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Evidence suggests aerobic exercise has beneficial effects on cognitive performance in adults with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms might depend on mechanisms of exercise-mediated brain physiology. The study aims to investigate the effects of acute aerobic exercise on cortical excitability and cognitive performance, and the correlation between these phenomena in adults with ADHD. Twenty-six drug-naïve ADHD adults, and twenty-six age-, and gender-matched healthy controls were assessed with respect to cortical excitability and cognitive performance before and after acute aerobic exercise (a single session for 30 min) or a control intervention. The results show significantly enhanced intracortical facilitation (ICF) and decreased short intracortical inhibition (SICI) after aerobic exercise in healthy subjects. In contrast, SICI was significantly enhanced following acute aerobic exercise in ADHD. In ADHD, furthermore inhibitory control and motor learning were significantly improved after the acute aerobic exercise intervention. Alterations of SICI induced by aerobic exercise, and inhibitory control and motor learning improvement were significantly positively correlated in the ADHD group. Aerobic exercise had partially antagonistic effects in healthy controls, and ADHD patients. Furthermore, aerobic exercise-induced cognition-enhancing effects in ADHD depend on specific alterations of brain physiology, which differ from healthy humans.
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Transtorno do Deficit de Atenção com Hiperatividade , Cognição , Exercício Físico , Estimulação Magnética Transcraniana , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/reabilitação , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Masculino , Feminino , Exercício Físico/fisiologia , Adulto , Adulto Jovem , Cognição/fisiologia , Potencial Evocado Motor/fisiologia , Excitabilidade Cortical/fisiologia , EletromiografiaRESUMO
Previous studies have shown that aerobic exercise has beneficial effects on executive function in adolescents with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms could be partially due to aerobic exercise-induced cortical excitability modulation. The aim of this study was to explore the effects of acute aerobic exercise on executive functions and cortical excitability and the association between these phenomena in adolescents with ADHD. The study was conducted using a complete crossover design. Executive functions (inhibitory control, working memory, and planning) and cortical excitability were assessed in twenty-four drug-naïve adolescents with ADHD before and after acute aerobic exercise or a control intervention. Inhibitory control, working memory, and planning improved after acute aerobic exercise in adolescents with ADHD. Moreover, cortical excitability monitored by transcranial magnetic stimulation (TMS) decreased after intervention in this population. Additionally, improvements in inhibitory control and working memory performance were associated with enhanced cortical inhibition. The findings provide indirect preliminary evidence for the assumption that changes in cortical excitability induced by aerobic exercise partially contribute to improvements in executive function in adolescents with ADHD.
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PURPOSE: This population-based cohort study aimed to examine the association with childhood attention deficit/hyperactivity disorder (ADHD) and bullying experiences during adolescence among Digital Generation individuals, exploring both traditional and cyberbullying. METHODS: This study included data from 15,240 participants, collected from the Taiwan Adolescent to Adult Longitudinal Study project. Participants, initially in seventh and 10th grade in 2015, were selected through a multistage stratified sampling approach. Self-report questionnaires assessed traditional and cyberbullying victimization experiences during adolescence, with 5-year longitudinal follow-up. Childhood ADHD diagnoses were identified by linking data to Taiwan's National Health Insurance Research Database from 2000 to 2015. Logistic regression models were employed to examine the relationship between childhood ADHD and bullying victimization while controlling for relevant covariates. RESULTS: Individuals diagnosed with childhood ADHD exhibited a significantly higher likelihood of experiencing bullying during adolescence (adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.28-1.80). This association extended to various forms of bullying, including physical (aOR = 1.42, 95% CI: 1.20-1.68), verbal (aOR = 1.42, 95% CI: 1.20-1.67), relational (aOR = 1.45, 95% CI: 1.22-1.71), and cyber (aOR = 1.35, 95% CI: 1.14-1.61). Additional factors positively associated with bullying victimization included male, binge drinking, and depression, while a positive campus atmosphere was protective against bullying. However, there is no evidence for interactions between these factors and ADHD in their associations with bullying. DISCUSSION: Childhood ADHD increases the risk of both traditional and cyberbullying during adolescence. Recognizing this risk is essential for targeted interventions and further research on underlying mechanisms.
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Transtorno do Deficit de Atenção com Hiperatividade , Bullying , Vítimas de Crime , Cyberbullying , Humanos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Masculino , Feminino , Cyberbullying/psicologia , Cyberbullying/estatística & dados numéricos , Vítimas de Crime/estatística & dados numéricos , Vítimas de Crime/psicologia , Taiwan/epidemiologia , Estudos Longitudinais , Bullying/psicologia , Bullying/estatística & dados numéricos , Inquéritos e Questionários , Autorrelato , Estudos de Coortes , CriançaRESUMO
This study employs a bivariate EGARCH model to examine the Taiwan Futures Exchange's regular and after-hours trading, focusing on the critical aspects of spillover and expiration effects, as well as volatility clustering and asymmetry. The objective of this study is to observe the impact on the trading sessions in Taiwan by the influences of the European and American markets, focusing on the essential roles of the price discovery function and risk disclosure effectiveness of the regular hours trading. This research is imperative considering the increasing interconnectedness of global financial markets and the need for comprehensive risk assessment for investment strategies. It also examines the hedging behavior of after-hours traders, thereby aiming to contribute to pre-investment analysis by future investors. This examination is vital for understanding the dynamics of after-hours trading and its influence on market stability. Results indicate price continuity between both trading sessions, with regular trading often determining after-hours price ranges. Consequently, after-hours price changes can inform regular trading decisions. This finding highlights the importance of after-hours trading for shaping market expectations. Significant profit potential exists in after-hours trading open interest, which serves speculative and hedging purposes. While regular trading volatility influences after-hours trading, the reverse is not true. This suggests Taiwan market information poses a higher risk impact than European and American market data, emphasizing the unique position of the Taiwan market in the global financial ecosystem. After-hours trading volatility reflects the absorption of international market information and plays a crucial role in advance revelation of risks. This underscores the importance of after-hours trading in global risk management and strategy formulation.
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Ecossistema , Investimentos em Saúde , Previsões , Gestão de Riscos , TaiwanRESUMO
Pain is an unpleasant sensory and emotional experience accompanied by tissue injury. Often, an individual's experience can be influenced by different physiological, psychological, and social factors. Fibromyalgia, one of the most difficult-to-treat types of pain, is characterized by general muscle pain accompanied by obesity, fatigue, sleep, and memory and psychological concerns. Fibromyalgia increases nociceptive sensations via central sensitization in the brain and spinal cord level. We used intermittent cold stress to create a mouse fibromyalgia pain model via a von Frey test (day 0: 3.69 ± 0.14 g; day 5: 2.13 ± 0.12 g). Mechanical pain could be reversed by eicosapentaenoic acid (EPA) administration (day 0: 3.72 ± 0.14 g; day 5: 3.69 ± 0.13 g). A similar trend could also be observed for thermal hyperalgesia. The levels of elements in the transient receptor potential V1 (TRPV1) signaling pathway were increased in the ascending pain pathway, including the thalamus, medial prefrontal cortex, somatosensory cortex, anterior cingulate cortex, and cerebellum. EPA intake significantly attenuated this overexpression. A novel chemogenetics method was used to inhibit SSC and ACC activities, which presented an analgesic effect through the TRPV1 downstream pathway. The present results provide insights into the role of the TRPV1 signaling pathway for fibromyalgia and its potential as a clinical target.
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Fibromialgia , Animais , Camundongos , Encéfalo , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Fibromialgia/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , DorRESUMO
BACKGROUND: This study aimed to investigate the effects of different aerobic exercise intensities on inhibitory control and cortical excitability in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: The study was conducted in a within-subject design. Twenty-four adults with ADHD completed a stop signal task and received cortical excitability assessment by transcranial magnetic stimulation (TMS) before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. RESULTS: Acute moderate-, and high-intensity aerobic exercise improved inhibitory control in adults with ADHD. Moreover, the improving effect was similar between moderate-, and high-intensity aerobic exercise conditions. As shown by the brain physiology results, short interval intracortical inhibition was significantly increased following both, moderate- and high-intensity aerobic exercise intervention conditions. Additionally, the alteration of short interval intracortical inhibition and inhibitory control improvement were positively correlated. CONCLUSIONS: The moderate-, and high-intensity aerobic exercise-dependent alterations of cortical excitability in adults with ADHD might partially explain the inhibitory control-improving effects of aerobic exercise in this population.
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Transtorno do Deficit de Atenção com Hiperatividade , Excitabilidade Cortical , Exercício Físico , Inibição Psicológica , Estimulação Magnética Transcraniana , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Masculino , Adulto , Feminino , Estimulação Magnética Transcraniana/métodos , Exercício Físico/fisiologia , Adulto Jovem , Excitabilidade Cortical/fisiologia , Potencial Evocado Motor/fisiologia , Inibição Neural/fisiologia , Terapia por Exercício/métodos , Córtex Motor/fisiopatologiaRESUMO
Neuropathic pain, which is initiated by a malfunction of the somatosensory cortex system, elicits inflammation and simultaneously activates glial cells that initiate neuroinflammation. Electroacupuncture (EA) has been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We suggest that EA can reliably cure neuropathic disease through anti-inflammation and transient receptor potential V1 (TRPV1) signaling pathways from the peripheral to the central nervous system. To explore this, we used EA to treat the mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetics techniques. Both mechanical and thermal pain were found in SNI mice at four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Mechanical hyperalgesia was partially attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g), and thermal hyperalgesia was fully reduced (thermal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), suggesting EA's specificity. In addition, animals with Trpv1 deletion showed partial mechanical hyperalgesia and no significant induction of thermal hyperalgesia in neuropathic pain mice (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-ß), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in the EA and Trpv1-/- groups rather than the sham group. Western blot and immunofluorescence analysis showed similar tendencies in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity, which showed an analgesic effect through the TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as a beneficial target for neuropathic pain.
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Eletroacupuntura , Neuralgia , Traumatismos do Sistema Nervoso , Ratos , Camundongos , Animais , Hiperalgesia/etiologia , Hiperalgesia/terapia , Hiperalgesia/metabolismo , Eletroacupuntura/métodos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Neuralgia/etiologia , Neuralgia/terapia , Neuralgia/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , Transdução de Sinais , Traumatismos do Sistema Nervoso/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
An accurate method is proposed to deal with such nonadiabatic transitions as those energetically inaccessible, namely, classically forbidden transitions. This is formulated by using the corresponding Zhu-Nakamura formulas and finding the optimal paths in the classically forbidden tunneling regions that maximize the overall transition probabilities. This can be done for both the nonadiabatic tunneling type (so-called normal case in electron transfer) in which two diabatic potentials have opposite signs of slopes and the Landau-Zener type (inverted case) in which two diabatic potentials have the same sign of slopes. The method is numerically demonstrated to be useful for clarifying chemical and biological dynamics.
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Converging evidence indicates the beneficial effects of aerobic exercise on motor learning performance. Underlying mechanisms might be an impact of aerobic exercise on neuroplasticity and cortical excitability. Evidence suggests that motor learning and cortical excitability alterations correlate with the intensity of aerobic exercise and the activity level of participants. Thus, this study aims to investigate the effects of different aerobic exercise intensities on motor learning and cortical excitability in sedentary individuals. The study was conducted in a crossover and double-blind design. Twenty-six healthy sedentary individuals (13 women and 13 men) performed a motor learning task and received a cortical excitability assessment before and after a single session of low-, moderate-, and high-intensity aerobic exercise or a control intervention. The study revealed that motor learning performance and cortical excitability were significantly enhanced in the moderate-intensity aerobic exercise, compared with the other conditions. These findings suggest aerobic exercise intensity-dependent effects on motor learning in sedentary adults. The underlying mechanism might be an exercised-induced alteration of cortical excitability, specifically a reduction of GABA activity.
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Excitabilidade Cortical , Córtex Motor , Adulto , Feminino , Humanos , Masculino , Potencial Evocado Motor , Exercício Físico , Estimulação Magnética Transcraniana , Estudos Cross-Over , Método Duplo-CegoRESUMO
Plastic particles are found almost ubiquitously in the environment and can get ingested orally by humans. We have used food-relevant microplastics (2 µm polylactic acid), submicroplastics (250 nm polylactic acid and 366 nm melamine formaldehyde resin) and nanoplastics (25 nm polymethylmethacrylate) to study material- and size-dependent uptake and transport across the human intestinal barrier and liver. Therefore, different Transwell™-based in vitro (co-)culture models were used: Differentiated Caco-2 cells mimicking the intestinal enterocyte monolayer, an M-cell model complementing the Caco-2 monoculture with antigen uptake-specialized cells, a mucus model complementing the barrier with an intestinal mucus layer, and an intestinal-liver co-culture combining differentiated Caco-2 cells with differentiated HepaRG cells. Using these complex barrier models, uptake and transport of particles were analyzed based on the fluorescence of the particles using confocal microscopy and a fluorescence-based quantification method. Additionally, the results were verified by Time-of-Flight - Secondary Ion Mass Spectrometry (ToF-SIMS) analysis. Furthermore, an effect screening at the mRNA level was done to investigate oxidative stress response, inflammation and changes to xenobiotic metabolism in intestinal and hepatic cells after exposure to plastic particles. Oxidative stress and inflammation were additionally analyzed using a flow-cytometric assay for reactive oxygen species and cytokine measurements. The results reveal a noteworthy uptake into and transport of microplastic and submicroplastic particles across the intestinal epithelium. Particularly, we show a pronounced uptake of particles into liver cells after crossing of the intestinal epithelium, using the intestinal-liver co-culture. The particles evoke some alterations in xenobiotic metabolism, but did not cause increased oxidative stress or inflammatory response on protein level. Taken together, these complex barrier models can be applied on micro-, submicro- and nanoplastics and reveal information in particle uptake, transport and cellular impact.
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Microplásticos , Plásticos , Humanos , Microplásticos/toxicidade , Células CACO-2 , Xenobióticos , Fígado , InflamaçãoRESUMO
BACKGROUND: Chronic pain refers to pain that persists for over three months. Chronic pain may restrict activities of daily living, including work, learning, social life, and can lead to anxiety, depression, and sleep disturbance. Imaging data have demonstrated that central sensitization often occurs in the brain of patients with chronic pain, which arises from imbalanced neurotransmission in the central nervous system. Transient receptor potential vanilloid 1 (TRPV1) is an ion channel to serve as an inflammatory detector in the brain. We aim to determine the properties of acupoint catgut embedding (ACE) on cold stress-induced mice fibromyalgia (FM) and surveyed the character of TRPV1 and linked molecules in chronic FM pain. METHODS: Intermittent cold stress (ICS) was used to induce mice FM model. Mice were subgrouped into normal mice, ICS-induced FM group, FM mice with ACE, and FM in Trpv1-â£/- group. ACE is a novel acupuncture technique that provides convenience and continuous nerve stimulation that has been reported effective on pain management. RESULTS: Our behavioral experiments showed similar levels of pain response among all groups before treatment. After ICS, prolonged mechanical and thermal pain was initiated (mechanical threshold: 1.96 ± 0.12 g; thermal latency: 4.86 ± 0.21 s) and were alleviated by ACE treatment and TRPV1 gene deletion. Inflammatory mediators were increased in the plasma of FM mice, while TRPV1 and related kinases were amplified in the hypothalamus and cerebellum. These changes were ameliorated in the ACE-treated and Trpv1-â£/- groups. CONCLUSIONS: These novel findings suggest that chronic FM pain can be modulated by ACE or TRPV1 gene deletion. The analgesic effect of ACE through the TRPV1 pathway may reflect its potential as a therapeutic target for FM treatment.
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Dor Crônica , Fibromialgia , Animais , Camundongos , Atividades Cotidianas , Pontos de Acupuntura , Encéfalo/metabolismo , Categute , Fibromialgia/tratamento farmacológico , Fibromialgia/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
Acute myeloid leukemia (AML) is a fast-growing and highly fatal blood cancer, and recent research has shown that targeting metabolism may be a promising therapeutic approach for treating AML. One promising target is the human mitochondrial NAD(P)+-dependent malic enzyme (ME2), which is involved in the production of pyruvate and NAD(P)H and the regulation of the NAD+/NADH redox balance. Inhibition of ME2 via silencing ME2 or utilizing its allosteric inhibitor disodium embonate (Na2EA) causes a decrease in pyruvate and NADH, leading to a decrease in producing ATP via cellular respiration and oxidative phosphorylation. ME2 inhibition also decreases NADPH levels, resulting in an increase in reactive oxygen species (ROS) and oxidative stress, which ultimately leads to cellular apoptosis. Additionally, ME2 inhibition reduces pyruvate metabolism and the biosynthetic pathway. ME2 silencing inhibits the growth of xenotransplanted human AML cells, and the allosteric ME2 inhibitor Na2EA demonstrates antileukemic activity against immune-deficient mice with disseminated AML. Both of these effects are a result of impaired energy metabolism in mitochondria. These findings suggest that the targeting ME2 may be an effective strategy for treating AML. Overall, ME2 plays an essential role in energy metabolism of AML cells, and its inhibition may offer a promising approach for AML treatment.
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Leucemia Mieloide Aguda , NAD , Humanos , Camundongos , Animais , NAD/metabolismo , Linhagem Celular Tumoral , Metabolismo Energético , Oxirredução , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , PiruvatosRESUMO
Background: Evidence indicates beneficial effects of aerobic exercise on motor learning performance, which might be caused by the impact of aerobic exercise on cortical excitability. It is thus suggested that physiological effects of aerobic exercise on cortical excitability determine the effects of aerobic exercise on motor learning. Nevertheless, respective results usually come from independent studies, and a prove of the causal relationship between neurophysiological and motor learning effects is still missing. This study aims to explore the impact of a single bout of aerobic exercise on brain physiology and motor learning, and the association between these phenomena in humans Method: The study was conducted in a cross-over design. In twenty healthy subjects, cortical excitability and motor learning were assessed before and after a single bout of aerobic exercise or a control intervention Results: The results show that aerobic exercise improved motor sequence learning and enhanced cortical excitability in humans. Furthermore, a correlation between the exercise-dependent alteration of cortical excitability (short intracortical inhibition, which is determined primarily by the GABAergic system) and improvement of motor learning has been found Discussion: The study found motor learning performance-improving effects of aerobic exercise, and these results might be explained by an exercised-caused alteration of cortical excitability, especially a reduction of GABA activity. (AU)
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Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Atividade Motora , Exercício Físico , Excitabilidade Cortical , Estudos Cross-Over , GABAérgicos , não FumantesRESUMO
Background: Evidence indicates beneficial effects of aerobic exercise on motor learning performance, which might be caused by the impact of aerobic exercise on cortical excitability. It is thus suggested that physiological effects of aerobic exercise on cortical excitability determine the effects of aerobic exercise on motor learning. Nevertheless, respective results usually come from independent studies, and a prove of the causal relationship between neurophysiological and motor learning effects is still missing. This study aims to explore the impact of a single bout of aerobic exercise on brain physiology and motor learning, and the association between these phenomena in humans. Method: The study was conducted in a cross-over design. In twenty healthy subjects, cortical excitability and motor learning were assessed before and after a single bout of aerobic exercise or a control intervention. Results: The results show that aerobic exercise improved motor sequence learning and enhanced cortical excitability in humans. Furthermore, a correlation between the exercise-dependent alteration of cortical excitability (short intracortical inhibition, which is determined primarily by the GABAergic system) and improvement of motor learning has been found. Discussion: The study found motor learning performance-improving effects of aerobic exercise, and these results might be explained by an exercised-caused alteration of cortical excitability, especially a reduction of GABA activity.
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Spontaneous intracranial hypotension (SIH) is a poorly understood condition that presents with a wide variety of symptoms, ranging from mild headaches to coma. It is typically caused by continuous spontaneous leakage of spinal cerebrospinal fluid (CSF), resulting in orthostatic headaches. However, the appropriate management of refractory SIH remains unclear. A 50-year-old man presented with orthostatic headache followed by a rapid decline in mental status. The imaging findings were consistent with the diagnosis of SIH, with bilateral cerebral subdural hematomas and abnormal fluid collection in the posterior epidural space from the T2 to T12 levels. Computed tomography myelography of the whole spine revealed multiple high-flow CSF leakages at the T6 to T8 levels. Despite treatment with bilateral burr hole drainage for subdural hematomas and repeated lumbar epidural blood patch (EBP) three times, the patient's condition worsened and he developed stupor. A lumbar intrathecal saline bolus (90 ml) was administered to restore CSF depletion. The patient's verbal function improved immediately, and continuous intrathecal saline infusion was administered at a rate of 10 ml/h for two days. The patient's stupor gradually resolved, and after his symptoms improved, the EBP injection was repeated at the T8 level. The patient recovered completely, and during the six-year follow-up, there were no signs of recurrence. SIH may cause a refractory decline in mental status, and lumbar intrathecal saline infusion may help arrest or reverse an impending central (transtentorial) herniation. This case demonstrates an appropriate bolus and continuous infusion of normal saline, and documents the resolution of SIH. This maneuver may change the CSF flow pattern and aims to seal the CSF fistula. Further studies are needed to better understand the mechanism of intrathecal saline infusion and establish effective treatment strategies for refractory cases of SIH.
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(1) Background: The medical practice of acupuncture involves the insertion of a specialized stainless needle into a specific body point, often called an acupoint, to initiate a perceived phenomenon of de-qi sensation. Therefore, the term "de-qi" describes bodily sensations experienced by the recipient during acupuncture, which may include feelings of soreness, heaviness, fullness, numbness, and migration. However, while acupuncture treatments reportedly result in acupoint activation and an increased release of neurotransmitters or cytokines, detecting these substances released into the acupoint microenvironment is often missed or delayed in clinical and basic practice. (2) Methods: To address this situation, we employed a paper-based enzyme-linked immunosorbent assay method to examine acupoint environmental changes using minute volumes of easily accessible acupoint fluids. (3) Results: Our results indicated that while levels of adenosine triphosphate (ATP), interleukin-1ß, interleukin-6, glutamate, substance P, and histamine were all increased in the experimental group following electroacupuncture (EA) treatment, contrary results were observed in the sham EA and transient receptor potential vanilloid 1 (Trpv1-/-) groups. Subsequently, TRPV1 and its associated molecules were augmented in mouse dorsal root ganglion, spinal cord, thalamus, and the somatosensory cortex, then examined by Western blotting and immunofluorescence techniques. Investigations revealed that these elevations were still unobserved in the sham EA or EA in the Trpv1-/- groups. Furthermore, results showed that while administering ATP could mimic EA function, it could be reversed by the ATP P2 receptor antagonist, suramin. (4) Conclusions: Our data provide novel information, indicating that changes in neurotransmitter and cytokine levels can offer insight into acupuncture mechanisms and clinical targeting.
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Pontos de Acupuntura , Citocinas , Animais , Camundongos , Trifosfato de Adenosina , Ácido Glutâmico , Histamina , Interleucina-1beta , Interleucina-6 , Neurotransmissores , Substância P , SuraminaRESUMO
Peripheral tissue damage and associated inflammation can trigger neuroplastic changes in somatic pain pathways, such as reduced neuronal firing thresholds and synaptic potentiation, that ultimately lead to peripheral sensitization and chronic pain. Electroacupuncture (EA) can relieve chronic inflammatory pain, but the underlying mechanisms are unknown, including the contributions of higher pain centers such as somatosensory cortex (SSC). We investigated these mechanisms using optogenetic modulation of SSC activity in a mouse inflammatory pain model. Injection of Complete Freund's Adjuvant into the hind paw reliably induced inflammation accompanied by reduced mechanical and thermal pain thresholds (hyperalgesia) within three days (mechanical: 1.54 ± 0.13 g; thermal: 3.94 ± 0.43 s). Application of EA produced significant thermal and mechanical analgesia, but these responses were reversed by optogenetic activation of SSC neurons, suggesting that EA-induced analgesia involves modulation of central pain pathways. Western blot and immunostaining revealed that EA also attenuated CaMKIIα signaling in the dorsal root ganglion, central spinal cord, SSC, and anterior cingulate cortex (ACC). In contrast, optogenetic activation of the SSC induced CaMKIIα signaling in SSC and ACC. These findings suggest that AE can relieve inflammatory pain by suppressing CaMKIIα-dependent plasticity in cortical pain pathways. The SSC and ACC CaMKIIα signaling pathways may be valuable therapeutic targets for chronic inflammatory pain treatment.
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Agnosia , Eletroacupuntura , Animais , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/terapia , Camundongos , Optogenética , Dor/metabolismo , Manejo da DorRESUMO
Fibromyalgia is characterized by chronic and persistent widespread pain and generalized muscle tenderness, and it is refractory to treatment. The central nervous system (CNS) plays an important role, pain signalling, in fibromyalgia subjects. Electroacupuncture (EA) has been practiced for thousand years to treat many diseases that involve pain. We established fibromyalgia-like pain in mice using intermittent cold stress and investigated therapeutic effects and modes of action with EA. EA of 2 Hz and 1 mA was performed for 20 min at the ST36 acupoint in mice from Day 3 to Day 5. Our results showed that mechanical and thermal hyperalgesia were induced by intermittent cold stress (Day 5: mechanical: 1.43 ± 0.34 g; thermal: 3.98 ± 0.73 s) and were subsequently reversed by EA (Day 5: mechanical: 4.62 ± 0.48 g; thermal: 7.68 ± 0.68 s) or Trpv1 -/- (Day 5: mechanical: 4.38 ± 0.51 g; thermal: 7.48 ± 0.98 s). Activity in the HMGB1, S100B, and TRPV1 pathways was increased in the mouse prefrontal cortex, somatosensory cortex, thalamus, and amygdala with the stress treatment. This increase was attenuated by EA or Trpv1 -/-. These results suggest potential targets for the treatment of TRPV1-dependant fibromyalgia pain.