and locomotor activity in a rat model of muscle pain. Twitch needling induced an antioxidant effect.

Photobiomodulation and Sida tuberculata combination declines the inflammation's markers in knee-induced osteoarthritis.

The aim of this study was to assess potential combination effects of photobiomodulation therapy (PBMT) with Sida tuberculata extracts on the oxidative stress and antioxidant activity, as well as on the inflammatory process. Rats with knee osteoarthritis (OA) were treated with S. tuberculata extracts and PBMT (904 nm, 18 J/cm2). The animals were evaluated for nociception and edema. The blood, knee lavage and structures, spinal cord, and brainstem were collected for biochemical analyses (lipid peroxidation, protein carbonyl content, superoxide dismutase activity, non-protein thiol levels, and measurement of nitrite/nitrate). The knee structures were also used to measure cytokine levels. PBMT lowered the damage due to oxidative stress in the knee and at distant sites from the lesion. PBMT also reduced the levels of nitric oxide and cytokines, which could explain the nociception reduction mechanism. Similarly, S. tuberculata decreased the damage by oxidative stress, levels of nitrite/nitrate, and cytokines. The therapy combination reduced levels of cytokines and nitrite/nitrate. PBMT and S. tuberculata extracts reduced the oxidative stress and inflammation. It is noteworthy that PBMT increased the antioxidant activity in the knee and at sites distant from the lesion, contributing to a more significant decrease in nociception. The combination of therapies did not present significant effects on the analyzed parameters. Therefore, it is suggested that PBM is sufficient to minimize the signs and symptoms of the knee OA in our rat model.

In vivo effects of exposure to Golden trumpet Handroanthus chrysotrichus in mice.

The Golden trumpet Handroanthus chrysotrichus is a tree that presents beneficial health properties against various diseases. Thus, this study aims to verify the toxicity of H. chrysotrichus bark extract, observing the effects of exposure to this extract in mice. For this, mice were separated in groups: saline (sterile solution .9%); H. chrysotrichus crude extract (HCCE) 10; HCCE 50, and HCCE 100 mg. kg-1 (p.o.). We analyzed HCCE effects on acute (single exposure) and subchronic protocol (14 days exposure). After both exposures, acute, and subchronic, we collected samples from blood, brain, liver, and kidney tissues for biochemical evaluation. In addition, after subchronic exposure, we performed behavioral tests. Acute exposure caused an increase of lipid peroxidation in liver tissue. Moreover, we observed a significant carbonyl increase in liver and brain tissues from HCCE 50 mg. kg-1. Kidneys presented carbonyl increase in mice treated with the highest concentration. Besides, creatinine increased in the group of the acute exposure at HCCE 100 mg. kg-1. Total leukocyte count decreased in all concentrations tested. Sub-chronic exposure at HCCE 100 mg. kg-1 caused a decrease in the number of crossing and an increase in its self-grooming frequency in the open field test. In this exposure, the brain and liver had a significant increase in carbonyl levels in all concentrations. We concluded that H. chrysotrichus cause behavioral and biochemical alterations in mice. HCCE primary targets seem to be the liver, kidneys, and white cells.

Mood disorders are associated with the reduction of brain derived neurotrophic factor in the hypocampus in rats submitted to the hipercaloric diet.

Adipose tissue accumulation, resulting from the consumption of hypercaloric foods, can cause a dysfunction of the endocrine system. Such endocrine changes can influence the expression of various neurochemicals including brain-derived neurotrophic factor (BDNF) - associated with cognitive and emotional problems. Here, we investigated the effects of a hypercaloric diet on depression- and anxiety-like behaviors in young rats along with concomitant changes in BDNF expression levels in the hippocampus. Eight week-old Wistar rats (n = 20) were divided in: control diet (CD) group which received industrial food (n = 8) and hypercaloric diet (HD) group which received animal fat and soybean oil (n = 12). After 45 days on the diet, the animals were evaluated: body weight and blood biochemical analisys. Changes in mood disposition were evaluated using forced swim test and the elevated plus-maze, whereas hippocampal BDNF expression levels were quantified by ELISA. After 45 weeks, the CD group showed a significant increase in body weight relative to the HD group. However, the HD rats had a body fat percentage and exhibited increased level of the biochemical markers. Furthermore, the animals in the HD group presented increased immobility time in the forced swimming test, as well as reduced response to plus-maze test suggesting a depression- and anxiety-like emotional state. In addition, the HD group also showed lower BDNF expression levels in the hippocampus. This study demonstrates that a hypercaloric diet induced increase in adipose tissue concentration in young rats was associated with reduced hippocampal BDNF expression and resulted in an increase in depression- and anxiety-like behaviors. Graphical abstract.

Acupuncture reduces peripheral and brainstem cytokines in rats subjected to lipopolysaccharide-induced inflammation.

BACKGROUND: Lipopolysaccharide (LPS) endotoxins are activators of innate immunity inducing infection and inflammatory responses. Anti-inflammatory drugs can have undesirable side effects. Acupuncture may be an alternative for the treatment of inflammatory processes. OBJECTIVE: We investigated the potential anti-inflammatory effect of manual acupuncture (MA) at SP6 upon LPS-induced peritonitis in rats. METHODS: Peritonitis was induced in rats with an intraperitoneal injection of LPS (0.002, 0.02, 0.2 or 2 µg/kg) in four experimental groups (n = 6 each). A fifth group was injected with sterile saline solution (saline group, n = 6). Four hours after the procedure, peritoneal fluid was collected to determine total cell counts for inflammatory cells, differential leukocyte counts and peritoneal capillary permeability. The LPS dose of 0.02 µg/kg was used in the subsequent experiments as it most successfully induced peritoneal inflammation. Subsequently, five experimental groups (n = 12 rats each) were used: (1) saline, (2) control (untreated LPS group), (3) indomethacin (LPS group treated with indomethacin), (4) NA (LPS group treated with MA at a location not corresponding to any traditional acupuncture point), and (5) SP6 (LPS group treated with verum MA at SP6). Ten minutes after MA or 30 min after indomethacin treatment, the rats received an intraperitoneal injection of LPS. After 4 h, total leukocyte and differential cell counts, myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated in the peritoneal fluid. Cytokine levels were additionally evaluated in the brainstem. RESULTS: SP6 MA and indomethacin treatments reduced inflammatory cell infiltration, vascular permeability and MPO activity in the LPS-exposed rats. Pre-treatment with indomethacin and SP6 MA decreased tumor necrosis factor (TNF)-α levels and preserved interleukin (IL)-10 in the peritoneal fluid. Indomethacin also reduced IL-6 in the peritoneal fluid. In the brainstem, indomethacin reduced IL-1ß, IL-6, TNFα and IL-10, whereas SP6 MA reduced only TNFα and IL-6 levels. CONCLUSIONS: This study clearly demonstrates the anti-inflammatory effect of acupuncture, which we believe may involve the activation of anti-inflammatory neural reflexes in the regulation of peritonitis.

A eletroterapia pode aprimorar o efeito de exercícios cinesiofuncionais no tratamento da dor lombar inespecífica crônica? / ¿Puede la electroterapia mejorar el efecto de los ejercicios kinesiofuncionales en el tratamiento del dolor lumbar crónico inespecífico? / Can electrotherapy improve the effect of kinesio-functional exercises in the treatment of chronic non-specific low back pain?

RESUMO O presente estudo teve como objetivo comparar o efeito de um protocolo de exercícios cinesiofuncionais (ECF) isolados ou associados a corrente interferencial (CI) ou corrente aussie (CA), sobre a intensidade da dor, a mobilidade/flexibilidade, a funcionalidade e a qualidade de vida (QV) de indivíduos com dor lombar inespecífica crônica. Trata-se de um ensaio clínico não randomizado, em que foram selecionados 42 sujeitos aleatorizados em três grupos: GI (treinamentos cinesiofuncional; n=14), GII (treinamentos cinesiofuncional + CI; n=14) e GIII (treinamento cinesiofuncional + CA; n=14). Os indivíduos foram submetidos a dez sessões de tratamento ao longo de 5 semanas e foram avaliados pré e pós-intervenção, usando escala visual analógica de dor (EVA); avaliação da QV pelo questionário SF-36; avaliação da mobilidade/flexibilidade lombar pelo teste de Schober modificado e o teste de sentar e alcançar com o banco de Wells; avaliação da incapacidade funcional através do índice Oswestry; e, para os aspectos depressivos, inventário de depressão de Beck (IDB). Na reavaliação, percebeu-se que houve melhora significativa em todos os grupos experimentais na intensidade da dor (p<0,0001) e na mobilidade/flexibilidade. No SF-36, verificamos que apenas os indivíduos tratados com exercícios associados à corrente elétrica apresentaram melhora dos domínios capacidade física, aspectos físicos e dor. A avaliação do IDB não apresentou modificações pré e pós-intervenção. Conclui-se que a associação das técnicas terapêuticas apresentou maior benefício aos indivíduos da amostra, uma vez que produziu melhora sobre as variáveis avaliadas, como dor, mobilidade/flexibilidade e qualidade de vida.

RESUMEN El presente estudio tuvo por objetivo comparar el efecto de un protocolo de ejercicios kinesiofuncionales (ECF) aislados o asociados con corriente interferencial (CI) o corriente aussie (CA) sobre la intensidad del dolor, la movilidad/flexibilidad, la funcionalidad y la calidad de vida (CV) de las personas con dolor lumbar crónico inespecífico. Este es un ensayo clínico no aleatorizado en el que participaron 42 individuos y se los dividieron al azar en tres grupos: GI (entrenamientos kinesiofuncionales; n=14), GII (entrenamientos kinesiofuncionales + CI; n=14) y GIII (entrenamiento kinesiofuncional + CA; n=14). Se sometieron a los participantes a diez sesiones de tratamiento, durante 5 semanas, y estos pasaron por una evaluación antes y después de la intervención por medio de una escala visual de dolor analógica (EVA); evaluación de la CV por el cuestionario SF-36; evaluación de la movilidad/flexibilidad lumbar utilizando la prueba de Schober modificada y la prueba de sentarse y llegar al banco Wells; evaluación de la incapacidad funcional empelando el índice de Oswestry; y, para los aspectos depresivos, el Inventario de Depresión de Beck (BDI). En la reevaluación, la intensidad del dolor (p<0,0001) y la movilidad/flexibilidad tuvieron una mejora significativa en todos los grupos experimentales. En el SF-36, solo los individuos tratados con ejercicios asociados con corriente eléctrica mejoraron la capacidad física, los aspectos físicos y los dominios del dolor. La evaluación del BDI no cambió antes ni después de la intervención. Se concluye que la asociación entre técnicas terapéuticas tuvo un efecto positivo para los individuos de la muestra por la mejora producida en las variables evaluadas, como el dolor, la movilidad/flexibilidad y la calidad de vida.

ABSTRACT This study aimed to compare the effect of a Kinesio-functional exercise protocol (KFE) isolated or associated with Interferential Current (IC) or Aussie Current (AC) on pain intensity, mobility/flexibility, functionality, and quality of life (QoL) of individuals with chronic non-specific low back pain. This is a non-randomized clinical trial, in which 42 individuals were randomly divided into three groups: GI (KFE; n=14), GII (KFE+IC; n=14) and GIII (KFE+AC, n=14). The individuals underwent 10 treatment sessions (five weeks). The individuals were evaluated before and after the intervention, using the Pain visual analog scale (VAS); the assessment of QoL was conducted using the SF-36 questionnaire; the assessment of lumbar mobility/flexibility, by the modified Schober test and the Wells Bank; the assessment of functional disability, using the Oswestry Index; and for depressive aspects, the Beck Depression Inventory (BDI) was used. In the reassessment, we observed a significant improvement in all experimental groups regarding pain intensity (p <0.0001) and mobility/flexibility. In SF-36, we found that only individuals treated with exercises associated with electrical current improved their physical capacity, physical aspects, and pain domains. The BDI assessment did not show any changes before or after the intervention. We conclude that the association of therapeutic techniques showed greater benefit to the individuals in the sample since it improved the evaluated variables, such as pain, mobility/flexibility, and quality of life.

Transcutaneous electrical nerve stimulation, acupuncture, and spinal cord stimulation on neuropathic, inflammatory and, non-inflammatory pain in rat models.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS), manual acupuncture (MA), and spinal cord stimulation (SCS) are used to treat a variety of pain conditions. These non-pharmacological treatments are often thought to work through similar mechanisms, and thus should have similar effects for different types of pain. However, it is unclear if each of these treatments work equally well on each type of pain condition. The purpose of this study was to compared the effects of TENS, MA, and SCS on neuropathic, inflammatory, and non-inflammatory pain models. METHODS: TENS 60 Hz, 200 µs, 90% motor threshold (MT), SCS was applied at 60 Hz, an intensity of 90% MT, and a 0.25 ms pulse width. MA was performed by inserting a stainless-steel needle to a depth of about 4-5 mm at the Sanyinjiao (SP6) and Zusanli (ST36) acupoints on a spared nerve injury (SNI), knee joint inflammation (3% carrageenan), and non-inflammatory muscle pain (intramuscular pH 4.0 injections) in rats. Mechanical withdrawal thresholds of the paw, muscle, and/or joint were assessed before and after induction of the pain model, and daily before and after treatment. RESULTS: The reduced withdrawal thresholds were significantly reversed by application of either TENS or SCS (P < 0.05). MA, on the other hand, increased the withdrawal threshold in animals with SNI and joint inflammation, but not chronic muscle pain. CONCLUSIONS: TENS and SCS produce similar effects in neuropathic, inflammatory and non-inflammatory muscle pain models while MA is only effective in inflammatory and neuropathic pain models.

Sida tuberculata reduces oxidative stress and pain caused by the knee osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Knee osteoarthritis (OA) cause pain and edema, as well as unbalance between the production of reactive oxygen species and antioxidant activity. These problems interfere with the articular function, leading to a significant loss of life quality. Sida tuberculata R.E.Fr. is an herbaceous plant belonging to the Malvaceae family found in southern Brazil. This plant has traditionally been consumed as an aqueous extract and popularly used in the treatment of many diseases, with antioxidant and antimicrobial activity, reducing pain and inflammation. AIM OF THE STUDY: To verify the effects of S. tuberculata extract obtained from leaves on oxidative, toxic and nociceptive parameters induced by knee OA in rats. MATERIALS AND METHODS: Aqueous extracts of S. tuberculata were evaluated under phytochemical analyses. Knee Osteoarthritis was induced in rats with monosodium iodoacetate (1.5 mg/50 µl) and treated with S. tuberculata extract. The animals were treated orally with 3 doses of S. tuberculata extract (STE): 1.5, 5 and 15 mg/ml, for 14 days. For biochemical analyses, the following tests were performed: lipid peroxidation, carbonylated protein content, superoxide dismutase activity, non-protein thiol levels and myeloperoxidase activity. For the evaluation of pain and edema we verify mechanical and thermal hyperalgesia, spontaneous pain observation and measurement of knee edema with a caliper. For histological evaluations, the animal knee joints were removed. For toxicity evaluation, the levels of aspartate aminotransferase, alanine aminotransferase and urea, as well as the relative weight of the organs were analyzed. RESULTS: The S. tuberculata phytochemical analyses showed the majority peak corresponding to 20-hydroxyecdysone (20HE). The plant extract decreased damages related to oxidative stress in the blood serum (lipid peroxidation and carbonyl content) Overall, the STE 5 mg Group presented the greater statistical significance, in the blood serum samples, in relation to the other groups, being the most relevant result. The S. tuberculata groups presented pain decrease, lower neutrophil activity in the knee, and increased blood serum activity. The animals of S. tuberculata groups showed a decrease in mechanical hyperalgesia. The animals treated also presented lower scores for spontaneous pain. It was observed that the dose of 5 mg presented, once again, more expressive results, since the animals of this group had a higher frequency (greater number of days) with significant decrease of pain. In the histological analysis, in the STE 5 mg group, the articular cartilage lesions were observed at an intermediate point between the damage found in the MIA and Diclofenac groups. Besides that, the STE did not show significant changes in oxidative stress damage in liver and kidney samples. Blood serum samples did not indicate significant differences in liver and renal function. As well as, there were no differences in mean relative body weights in relation to control groups (Salina and MIA). CONCLUSION: S. tuberculata reduced the damage due to oxidative stress and pain caused by knee osteoarthritis in rats. In addition, the extract presented no toxicity. Our results suggest that S. tuberculata seems to have a therapeutic potential in the osteoarthritis treatment.

Sida tuberculata extract reduces the nociceptive response by chemical noxious stimuli in mice: Implications for mechanism of action, relation to chemical composition and molecular docking.

Sida tuberculata R.E.Fr. (Malvaceae) is a medicinal plant widely found in Southern Brazil, and popularly used for inflammatory disorders and to pain relief. A phytochemical analysis followed by an investigation about antinociceptive potential and mechanism of action were performed with leaves and roots extracts. Methanolic extracts, designated as S. tuberculata leaves extract (STLE) and S. tuberculata roots extract, were analyzed both by UHPLC­MS. The in vivo antinociceptive potential of STLE (10­300 mg kg−1) was assessed in mice subjected to the acetic acid­induced abdominal writhes and formalin model. Agonist/antagonist tests and computational docking suggest the involvement of opioid and adenosinergic systems. The main chemical class detected on extracts was the ecdysteroids, and 20­hydoxyecdysone (20HE) was confirmed as the major phytoconstituent. The pretreatment with STLE (100 mg kg−1) reduced more than 70% abdominal contortions induced by acetic acid model and produced significant inhibition on formalin­induced licking response. The mechanism of action study revealed STLE might act through opioid and adenosine systems. Molecular docking suggested kaempferol derivative and 20HE might interacting with µ­opioid receptor. Thus, the results suggest the existence of antinociceptive potential from S. tuberculata extracts being in accordance to the traditional use.

Evaluation of monosodium iodoacetate dosage to induce knee osteoarthritis: Relation with oxidative stress and pain.

AIM: To determine the dose of monosodium iodoacetate (MIA) required to induce oxidative stress, as well as pain and edema; to confirm the induction of knee osteoarthritis (OA) symptoms in rats by the presence of reactive oxygen species (ROS) and reduction of antioxidant agents; and to verify the presence of histopathological injury in these affected joints. METHOD: Biological markers of oxidative stress, pain, knee edema, and cartilage degeneration provided by different doses of MIA (0.5; 1.0 or 1.5 mg) in rat knee joints were analyzed. The animal evaluations were conducted during 15 days for mechanical and cold hypersensitivity, spontaneous pain and edema. After that, blood serum, intra-articular lavage and structures of knee, spinal cord and brainstem were collected for biochemical analysis; moreover, the knees were removed for histological evaluation. RESULTS: This study demonstrates that the highest dose of MIA (1.5 mg) increased the oxidative stress markers and reduced the antioxidant reactions, both in the focus of the lesion and in distant sites. MIA also induced the inflammatory process, characterized by pain, edema, increase in neutrophil count and articular damage. CONCLUSION: This model provides a basis for the exploration of underlying mechanisms in OA and the identification of mechanisms that may guide therapy and the discovery of OA signals and symptoms.

Corrente Russa associada ao ultrassom ou a fonoforese reduz o fibro edema gelóide / Russian Current associated with ultrasound or phonophoresis reduces cellulite

Introdução: O fibro edema gelóide (FEG) ocasiona deformações locais no tecido subcutâneo. Correntes excito motoras, como a corrente russa (CR), e métodos que associam efeitos mecânicos e térmicos no tecido, como o ultrassom (US), são usados para tratar a FEG. O US pode ainda ser aplicado com a fonoforese (FN) para aumentar a absorção percutânea de princípios ativos. Objetivo: Verificar o efeito da CR associada ao US ou à FN no tratamento da FEG em glúteos e coxas de mulheres jovens. Métodos: Participaram mulheres com FEG que realizaram 10 sessões de CR com US ou com FN. As voluntárias foram avaliadas antes e após os tratamentos. Resultados: Obteve-se diminuição da espessura das dobras cutâneas, redução do grau de FEG, redução da distorção da imagem corporal e índice de satisfação elevado das voluntárias com os resultados de ambos tratamentos, porém a FN associada à CR apresentou efeito mais evidente. Conclusão: Os tratamentos utilizados fornecem resultados rápidos e satisfatórios na redução do FEG.

Introduction: Geloid fibroedema (GF) or Cellulitis causes local deformations in the subcutaneous tissue. Electric Stimulation Therapy, such as the Russian Current (RC), and methods associating mechanical and thermal effects on tissue, such as Ultrasound (US), are used to treat GF. US can still be applied with Phonophoresis (Ph) to increase percutaneous absorption of active principles. Objective: To verify the effect of RC associated with US or Ph in the treatment of GF in glutes and thighs of young women. Methods: GF women who performed 10 sessions of RC with US or with Ph participated. The volunteers were evaluated before and after the treatments. Results: There was a reduction in the thickness of the skin folds, reduction of the GF degree, reduction of the body image distortion and high index of satisfaction of the volunteers with the results of both treatments, but the Ph associated to the CR showed a more evident effect. Conclusion: The treatments used provide fast and satisfactory results in the reduction of GF.

Efeito dos exercícios de fortalecimento, de marcha e de equilíbrio no tratamento de osteoartrite de joelho / Eff ect of strength, gait and balance exercises, in the treatment of knee osteoarthritis

A osteoartrite (OA) é uma doença reumática, degenerativa e progressiva que atinge as articulações sinoviais. Indivíduos com OA apresentam dor, rigidez articular matinal, sinais infl amatórios, crepitações, hipotrofi a muscular e limitações na amplitude de movimento. A fi sioterapia utiliza de recursos terapêuticos, como exercícios, para reduzir os sintomas e melhorar a qualidade de vida do indivíduo com OA. Este trabalho teve por fi nalidade verifi car o efeito da associação de exercícios de fortalecimento, de marcha e de equilíbrio sobre a dor, a amplitude de movimento, o equilíbrio, a qualidade de vida e a capacidade funcional de indivíduos com OA de joelho. Estudo clínico cego, no qual participaram 16 indivíduos com OA de joelho de ambos os gêneros e idade média de 61,38 ±16,10 anos. Os participantes realizaram 12 sessões de fi sioterapia, realizando exercícios de fortalecimento, marcha e equilíbrio. Eles foram avaliados antes e após o tratamento, por meio da escala visual analógica de dor, do questionário Western Ontario and McMaster Universities Osteoarthritis (WOMAC), do questionário de qualidade de vida SF-36, da goniometria, teste Timed Up and Go, teste de caminhada rápida de 10 metros, Escala de equilíbrio de Berg e teste de Romberg. Obteve-se diminuição da dor e, melhora da qualidade de vida nos domínios do questionário SF-36: aspectos funcionais, dor, estado geral de saúde e aspectos emocionais. O tratamento também proporcionou aumento da amplitude de movimento em fl exão, melhorou o equilíbrio no teste de Romberg com os olhos fechados e funcionalidade nos domínios rigidez e aspecto funcional do questionário WOMAC. Os exercícios de fortalecimento, marcha e equilíbrio foram capazes de reduzir a dor, melhorar a amplitude de movimento, equilíbrio, funcionalidade e qualidade de vida de pacientes com OA de joelho....(AU)

Osteoarthritis (OA) is a rheumatic, degenerative and progressive disease that aff ects the synovial joints. Individuals with OA experience pain, morning stiff ness, infl ammatory signals, crackles, muscular atrophy and limitations in range of motion. Physical therapy uses therapeutic resources, such as exercise, to reduce symptoms and improve the quality of life of individuals with OA. This study aimed to verify the eff ect of strengthening exercises association, gait and balance on pain, range of motion, balance, quality of life and functional capacity of patients with knee OA. Blind clinical study, which involved 16 subjects with knee OA of both genders, mean age of 61.38 ± 16.10 years. The participants underwent 12 physiotherapy sessions, performing strengthening exercises, gait and balance. They were evaluated before and after treatment by visual analogue pain scale, the questionnaire Western Ontario and McMaster Universities Osteoarthritis (WOMAC), the quality of life questionnaire SF-36, goniometry, Timed Up and Go test, test fast walk 10 meters, Berg balance Scale and Romberg test. Obtained decreased pain and improved quality of life in the domains of the SF-36 questionnaire: functional aspects, pain, general health and emotional aspects. The treatment also provided increased range of motion in fl exion, improved balance in the Romberg test with eyes closed and functionality in the areas stiff ness and functional aspect of the WOMAC questionnaire. Strengthening exercises, gait and balance were able to reduce pain, improve range of motion, balance, functionality and quality of life of patients with knee OA....(AU)

Terapia combinada associada à drenagem linfática reduz lipodistrofia localizada no abdômen de mulheres jovens / Combined therapy associated with lymphatic drainage reduce lipodystrophy located on abdomen of young women

Introdução: A Lipodistrofia localizada (LL) é o excesso de tecido adiposo em locais do corpo. A terapia combinada (TC) e a drenagem linfática manual (DLM) podem agir na redução da LL. Objetivo: Verificar o efeito da TC associada à DLM sobre a LL no abdômen de mulheres jovens e o grau de satisfação da imagem corporal. Método: Estudo clínico cego, no qual participaram 12 mulheres com LL no abdômen. As participantes realizaram 10 sessões de TC associado a DLM. As mulheres foram avaliadas antes e após o tratamento, através da aferição do peso e altura; perimetria abdominal; adipometria; registro fotográfico; e aplicação da Escala de Satisfação com a Imagem Corporal. Resultados: Redução da perimetria, da dobra cutânea na região, da porcentagem de gordura corporal e melhora da satisfação da imagem corporal dos indivíduos. Conclusão: O tratamento apresentou resultados rápidos e satisfatórios na redução da LL no abdômen de mulheres. (AU)

Introduction: Localized Lipodystrophy (LL) is the excess of adipose tissue at body sites. Combination therapy (CT) and manual lymphatic drainage (DLM) may act to reduce LL. Objective: To verify the effect of CT associated with DLM on the LL in the abdomen of young women and the degree of body image satisfaction. Method: Blind clinical study, in which 12 women with LL participated in the abdomen. Participants underwent 10 CT sessions associated with DLM. The women were evaluated before and after treatment by measuring the weight and height; abdominal circumference; plicometry; photographic record; and application of Satisfaction Scale with Body Image. Results: We observed reduction in abdominal circumference, skinfold thickness, reducing the percentage of body fat and improved body image satisfaction of individuals. Conclusion: The treatment presented fast and satisfactory results in the reduction of LL in the abdomen of women. (AU)

Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord.

AIM: To investigate the antinociceptive, antiedematogenic and chondroprotective effects of diacerein (DIA) in a model of joint inflammation induced by complete Freund's adjuvant (CFA), as well as to investigate the involvement of metalloproteinase (MMP)-9, transient receptor potential vanilloid 1 (TRPV1) and glial cells in DIA's action mechanism. METHODS: Complete Freund's adjuvant was injected into the knee joint of male rats. We observed mechanical and cold hypersensitivity, vocalization and spontaneous pain-related behaviors, as well as edema of the knee. Tissue samples of the knee were stained with Cason`s technique and the thickness of the condilus cartilage was measured. Immunohistochemical analysis was performed on the spinal cord using anti-GFAP (glial fibrillary acidic protein), anti-MMP and anti-TRPV1 antibodies. Sections of the dorsal horns of the spinal cord were captured and an optical density was obtained. RESULTS: Complete Freund's adjuvant induced mechanical and thermal hypersensitivity, as well as joint edema and changes in the synovial membrane and cartilage. DIA (30 mg/kg, orally, daily) significantly inhibited mechanical (58 ± 10-87 ± 3%) and thermal (66 ± 12-87 ± 8%) hypersensitivity, vocalization (83 ± 5-41 ± 11%), spontaneous pain score, joint swelling (60 ± 6-40 ± 9%), as well as the histological changes induced by CFA. In addition, DIA inhibited astrocyte activation, and prevented the increase of MMP-9 and TRPV1 expression in the spinal cord of the animals subjected to CFA injections. CONCLUSIONS: In short, this study shows that DIA reduces joint damage and hypersensitivity associated with inflammation induced by CFA through the inhibition of astroglial activation and decreases the expression of TRPV1 and MMP-9 in the rat spinal cord.