Animal models of complex regional pain syndrome: A scoping review.

BACKGROUND: complex regional pain syndrome (CRPS) leads to a debilitating chronic pain condition. The lack of cause, etiology, and treatment for CRPS has been widely explored in animal models. OBJECTIVE: Provide a comprehensive framework of the animal models used for investigating CRPS. ELIGIBILITY CRITERIA: Preclinical studies to induce the characteristics of CRPS, with a control group, in any language or publication date. SOURCES OF EVIDENCE: The search was performed in the Medline (PubMed) and ScienceDirect databases. RESULTS: 93 studies are included. The main objective of the included studies was to understand the CRPS model. Rats, males and adults, exposed to ischemia/reperfusion of the paw or fracture of the tibia were the most common characteristics. Nociceptive evaluation using von Frey monofilaments was the most widely adopted in the studies. CONCLUSIONS: For the best translational science between the animal models and individuals with CRPS, future studies should include more heterogeneous animals, and multiple assessment tools, in addition to improving the description and performance of measures that reduce the risk of bias.

The effect of modafinil on passive avoidance memory, brain level of BDNF and oxidative stress markers in sepsis survivor rats.

Propose/aim of study: Modafinil (MD) is a psychostimulant drug used off-label and cognitive dysfunction may be a significant emerging treatment target for this drug. The objective of this study was to evaluate the effect of MD on the neurochemical parameters and memory impairment of rats submitted to sepsis by cecal ligation and perforation (CLP).Material and method: Male Wistar rats (250-350g) were submitted to CLP, or sham as control, and divided into the sham + water, sham + MD (300 mg/kg), CLP + water, and CLP + MD (300 mg/kg) groups. Ten days after the administration of MD and CLP, the rats were submitted to a memory test by passive avoidance apparatus being sacrificed. The nitrite and nitrate (N/N) concentration, myeloperoxidase (MPO) and catalase (CAT) activity, lipid and protein oxidative damage, and brain-derived neurotrophic factor (BDNF) levels were measured in the prefrontal cortex and hippocampus.Results: The passive avoidance test verified an increase in the latency time compared training and test section in the groups sham + water and CLP + MD. Decreased N/N concentration and MPO activity were verified in the prefrontal cortex of rats submitted to CLP and MD treatment, as well as reduced protein and lipid oxidative damage in the hippocampus, which was accompanied by increased CAT activity and BDNF levels.Conclusion: Our data indicate the role of MD in attenuating oxidative stress parameters, the alteration of BDNF, and an improvement in memory impairment in rats ten days after induction of sepsis.

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.

Karate Training Improves Metabolic Health in Overweight and Obese Adolescents: A Randomized Clinical Trial.

PURPOSE: This study evaluated the effects of 12 weeks of karate training on cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. METHOD: Seventy adolescents were randomized into 2 groups: control received nutritional and psychological interventions once a week for 12 weeks, and treatment received nutritional and psychological interventions once a week, plus 3 karate sessions per week, for 12 weeks. The main outcome measure was improvement in cardiometabolic parameters, oxidative stress, and inflammation. RESULTS: After the intervention period, the treatment group showed a reduction in resting heart rate (77.86 [10.89]), high-density lipoprotein cholesterol (40.86 [8.31]), and triglycerides (75.18 [32.29]) and an increase in low-density lipoprotein cholesterol (95.64 [42.53]) in relation to pretraining. Regarding oxidative stress markers, there was a reduction in protein carbonylation (0.07 [0.06]) and nitric oxide (1.39 [1.11]) and an increase in superoxide dismutase (0.68 [0.31]) and glutathione (0.11 [0.08]) compared with pretraining. With respect to inflammation, adiponectin increased (14.54 [5.36]) after the intervention when compared with preintervention. CONCLUSION: The study concluded that the intervention may improve cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Long-term effects need to be evaluated.

Decrease of IL-1ß and TNF in the Spinal Cord Mediates Analgesia Produced by Ankle Joint Mobilization in Complete Freund Adjuvant-Induced Inflammation Mice Model.

OBJECTIVE: This study aims to investigate the effects of ankle joint mobilization (AJM) on mechanical hyperalgesia and peripheral and central inflammatory biomarkers after intraplantar (i.pl.) Complete Freund's Adjuvant (CFA)-induced inflammation. METHODS: Male Swiss mice were randomly assigned to 3 groups (n = 7): Saline/Sham, CFA/Sham, and CFA/AJM. Five AJM sessions were carried out at 6, 24, 48, 72, and 96 h after CFA injection. von Frey test was used to assess mechanical hyperalgesia. Tissues from paw skin, paw muscle and spinal cord were collected to measure pro-inflammatory (TNF, IL-1ß) and anti-inflammatory cytokines (IL-4, IL-10, and TGF-ß1) by ELISA. The macrophage phenotype at the inflammation site was evaluated by Western blotting assay using the Nitric Oxide Synthase 2 (NOS 2) and Arginase-1 immunocontent to identify M1 and M2 macrophages, respectively. RESULTS: Our results confirm a consistent analgesic effect of AJM following the second treatment session. AJM did not change cytokines levels at the inflammatory site, although it promoted a reduction in M2 macrophages. Also, there was a reduction in the levels of pro-inflammatory cytokines IL-1ß and TNF in the spinal cord. CONCLUSION: Taken together, the results confirm the anti-hyperalgesic effect of AJM and suggest a central neuroimmunomodulatory effect in a model of persistent inflammation targeting the pro-inflammatory cytokines IL-1ß and TNF.

Lipoic Acid and Fish Oil Combination Potentiates Neuroinflammation and Oxidative Stress Regulation and Prevents Cognitive Decline of Rats After Sepsis.

Sepsis causes organ dysfunction due to an infection, and it may impact the central nervous system. Neuroinflammation and oxidative stress are related to brain dysfunction after sepsis. Both processes affect microglia activation, neurotrophin production, and long-term cognition. Fish oil (FO) is an anti-inflammatory compound, and lipoic acid (LA) is a universal antioxidant substance. They exert neuroprotective roles when administered alone. We aimed at determining the effect of FO+LA combination on microglia activation and brain dysfunction after sepsis. Microglia cells from neonatal pups were co-treated with lipopolysaccharide (LPS) and FO or LA, alone or combined, for 24 h. Cytokine levels were measured. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) and treated orally with FO, LA, or FO+LA. At 24 h after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of cytokines, myeloperoxidase (MPO) activity, protein carbonyls, superoxide dismutase (SOD), and catalase (CAT) activity. At 10 days after surgery, brain-derived neurotrophic factor (BDNF) levels were determined and behavioral tests were performed. The combination diminished in vitro levels of pro-inflammatory cytokines. The combination reduced TNF-α in the cortex, IL-1ß in the prefrontal cortex, as well as MPO activity, and decreased protein carbonyls formation in all structures. The combination enhanced catalase activity in the prefrontal cortex and hippocampus, elevated BDNF levels in all structures, and prevented behavioral impairment. In summary, the combination was effective in preventing cognitive damage by reducing neuroinflammation and oxidative stress and increasing BDNF levels.

Effects of physical exercise on lung inflammation in animal models of chronic allergic lung inflammation: a systematic review.

We performed a systematic review to identify and summarize the effects of distinctive aerobic exercise (AE) protocols on chronic allergic lung inflammation reported in asthma animal models. We identified 255 preclinical studies of asthma and AE protocols by comprehensive searches in PubMed, ScienceDirect and LILACS for peer-reviewed journals, using the search components "exercise," "lung inflammation," and "asthma," without restrictions on publication date. Twenty-two studies were selected that met all eligibility criteria. Most studies used an ovalbumin experimental model and performed experiments with BALB/c mice. Most studies performed treadmill AE, using protocols of 30 to 60 minutes, 3 to 5 times/week, for 4 to 8 weeks. The results showed that the effects of AE on lungs were protocol dependent, but generaly, there was a decrease in inflammatory cell influx and Th2 cytokines, as well as an increase in anti-inflammatory defenses. However, the immunoregulation of globulins and nitric oxide levels in asthma seemed to be associated with the onset of AE. The results suggest that AE plays an important immunoregulatory role in animal models of asthma, with effects mainly mediated by increased anti-inflammatory defenses and reduced Th2 response. In parallel, prophylactic and therapeutic AE also played important roles in decreasing bronchial responsiveness and attenuating lung remodeling in animal models of asthma, secondary outcomes in this systematic review. The review protocol was published for free access in October 2017 on the Systematic Review Facility (SyRF) platform (http://syrf.org.uk/protocols/).

Sickness Behavior Score Is Associated with Neuroinflammation and Late Behavioral Changes in Polymicrobial Sepsis Animal Model.

The use of reliable scores is a constant development in critical illness. According to Sepsis-3 consensus, the use of Sequential Organ Failure Assessment (SOFA) score of 2 or more is associated with a higher mortality of sepsis patients. In experimental research, due murine animal model limitations, the use of a score systems can be an alternative to assess sepsis severity. In this work, we suggest a sickness behavior score (SBS) that uses physiological variables to assess sepsis severity and mortality. Animals were evaluated daily by the presence of six indicators of sickness behavior: temperature alteration, preference of water/sucrose, liquid intake, food intake, body weight, and movimentation. Male adult Wistar rats were evaluated daily after sepsis induction by cecal ligation and puncture (CLP) or laparotomy only (sham) for determination of SBS. Oxidative stress, IL-6, and HPA axis markers (corticosterone and adrenal gland weight) were evaluated 24 h after CLP to determine the correlation with the acute SBS and neuroinflammation. Also, BDNF and four cognitive behavioral tests were correlated with the chronic SBS, i.e., sum of 8 days after surgery. In result, septic rats presented higher SBS than sham animals. Sepsis severity markers were associated with acute and chronic SBS. Also, SBS was negative correlated with the cognitive tests. In conclusion, SBS shows to be reliable score to predict sepsis severity and mortality. The use of score system provides the analysis of global sickness behavior, beyond evaluation of each parameter individually.

Fish oil-rich lipid emulsion modulates neuroinflammation and prevents long-term cognitive dysfunction after sepsis.

OBJECTIVES: Sepsis is a severe organic dysfunction caused by an infection that affects the normal regulation of several organ systems, including the central nervous system. Inflammation and oxidative stress play crucial roles in the development of brain dysfunction in sepsis. The aim of this study was to determine the effect of a fish oil (FO)-55-enriched lipid emulsion as an important anti-inflammatory compound on brain dysfunction in septic rats. METHODS: Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with FO (600 µL/kg after CLP) or vehicle (saline; sal). Animals were divided into sham+sal, sham+FO, CLP+sal and CLP+FO groups. At 24 h and 10 d after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of interleukin (IL)-1ß and IL-10, blood-brain barrier permeability, nitrite/nitrate concentration, myeloperoxidase activity, thiobarbituric acid reactive species formation, protein carbonyls, superoxide dismutase and catalase activity, and brain-derived neurotrophic factor levels. Behavioral tasks were performed 10 d after surgery. RESULTS: FO reduced BBB permeability in the prefrontal cortex and total cortex of septic rats, decreased IL-1ß levels and protein carbonylation in all brain structures, and diminished myeloperoxidase activity in the hippocampus and prefrontal cortex. FO enhanced brain-derived neurotrophic factor levels in the hippocampus and prefrontal cortex and prevented cognitive impairment. CONCLUSIONS: FO diminishes the negative effect of polymicrobial sepsis in the rat brain by reducing inflammatory and oxidative stress markers.

Neuropathic pain after spinal cord injury and physical exercise in animal models: A systematic review and meta-analysis.

The aim of this systematic review was to summarize the effects of physical exercise on neuropathic pain (NP) in animal models of SCI. The search was conducted in Medline and Science Direct to identify experimental preclinical studies involving animal models of SCI, physical exercise as an intervention and the assessment of NP. Fifteen articles met the eligibility criteria. The review shows that in studies of NP involving animal models of SCI, rodents are the most common species. Thoracic contusion is the most common injury and mechanical and thermal nociception are the most frequently assessed NP components. The benefits of physical exercise vary according to its starting period and total duration. In addition, there is considerable heterogeneity regarding the type and intensity of exercise capable of alleviating NP after SCI. Furthermore, physical exercise has beneficial effects on mechanical, thermal and cold nociception, and spontaneous pain. These results are weakened by the paucity of studies involving these pain outcomes. The review protocol is published for free access on the SyRF platform (http://syrf.org.uk/protocols/).

Photobiomodulation therapy in knee osteoarthritis reduces oxidative stress and inflammatory cytokines in rats.

Knee osteoarthritis (OA) is a chronic disease that causes pain and gradual degeneration of the articular cartilage. In this study, MIA-induced OA knee model was used in rats to test the effects of the photobiomodulation therapy (PBM). We analyzed the inflammatory process (pain and cytokine levels), and its influence on the oxidative stress and antioxidant capacity. Knee OA was induced by monosodium iodoacetate (MIA) intra-articular injection (1.5 mg/50 µL) and the rats were treated with eight sessions of PBM 3 days/week (904 nm, 6 or 18 J/cm2 ). For each animal, mechanical and cold hyperalgesia and spontaneous pain were evaluated; biological analyses were performed in blood serum, intra-articular lavage, knee structures, spinal cord and brainstem. Cytokine assays were performed in knee, spinal cord and brainstem samples. The effects of the 18 J/cm2 dose of PBM were promising in reducing pain and neutrophil activity in knee samples, together with reducing oxidative stress damage in blood serum and spinal cord samples. PBM improved the antioxidant capacity in blood serum and brainstem, and decreased the knee pro-inflammatory cytokine levels. Our study demonstrated that PBM decreased oxidative damage, inflammation and pain. Therefore, this therapy could be an important tool in the treatment of knee OA.

Clinical Instruments for Measuring Unsupported Sitting Balance in Subjects with Spinal Cord Injury: A Systematic Review.

Background: Evidence of intervention effectiveness depends on, among other things, the use of a common set of valid and reliable measures that are responsive to change and reflect clinically important outcomes. Objective: To identify clinical assessment instruments with properties for measuring unsupported sitting balance in subjects with spinal cord injury (SCI). Methods: Bibliographic databases (PubMed, Science Direct, CINAHL, and Central) were searched for articles with the key words "spinal cord injury," "unsupported sitting," and "outcome assessment" in combination with a specific methodological search filter for each database. Studies describing the application of any assessment instrument for measuring unsupported sitting balance in subjects with SCI, which had the evaluation of any measurement property, were included in the review. Publication details, measure's name, setting, summary statistics, measurement properties (reliability, validity, responsiveness), and statistical significance (p values) were extracted. Results: Eight hundred forty publications were identified; 8 articles were included in the systematic review. Twelve instruments were identified and analyzed, showing limited and incomplete measurement properties. Among them, 10 addressed activity, 1 addressed structures/body functions, and 1 addressed both activity and structures/body functions domains of the International Classification of Functioning, Disability and Health (ICF). Conclusion: Based mainly on the measurement properties and the development of the instruments analyzed in this review, the Sitting Balance Measure, the Trunk Control Test, and the Set of Assessment Tools for Measuring Unsupported Sitting seem to be the most appropriate and recommended measures to assess unsupported sitting in subjects with SCI.

Isokinetic performance of ankle evertor and invertor muscles in adolescent female volleyball athletes

This study aimed to analyze the muscular performance of evertor and invertor ankle muscles of adolescent volleyball athletes. Methods: The information provided by database concerning the isokinetic evaluation of ankle muscles from 20 female volleyball players between the ages of 14-17 years old were analyzed. The isokinetic dynamometer was used in a concentric-concentric mode for the ankle evertor and invertor muscles at angular velocities of 60°/s, and 180°/s. Results: Seven athletes had suffered ankle sprains (6 affected the non-dominant limb and all were lateral ankle sprain) in the one year prior to the isokinetic evaluation. The isokinetic results demonstrated that the mean peak torque values for eversion of the non-dominant limb were significantly lower in comparison to the dominant limb at 60°/s. Moreover, although no difference was observed in the average values of the evertor/invertor ratio between the limbs, the ratios were below the values suggested by the literature. Conclusion: We believe that although the athletes reported no ankle injury and no pain in the previous assessment month, the isokinetic results of the non-dominant limb seemed to be directly related to previous ankle sprains injuries in inversion of this limb. The athletes had similar results to those of subjects clinically diagnosed with ankle joint instabilities despite their being active in sports at the moment of the assessment.(AU)

Análise da marcha em pacientes portadores de doença pulmonar obstrutiva crônica antes e após programa de reabilitação pulmonar / Chronic obstructive pulmonary disease patients gait analysis before and after a pulmonary rehabilitation program

Introdução: A Doença Pulmonar Obstrutiva Crônica (DPOC) é uma patologia respiratória que está relacionada à diminuição funcional, e pode provocar alterações da marcha em indivíduos com DPOC. Objetivo: Analisar, através de informações de um banco de dados, os parâmetros da cinemática linear e cinemática angular da marcha em pacientes com DPOC antes e após a participação em um Programa de Reabilitação Pulmonar. Métodos: Foram selecionadas avaliações da marcha de 16 sujeitos com DPOC ingressantes no Programa de Reabilitação Pulmonar da Universidade de Caxias do Sul (UCS). A análise cinemática da marcha foi realizada antes e após 12 semanas de participação neste programa. Resultados: Com relação às variáveis lineares da marcha, o comprimento do passo direito (p = 0,003), a cadência (p = 0,003), o tempo da passada direito e esquerdo (p = 0,003 e p = 0,006) e a velocidade (p = 0,013) apresentaram diferenças estatisticamente significativas. Já os aspectos angulares não apresentaram diferenças estatisticamente significativas entre as duas avaliações. Conclusão: O Programa de Reabilitação Pulmonar influenciou positivamente quase todos os parâmetros lineares da marcha, demonstrando a importância da interferência na marcha através de um tratamento adequado para a manutenção ou melhora da qualidade de vida destes indivíduos. (AU)

Introduction: The Chronic Obstructive Pulmonary Disease (COPD) is a respiratory disease that is related to functional impairment, and can cause gait modifications in these individuals. Objective: Analyze, from a database's information, the gait linear and angular kinematics parameters in COPD patients before and after participation in a pulmonary rehabilitation program. Methods: We selected gait analyses of 16 patients with COPD entrants in the University of Caxias do Sul Pulmonary Rehabilitation Program. The cinematic gait analysis was made before and after 12 weeks of this program. Results: About the gait linear parameters, the right step length (p = 0.003), the rhythm (p = 0.003, the right and left times length (p = 0.003 and p = 0.006) and the speed (p = 0.013) showed statistically significant differences. However, the angular aspects did not show statistically significant difference among the two evaluations. Conclusion: The pulmonary rehabilitation program positive influenced almost all the gait linear parameters, showing the importance of gait interference through appropriate treatment to maintenance or improvement of quality of life. (AU)