RESUMO
BACKGROUND: An imbalance in the excitatory/inhibitory systems in the pain networks may explain the persistent chronic pain after hallux valgus surgery. Thus, to contra-regulate this dysfunction, the use of transcranial direct current stimulation (tDCS) becomes attractive. OBJECTIVE: We tested the hypothesis that two preoperative active(a)-tDCS sessions compared with sham(s)-tDCS could improve the postoperative pain [as indexed by Visual Analogue Scale (VAS) at rest and during walking (primary outcomes)]. To assess their effect on the change in the Numerical Pain Scale (NPS0-10) during Conditioned Pain Modulation (CPM-task), disability related to pain (DRP) and analgesic consumption (secondary outcomes). Also, we assessed if the brain derived neurotrophic factor (BDNF) in the cerebral spinal fluid (CSF) after tDCS could predict the intervention's effect on the DRP. METHODS: It is a prospective, double blind, sham-controlled, randomized single center, 40 women (18-70 years-old) who had undergone hallux valgus surgery were randomized to receive two sessions (20 minutes each) of anodal a-tDCS or s-tDCS on the primary motor cortex at night and in the morning before the surgery. To assess the DRP was used the Brazilian Profile of Chronic Pain: Screen (B-PCP:S). RESULTS: A-tDCS group showed lower scores on VAS at rest and during walking (P<0.001). At rest, the difference between groups was 2.13cm (95%CI = 1.59 to 2.68) while during walking was 1.67cm (95%CI = 1.05 to 2.28). A-tDCS, when compared to s-tDCS reduced analgesic doses in 73.25% (P<0.001), produced a greater reduction in B-PCP:S (mean difference of 9.41 points, 95%CI = 0.63 to 18.21) and higher function of descending pain modulatory system (DPMS) during CPM-task. CONCLUSION: A-tDCS improves postoperative pain, the DRP and the function of DPMS. Also, the CSF BDNF after a-tDCS predicted the improvement in the DRP. In overall, these findings suggest that a-tDCS effects may be mediated by top-down regulatory mechanisms associated with the inhibitory cortical control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02360462.
Assuntos
Hallux Valgus/cirurgia , Plasticidade Neuronal , Dor Pós-Operatória/terapia , Cuidados Pré-Operatórios , Estimulação Transcraniana por Corrente Contínua , Adulto , Fator Neurotrófico Derivado do Encéfalo/líquido cefalorraquidiano , Dor Crônica , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Dor Pós-Operatória/metabolismo , Estudos ProspectivosRESUMO
Exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-ß (Aß)1 - 42 diffuse plaques, and aggregated and hyperphosphorylated α-synuclein in olfactory nerves and key brainstem nuclei. We measured total prion protein (TPrP), total tau (T-tau), tau phosphorylated at threonine 181 (P-Tau), Aß1-42, α-synuclein (t-α-syn and d-α-synuclein), BDNF, insulin, leptin, and/or inflammatory mediators, in 129 normal CSF samples from MCMA and clean air controls. Aß1-42 and BDNF concentrations were significantly lower in MCMA children versus controls (pâ=â0.005 and 0.02, respectively). TPrP increased with cumulative PM2.5 up to 5 µg/m3 and then decreased, regardless of cumulative value or age (R2â=â0.56). TPrP strongly correlated with T-Tau and P-Tau, while d-α-synuclein showed a significant correlation with TNFα, IL10, and IL6 in MCMA children. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years (R2â=â0.47), while d-α-synuclein exhibited a tendency to increase with cumulated PM2.5 (R2â=â0.30). CSF Aß1-42, BDNF, α-synuclein, and TPrP changes are evolving in young MCMA urbanites historically showing underperformance in cognitive processes, odor identification deficits, downregulation of frontal cellular PrP, and neuropathological AD and PD hallmarks. Neuroprotection of young MCMA residents ought to be a public health priority.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/epidemiologia , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/epidemiologia , Material Particulado/efeitos adversos , População Urbana , Adolescente , Adulto , Poluição do Ar/efeitos adversos , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Fator Neurotrófico Derivado do Encéfalo/líquido cefalorraquidiano , Criança , Cidades/epidemiologia , Humanos , México/epidemiologia , Doença de Parkinson/diagnóstico , Fragmentos de Peptídeos/líquido cefalorraquidiano , Projetos Piloto , Estudos Prospectivos , Adulto Jovem , alfa-Sinucleína/líquido cefalorraquidianoRESUMO
Dexamethasone is widely used in the therapy of chronic inflammatory diseases for its pain-modulating effects. The objective of this study was to evaluate the effect of dexamethasone on nociception and local inflammation, and the levels of brain-derived neurotrophic factor (BDNF) in the spinal cord in male rats with chronic inflammation induced by complete Freund's adjuvant (CFA). Rats were randomly divided into a control group (not manipulated) and 2 CFA-induced chronic inflammation groups (in the 15th post-CFA injection): 1 injected with vehicle (saline solution) and 1 received dexamethasone (0.25 mg/kg) for 8 days. The hot-plate and electronic von Frey tests were performed 24 h after the end of treatment. BDNF spinal cord levels were determined by enzyme-linked immunosorbent assay (ELISA). The level of inflammation in the tibiotarsal joint (the ankle region) was evaluated histologically at the end of treatment. Dexamethasone produced significantly increased latency in the hot-plate test (one-way ANOVA, p < 0.05) and withdrawal threshold in the electronic von Frey test (p < 0.005). The dexamethasone group showed increased spinal cord BDNF levels compared to the other groups (one-way ANOVA p, < 0.05). Histological analysis showed a local inflammatory response only in animals treated with vehicle, which demonstrated that the dexamethasone treatment decreased the inflammatory process. Our findings corroborate the antinociceptive and anti-inflammatory properties of dexamethasone. In addition, we showed that the dexamethasone treatment increased BDNF levels in the spinal cord; its pain- modulating effects can be attributed to this effect.
Assuntos
Anti-Inflamatórios/farmacologia , Fator Neurotrófico Derivado do Encéfalo/líquido cefalorraquidiano , Dor/líquido cefalorraquidiano , Animais , Doença Crônica , Dexametasona/farmacologia , Ensaio de Imunoadsorção Enzimática , Adjuvante de Freund/toxicidade , Inflamação/líquido cefalorraquidiano , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF became a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have reported altered levels of BDNF in the circulation, i.e. serum or plasma, of patients with Alzheimer's disease (AD), and low BDNF levels in the CSF as predictor of future cognitive decline in healthy older subjects. Altered BDNF circulating levels have also been reported in other neurodegenerative and psychiatric disorders, hampering its use as a specific biomarker for AD. Therefore, BDNF seems to be an unspecific biomarker of neuropsychiatric disorders marked by neurodegenerative changes.
Assuntos
Doença de Alzheimer/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Animais , Biomarcadores , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator Neurotrófico Derivado do Encéfalo/líquido cefalorraquidiano , Fator Neurotrófico Derivado do Encéfalo/genética , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , RatosRESUMO
HTLV-1-associated myelopathy/tropical spastic paraparesis (TSP/HAM) is a chronic CNS disease characterized by axomyelinic degeneration of the long axons of corticospinal tracts. Levels of NGF, NT-3, NT-4/5, BDNF, GDNF, CNTF, and FGF-2 were measured in the cerebrospinal fluid (CSF) of 21 TSP/HAM patients and 20 controls. NGF, BDNF, and FGF-2 levels were also determined in 19 patients with HIV motor cognitive motor syndrome, and in 21 subjects diagnosed with Creutzfeldt Jakob disease (CJD). No significant differences were detected in the concentrations of NGF, BDNF, NT-3, NT-4/5, GDNF, and CNTF in the CSF between TSP/HAM patients and controls. FGF-2 was significantly lower in the CSF of the three groups of patients compared with controls; the HIV group exhibited the lowest values. HIV patients differed from TSP/HAM in their significantly higher levels of NGF and lower levels of BDNF and FGF-2, whereas CJD patients differed only in their higher levels of NGF. Immunohistochemical studies were done of trophic factors (NGF and FGF-2) and neurotrophin receptors (trkA and p75) in spinal cord and motor cortical areas from anatomopathological cases of TSP/HAM. Results indicated that NGF is expressed in motoneurons and oligodendrocytes of the posterior column of the spinal cord. FGF-2 was detected in motoneurons and spinal cord vessels. p75 receptor was detected in cortical neurons. The absence of a significant change in the trophic factor levels in TSP/HAM may be attributed to a selective axonal lesion in a slow process.