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Background: This study evaluated the effects of zein nanoparticles with resveratrol on neuroinflammation caused by Alzheimer's disease. Method: The sample consisted of 30 animals divided into control (C), positive control (CP), white nanoparticles (NB), resveratrol nanoparticles (NR) and resveratrol (R) groups. The animals received 10 mg/kg of resveratrol or nanoparticles according to the group, daily, for 15 days, oral administration. Afterward, they were submitted to immunohistochemical (IHC) analyses. Results: the IHC showed that there was no change in the morphological brain composition in the NR and C groups. Conversely, in the CP, NB, and R groups, changes in the deposition of Anti Tau were observed. The NR group showed a normal projection of taurine in the axon, which was not presented in the same way in the other groups. The CD68 marker showed no microglial activation in the R and C groups. Quantitative analyses of Anti Beta-Amyloid in the NR group showed a statistical difference com-pared to the CP, NB, and R groups, whereas the Anti Tau analysis showed a significant difference between the CP and NR groups. The CD68 marker showed a significant difference between the C and NR groups. The analysis of cy-tokines showed a significant difference in TNF-α between the C and CP groups, C and NB groups, CP and NR groups, and NB and NR groups. IL-6 and InF-δ showed no significant difference between all groups. IL-10 showed significant differences between the C and NR groups, C and R groups, and CP and NR groups. Conclusion: NR prevented the evolution of neuroinflammation(AU).

Introdução: Este estudo avaliou os efeitos das nanopartículas de zeína com resveratrol na neuroinflamação causada pela doença de Alzheimer. Método: A amostra consistiu em 30 animais divididos em grupos de controle (C), controle positivo (CP), nanopartículas brancas (NB), nanopartículas de resveratrol (NR) e resveratrol (R). Os animais receberam 10 mg/kg de resveratrol ou nanopartículas de acordo com o grupo, diariamente, por 15 dias, por via oral. Em seguida, foram submetidos a análises imuno-histoquímicas (IHC). Resultados: A IHC mostrou que não houve alteração na composição morfológica do cérebro nos grupos NR e C. Por outro lado, nos grupos CP, NB e R, foram observadas alterações na deposição de Anti Tau. O grupo NR mostrou uma projeção normal de taurina no axônio, que não se apresentou da mesma forma nos outros grupos. O marcador CD68 não mostrou ativação microglial nos grupos R e C. As análises quantitativas do antibeta-amiloide no grupo NR mostraram uma diferença estatística quando comparadas aos grupos CP, NB e R, enquanto a análise do antitau mostrou uma diferença significativa entre os grupos CP e NR. O marcador CD68 mostrou uma diferença significativa entre os grupos C e NR. A análise das citocinas mostrou uma diferença significativa no TNF-α entre os grupos C e CP, C e NB, CP e NR, e NB e NR. IL-6 e InF-δ não apresentaram diferença significativa entre todos os grupos. A IL-10 apresentou diferenças significativas entre os grupos C e NR, C e R, e CP e NR. Conclusão: A NR impediu a evolução da neuroinflamação (AU).

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Objective: Complex regional pain syndrome (CRPS) is usually triggered by trauma or a surgical procedure, and it typically becomes an established one after an intense inflammatory process with chronic pain and edema as the main symptoms. Available treatments for CRPS have low efficacy. This study aimed to evaluate the clinical and immunoregulatory effects of omega-3 polyunsaturated fatty acid (PUFA) supplementation on paw edema and anti- and pro-inflammatory cytokines and macrophage phenotypes in the chronic post-ischemia pain (CPIP) preclinical model of CRPS-Type I. Methods: Female Swiss mice were supplemented with omega-3, corn oil, or saline and then submitted to the CPIP model of ischemia/reperfusion (I/R) injury. Supplementation was carried out for 30 days prior to and up to 2 or 15 days after the induction of CPIP, according to experimental protocols. The supplementation protocol included 1,500 mg/kg of omega-3 or corn oil through an intragastric route (gavage). Paw edema, interleukin- (IL-) 4, IL-10, transforming growth factor-ß1 (TGF-ß1), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF) were then measured in the paw skin and muscle by enzyme-linked immunosorbent assay (ELISA), and macrophage phenotypes (M1 and M2) assessed in the paw muscle by Western blotting. Results: The CPIP model induced an increase in paw thickness up to 72 h post-I/R. Mice supplemented with omega-3 compared to the saline group displayed reduced edema but neither altered skin IL-4 or skin and muscle TGF-ß1, TNF, and MCP-1 concentrations, nor did they exhibit significantly altered muscle macrophage phenotype on the 2nd-day post-CPIP. However, omega-3 supplementation reversed the I/R-related reduction in IL-4 in the paw muscle compared to groups supplemented with saline and corn oil. Furthermore, omega-3 promoted the reduction of IL-10 levels in the paw skin, compared to animals with lesions supplemented with saline, until the 2nd-day post-CPIP. On the 15th day post-CPIP, IL-10 was significantly increased in the muscle of animals supplemented with omega-3 compared to the saline group. Conclusion: The results suggest that omega-3 PUFA supplementation has anti-inflammatory effects in the CPIP model of CRPS-Type I, significantly reducing paw edema and regulating concentrations of anti-inflammatory cytokines, including IL-4 and IL-10.

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Complex regional pain syndrome type I (CRPS-I) is a condition that responds poorly to treatments. The role of omega-3 fatty acids in the treatment of inflammatory disorders is well described in the literature; however, few studies have evaluated its therapeutic benefits in different types of pain. We evaluated the potential antihyperalgesic and anti-inflammatory effects of preventive omega-3 supplementation in an animal model of CRPS-I. In experiment 1, Swiss female mice were supplemented for 30 days with omega-3 before the induction of the CRPS-I model and 14 days after. Mechanical hyperalgesia was evaluated at baseline and from the 4th to the 14th day after CPRS-I induction along with open field locomotor activity after 30 days of supplementation. In experiment 2, Swiss female mice were supplemented for 30 days with omega-3 and then subjected to the CRPS-I model. Twenty-four hours later the animals were euthanized, and tissue samples of the spinal cord and right posterior paw muscle were taken to measure pro-inflammatory cytokine TNF and IL-1ß concentrations. Omega-3 supplementation produced antihyperalgesic and anti-inflammatory effects, as well as reducing pro-inflammatory cytokine concentrations, without altering the animals' locomotion. No open field locomotor changes were found. The 30-day supplementation at the tested dose was effective in the CRPS-I model.

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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.

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OBJECTIVE: Warm water immersion therapy (WWIT) has been widely used in the treatment of various clinical conditions, with analgesic and anti-inflammatory effects. However, its mechanism of action has not been fully investigated. The present study analyzed the role of spinal inhibitory neuroreceptors in the antihyperalgesic effect of WWIT in an experimental model of inflammatory pain. METHODS: Mice were injected with complete Freund's adjuvant (CFA; intraplantar [i.pl.]). Paw withdrawal frequency to mechanical stimuli (von Frey test) was used to determine: (1) the effect of intrathecal (i.t.) preadministration of naloxone (a non-selective opioid receptor antagonist; 5 µg/5 µl), (2); AM281 (a selective cannabinoid receptor type 1 [CB1] antagonist; 2 µg/5 µl), (3); and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; a selective adenosine A1 receptor antagonist; 10 nmol/5 µl), on the antihyperalgesic (pain-relieving) effect of WWIT against CFA-induced hyperalgesia. RESULTS: Intrathecal naloxone, AM281, and DPCPX significantly prevented the antihyperalgesic effect of WWIT. This study suggests the involvement of spinal (central) receptors in the antihyperalgesic effect of WWIT in a model of inflammatory pain. CONCLUSIONS: Taken together, these results suggest that opioid, CB1, and A1 spinal receptors might contribute to the pain-relieving effect of WWIT.

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In the last decades, balneotherapy or thermalism has been used for health promotion and in the treatment of inflammatory and chronic processes. We found that balneotherapy reduced mechanical hyperalgesia, as well the increase of BDNF and NOS2 levels in the spinal cord, while increased BDNF and NOS1 in the paw. The data presented herein demonstrated for the first time in a murine model of neuropathic pain, the analgesic effect of balneotherapy with the water from the natural springs of Santo Amaro da Imperatriz-Brazil. Nevertheless, future clinical trials should be conducted to test the effectiveness of balneotherapy in neuropathic pain patients.

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Cerebrovascular accident (CVA) is one of the leading causes of death and disability worldwide, as well as a major financial burden for health care systems. CVA rodent models provide experimental support to determine possible in vivo therapies to reduce brain injury and consequent sequelae. This study analyzed nociceptive, motor, cognitive and mood functions in mice submitted to distal middle cerebral artery (DMCA) occlusion. Male C57BL mice (n = 8) were randomly allocated to control or DMCA groups. Motor function was evaluated with the tests: grip force, rotarod and open field; and nociceptive threshold with von Frey and hot plate assessments. Cognitive function was evaluated with the inhibitory avoidance test, and mood with the tail suspension test. Evaluations were conducted on the seventh- and twenty-eighth-day post DMCA occlusion to assess medium- and long-term effects of the injury, respectively. DMCA occlusion significantly decreases muscle strength and spontaneous locomotion (p < 0.05) both medium- and long term; as well as increases immobility in the tail-suspension test (p < 0.05), suggesting a depressive-type behavior. However, DMCA occlusion did not affect nociceptive threshold nor cognitive functions (p > 0.05). These results suggest that, medium- and long-term effects of DMCA occlusion include motor function impairments, but no sensory dysfunction. Additionally, the injury affected mood but did not hinder cognitive function.

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As exercise intervention solely for pain reduction is relatively new, the available research still leaves an incomplete picture of responsible mechanisms and pathways. Nonetheless, evidence indicates that exercise-induced analgesia involves activation of the endocannabinoid (eCB) system. The present study investigated the role of the eCB system on the antihyperalgesic effect of high-intensity swimming exercise (HISE) in an animal model of peripheral persistent inflammation. Male Swiss mice were allocated to non-exercised and exercised groups and subjected to subcutaneous intraplantar injection (i.pl.) of a single dose of complete Freund's adjuvant (CFA) to induce inflammatory pain. Cumulative HISE was performed once a day, and mechanical hyperalgesia and edema were evaluated 0.5 hour after HISE for seven consecutive days. To investigate the role of the eCB system on the antihyperalgesic effect of HISE, non-exercised and exercised mice received intraperitoneal (ip), intrathecal (i.t.) or i.pl. injections of vehicle, AM281 (a CB1 cannabinoid receptor antagonist) or AM630 (a CB2 cannabinoid receptor antagonist) from the 3rd to 5th day after CFA injection. Mechanical hyperalgesia was evaluated 0.5 hour after HISE. In addition, the effect of the fatty acid amide hydrolase [FAAH] inhibitor or monoacylglycerol lipase [MAGL] inhibitor on the antihyperalgesic action of HISE was investigated. HISE reduced mechanical hyperalgesia with effects prevented by AM281 or AM630 pretreatment in all delivery routes tested. The inhibition of FAAH and MAGL prolonged the antihyperalgesic effect of HISE. These data demonstrate evidence for the role of the eCB system upon exercise-induced analgesia in a murine model of inflammatory pain.

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Transcranial photobiomodulation is an innovative method for the stimulation of neural activity which consists of the exposure of neural tissue to low-level light irradiance. In the present study, light-emitting diodes (LEDs) were used as light source due to their practicality and low cost. The objective was to analyze the effects of transcranial photobiomodulation using 945-nm LED in university students with anxiety and depression. Sample was composed of 22 individuals (17-25 years of age) divided into 2 groups of 11. LED group was treated with 945-nm LEDs for 1 min and 25 s (9.35 J/cm2), while in the placebo group, the device was off when placed in contact with the frontal bone for the same amount of time as in treatment group. Participants were evaluated at baseline and after 30 days with the hospital anxiety and depression scale (HADS), the faces test, the designs test, and the grip strength test. On the HADS for anxiety, the mean PAB, PAA, PhAB, and PhAA were 13.89 ± 3.55, 12.82 ± 3.18, 10.75 ± 2.49, and 6.66 ± 2.50 points, respectively. In the HADS for depression, the mean for the PDB group was 13.89 ± 3.55 points, in the PhDB group 12.82 ± 3.18 points, in the PDA group 10.75 ± 2.49 points, and in the PhDA group 6.66 ± 2.50 points. In the PA and PD groups, mean values of 8.0 ± 1.5 and 8.9 ± 1.26 scores were obtained, but did not reach significance; however, between PA and PhD analysis, a significance level of p = 0.0003 was obtained. The 945-nm LED transcranial photobiomodulation improves brain activity and may clinically decrease anxiety and depression.

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Lavandula angustifolia (LaEO) essential oil has been widely used by aromatherapy in the treatment of various clinical conditions, with evidence of its analgesic and anti-inflammatory potential. Our results demonstrate that sixty-five substances were identified in LaEO. Among the compounds found, the major ones were linalool (30.61%) and linalyl acetate (20.36%). We found that LaEO inhalation reduces mechanical hyperalgesia in conditions of chronic inflammatory and neuropathic pain. Furthermore, this effect seems to be mediated by peripheral and central opioid and cannabinoid 2 receptors. The findings of the present study suggests that the LaEO inhalation is effective on the chronic pain treatment.

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