Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

Impact of multiple-session home-based transcranial direct current stimulation (M-HB-tDCS) on eating behavior in fibromyalgia: A factorial randomized clinical trial.

BACKGROUND: Multiple-session home-based self-applied transcranial direct current stimulation (M-HB-self-applied-tDCS) has previously been found to effectively reduce chronic pain and enhance cognitive function. However, the effectiveness of this method for disordered eating behavior still needs to be studied. OBJECTIVE: This study aimed to assess whether 20 sessions of M-HB-self-applied-tDCS, administered over four weeks to either the left dorsolateral prefrontal cortex (L-DLPFC) or primary motor cortex (M1), could improve various aspects of eating behavior, anthropometric measures, and adherence. METHODS: We randomly assigned 102 fibromyalgia patients between the ages of 30 and 65 to one of four tDCS groups: L-DLPFC (anodal-(a)-tDCS, n = 34; sham-(s)-tDCS, n = 17) or M1 (a-tDCS, n = 34; s-tDCS, n = 17). Patients self-administered 20-min tDCS sessions daily with 2 mA under remote supervision following in-person training. RESULTS: Generalized linear models revealed significant effects of M-HB-self-applied-tDCS compared to s-tDCS on uncontrolled eating (UE) (Wald χ2 = 5.62; df = 1; P = 0.018; effect size, ES = 0.55), and food craving (Wald χ2 = 5.62; df = 1; P = 0.018; ES = 0.57). Regarding fibromyalgia symptoms, we found a differentiated impact of a-tDCS on M1 compared to DLPFC in reducing food cravings. Additionally, M-HB-a-tDCS significantly reduced emotional eating and waist size. In contrast, M1 stimulation was more effective in improving fibromyalgia symptoms. The global adherence rate was high, at 88.94%. CONCLUSION: These findings demonstrate that M-HB-self-applied-tDCS is a suitable approach for reducing uncontrolled and emotional eating, with greater efficacy in L-DLPFC. Furthermore, these results revealed the influence of fibromyalgia symptoms on M-HB-self-applied-tDCS's, with M1 being particularly effective in mitigating food cravings and reducing fibromyalgia symptoms.

High-beta oscillations at EEG resting state and hyperconnectivity of pain circuitry in fibromyalgia: an exploratory cross-sectional study.

Background: Electroencephalography (EEG) has identified neural activity in specific brain regions as a potential indicator of the neural signature of chronic pain. This study compared the lagged coherence connectivity between regions of interest (ROIs) associated with the pain connectome in women with fibromyalgia (FM) and healthy women (HC). Methods: We evaluated 64 participants (49 FM and 15 HC) during resting-state EEG sessions under both eyes open (EO) and eyes closed (EC) conditions. In addition to EEG measurements, we assessed clinical and psychological symptoms and serum levels of brain-derived neurotrophic factor (BDNF). The connectivity between eight ROIs was computed across eight different EEG frequencies. Results: The FM group demonstrated increased connectivity between the left dorsolateral prefrontal cortex (DLPFC) and right anterior cingulate cortex (ACC), specifically in the beta-3 frequency band (t = 3.441, p = 0.044). When comparing the EO and EC conditions, FM patients exhibited heightened interhemispheric connectivity between insular areas (t = 3.372, p = 0.024) and between the left insula (INS) and right DLPFC (t = 3.695, p = 0.024) within the beta-3 frequency band. In the EC condition, there was a negative correlation between pain disability and connectivity in the beta-3 frequency band between the left ACC and the left primary somatosensory cortex (SI; r = -0.442, p = 0.043). In the EO condition, there was a negative correlation between central sensitization severity and lagged coherence connectivity in the alpha-2 frequency band between the right ACC and left SI (r = 0.428, p = 0.014). Moreover, in the EO-EC comparison, the lagged coherence connection between the left DLPFC and right INS, indexed by the gamma frequency band, showed a negative correlation with serum BDNF levels (r = -0.506, p = 0.012). Conclusion: These findings indicate that increased connectivity between different pain processing circuits, particularly in the beta-3 frequency band during rest, may serve as neural biomarkers for the chronic pain brain signature associated with neuroplasticity and the severity of FM symptoms.

Preemptive transcranial direct current stimulation induces analgesia, prevents chronic inflammation and fibrosis, and promotes tissue repair in a rat model of postoperative pain.

This study evaluated the effects of previous exposure to Transcranial Direct Current Stimulation (tDCS) on nociceptive, neuroinflammatory, and neurochemical parameters, in rats subjected to an incisional pain model. Forty adult male Wistar rats (60 days old; weighing âˆ¼ 250 g) were divided into five groups: 1. control (C); 2. drugs (D); 3. surgery (S); 4. surgery + sham-tDCS (SsT) and 5. surgery + tDCS (ST). Bimodal tDCS (0.5 mA) was applied for 20 min/day/8 days before the incisional model. Mechanical allodynia (von Frey) was evaluated at different time points after surgery. Cytokines and BDNF levels were evaluated in the cerebral cortex, hippocampus, brainstem, and spinal cord. Histology and activity of myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAGase) were evaluated in the surgical lesion sites in the right hind paw. The results demonstrate that the surgery procedure increased BDNF and IL-6 levels in the spinal cord levels in the hippocampus, and decreased IL-1ß and IL-6 levels in the cerebral cortex, IL-6 levels in the hippocampus, and IL-10 levels in the brainstem and hippocampus. In addition, preemptive tDCS was effective in controlling postoperative pain, increasing BDNF, IL-6, and IL-10 levels in the spinal cord and brainstem, increasing IL-1ß in the spinal cord, and decreasing IL-6 levels in the cerebral cortex and hippocampus, IL-1ß and IL-10 levels in the hippocampus. Preemptive tDCS also contributes to tissue repair, preventing chronic inflammation, and consequent fibrosis. Thus, these findings imply that preemptive methods for postoperative pain management should be considered an interesting pain management strategy, and may contribute to the development of clinical applications for tDCS in surgical situations.

Transcranial Direct Current Stimulation (tDCS) Promotes state-dependent Effects on Neuroinflammatory and Behavioral Parameters in rats Chronically Exposed to Stress and a Hyper-Palatable Diet.

Chronic stress is a common condition affecting health, often associated with unhealthy eating habits. Transcranial direct current stimulation (tDCS) has been proposed to address these issues. Thus, this research investigated the effects of tDCS on biometric, behavioral, and neurochemical parameters in chronically stressed rats fed a hyper-palatable cafeteria diet (CAFD). The study lasted 8 weeks, with CAFD exposure and/or chronic restraint stress model (CRS - 1 h/day, 5 days/week, for 7 weeks) started concurrently. tDCS or sham sessions were applied between days 42 and 49 (0.5 mA, 20 min/day). CAFD increased body weight, caloric consumption, adiposity, and liver weight. It also altered central parameters, reducing anxiety and cortical levels of IL-10 and BDNF. In turn, the CRS resulted in increased adrenals in rats with standard diet (SD), and anxiety-like and anhedonic behaviors in rats with CAFD. tDCS provided neurochemical shifts in CAFD-fed stressed rats increasing central levels of TNF-α and IL-10, while in stressed rats SD-fed induced a decrease in the adrenals weight, relative visceral adiposity, and serum NPY levels. These data demonstrated the anxiolytic effect of CAFD and anxiogenic effect of stress in CAFD-fed animals. In addition, tDCS promoted state-dependent effects on neuroinflammatory and behavioral parameters in rats chronically exposed to stress and a hyper-palatable diet. These findings provide primary evidence for additional mechanistic and preclinical studies of the tDCS technique for stress-related eating disorders, envisioning clinical applicability.

Nicotinamide riboside and dietary restriction effects on gut microbiota and liver inflammatory and morphologic markers in cafeteria diet-induced obesity in rats.

OBJECTIVES: No specific therapy is available for metabolic dysfunction-associated fatty liver disease. We investigated nicotinamide riboside (NR) and dietary restriction (DR) effects in liver lipids, inflammation, histology, intestinal permeability, and gut microbiota in a cafeteria diet (CAFD)-induced obesity model. METHODS: Adult male Wistar rats were randomly assigned to standard diet (SD) or CAFD. After 6 wk, they were subdivided into six groups-SD + vehicle (Veh) (distilled water), SD + NR (400 mg/kg), DR + Veh, DR + NR, CAFD + Veh, and CAFD + NR-for 4 wk more until euthanasia. RESULTS: CAFD increased the hepatic content of lipids, triacylglycerols, and total cholesterol and promoted hepatomegaly, steatosis, steatohepatitis, and liver fibrosis. DR intervention successfully delayed the onset of CAFD-induced liver abnormalities except for steatosis and fibrosis. CAFD suppressed Sirt1 expression in the liver and DR increased Sirt3 expression. CAFD did not affect hepatic inflammatory genes but DR enhanced Il10 expression while decreasing Il1ß expression. CAFD reduced Firmicutes and increased Bacteroidetes and Cyanobacteria, with no changes in intestinal permeability. Gut microbiota patterns in animals exposed to DR were similar to those of animals in SD. NR, specifically in CAFD, reduced hepatic triacylglycerols and total cholesterol deposition and collagen fiber accumulation in the liver and limited the colonization of CAFD-induced Cyanobacteria. NR combined with DR decreased the liver's relative weight and Tnfα expression and suppressed Sirt1 and Sirt3 hepatic expression. CONCLUSIONS: This study suggests that NR can be a potential adjuvant to metabolic dysfunction-associated fatty liver disease therapy, encouraging further research in this field.

The Application of Static Magnetic Stimulation Reduces Survival of SH-SY5Y Neuroblastoma Cells.

BACKGROUND/AIM: Central nervous system cancer is still a major public health issue. The effectiveness of treatments is limited and varies depending on the severity of disease. Therefore, there is a demand for the development of novel therapies. Static magnetic stimulation (SMS) emerges as a new therapeutic option. The aim of this study was to evaluate the SMS effects on neuroblastoma cells in culture. MATERIALS AND METHODS: SH-SY5Y neuroblastoma cells were exposed to 0.3T SMS for 6, 12, 24, 36, 72 h, and 6 days. Cell viability (MTT), cell death (annexin-V/PI staining) and cell cycle (DNA content), cell proliferation (CFSE), autophagy (acridine orange), and total mitochondrial mass (MitoTracker™ Red) were analyzed to establish the cellular response to SMS. RESULTS: The viability of SH-SY5Y cells was reduced after exposure to SMS for 24 h and 6 days (p<0.05), without differences for the other times (p>0.05); however, this effect was not related to cell death or cell cycle arrest (p>0.05). In contrast, the viability of human malignant melanoma (HMV-II) cells, used as a tumoral control, was not affected. In addition, stimulated SH-SY5Y cells presented a decrease in mitochondrial mass at both exposure times and a reduction in autophagy and cell proliferation after 6 days (p<0.05). CONCLUSION: SMS application appears to be a promising adjuvant therapy for the treatment of neuroblastoma since it decreases the survival of SH-SY5Y neuroblastoma cells.

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.

Fibromialgia e disfunção temporomandibular: uma revisão de escopo / Fibromyalgia and temporomandibular disorder: a scoping review

A fibromialgia é uma síndrome complexa com alterações nociplásticas, caracterizadas por hiperalgesia e alodinia, frequentemente acompanhada pela presença de dor orofacial. Estudos têm demonstrado alta prevalência de disfunção temporomandibular (DTM) em pacientes fibromiálgicos, como fator etiológico ou agravante. O objetivo desta revisão de literatura foi identificar os mecanismos modulatórios comuns à fibromialgia e à DTM, e identificar diferentes modalidades de tratamento para os pacientes fibromiálgicos. Foram utilizados 69 artigos dos últimos 5 anos, além de 4 artigos conceituais anteriores a este período. Identificou-se que os principais fármacos utilizados para os sintomas de fibromialgia são pregabalina, amitriptilina, antidepressivos duais, tramadol, baixas doses de naltrexona e canabinoides. A associação de fármacos pode ser útil para aumentar a eficácia do tratamento e reduzir as doses dos mesmos. Por outro lado, novas terapias não farmacológicas, como as técnicas modulatórias não-invasivas, surgem como opções promissoras, promovendo alterações neuroplásticas importantes no tratamento. Conclusão: Há diversas opções terapêuticas farmacológicas e não-farmacológicas disponíveis no tratamento do paciente fibromiálgico para o especialista em DTM. Portanto, a combinação de diferentes abordagens pode auxiliar na obtenção de um protocolo individualizado, adequado às necessidades do paciente.

Fibromyalgia is a complex syndrome with nociplastic changes, characterized by hyperalgesia and allodynia, often accompanied by the presence of orofacial pain. Studies have shown a high prevalence of temporomandibular disorders (TMD) in fibromyalgia patients, as an etiological or aggravating factor. The aim of this review was to identify the modulatory mechanisms common to fibromyalgia and TMD, and to identify different treatment modalities for fibromyalgia patients. 69 articles from the last five years were included, in addition to 4 conceptual articles prior to this date. The main drugs used for fibromyalgia symptoms are pregabalin, amitriptyline, dual antidepressants, tramadol, low-dose naltrexone and cannabinoids. The combination of drugs may be useful in improving treatment efficacy and for reducing the drug's dose. On the other hand, new non-pharmacological therapies, such as non-invasive modulatory techniques, appear as promising options for treatment, promoting important neuroplastic alterations. Conclusion: Several pharmacological and non-pharmacological therapeutic alternatives are available for specialists in TMD. Therefore, combining therapy approaches can help create individualized protocols that are more effective at meeting the demands of fibromyalgia patients.

Functional connectivity response to acute pain assessed by fNIRS is associated with BDNF genotype in fibromyalgia: an exploratory study.

Fibromyalgia is a heterogenous primary pain syndrome whose severity has been associated with descending pain modulatory system (DPMS) function and functional connectivity (FC) between pain processing areas. The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism has been linked to vulnerability to chronic pain. In this cross-sectional imaging genetics study, we investigated fibromyalgia, the relationship between BDNF Val66Met heterozygous genotypes (Val/Met), and the functional connectivity (FC) response pattern to acute pain stimulus in the motor (MC) and prefrontal (PFC) cortex assessed by near-infrared spectroscopy (fNIRS) before and after a cold pressor test utilizing water (0-1 °C). Also, we assessed the relationship between this genotype with the DPMS function and quality of life. We included 42 women (Val/Val = 30; Val/Met = 12) with fibromyalgia, ages 18-65. The MANCOVA comparing Val/Met to Val/Val genotypes showed higher ΔFC between left(l)-PFC-l-MC (ß = 0.357, p = 0.048), l-PFC-right(r)-PFC (ß = 0.249, p = 0.012), l-PFC-r-MC (ß = 0.226, p = 0.022), and l-MC-r-PFC (ß = 0.260, p = 0.016). Val/Met genotypes showed higher efficiency of the DPMS and lower disability due to pain. Here we show that fibromyalgia patients carrying the Val/Met BDNF genotype presented an increased ΔFC across MC and PFC in response to acute pain associated with differences in acute pain perception and fibromyalgia symptoms.

Association between descending pain modulatory system and cognitive impairment in fibromyalgia: A cross-sectional exploratory study.

Background: The successful regulation of sensory input to the central nervous system depends on the descending pain modulatory system (DPMS). For the effective regulation of sensory input to the central nervous system and behavioral responses to pain, the DPMS is required. Its connection to fibromyalgia (FM)-related cognitive dysfunction has not yet been investigated. Therefore, this study tested whether measures of verbal fluency, sustained attention, and short-term and working memory could distinguish FM patients from healthy controls (HC). Additionally, it investigated, using a standardized paradigm, the link between cognitive ability and the function of the DPMS in responders and non-responders to the conditioned pain modulation test (CPM-test). Materials and methods: We enrolled 21 HC women and 69 FM patients, all of whom ranged in age from 30 to 65. We employed scores from the Trail Making Test (TMTB-A) (sustained and divided attention), the Controlled Oral Word Association Test (COWAT) (orthographic and semantic fluency), and the Digits subtest of the Wechsler Adult Intelligence Scale (WAIS-III) as dependent variables. Results: A generalized linear model (GLM) adjusted by educational level revealed significantly lower scores in FM than HC on the Span digits forward, COWAT-orthographic, and TMTB-A. For FM patients, multilevel MANCOVA revealed that the cognitive performance of non-responders compared to responders to CPM-test showed lower adjusted scores in Span digits forward (Partial-η2 = 0.358, P = 0.001), Span digits backward (Partial-η2 = 0.358, P = 0.001), COWAT-orthographic (Partial-η2 = 0.551, P = 0.001), COWAR-semantic (Partial-η2 = 0.355, P = 0.001), and TMTB-A (Partial-η2 = 0.360, P = 0.001). The association between the cognitive tests and the DPMS is moderated by the serum level of brain-derived neurotrophic factor (BDNF). Additionally, these cognitive assessments had a positive correlation with antidepressant use and pain threshold. The cognitive assessments, on the other hand, were conversely associated with a life of quality. Conclusion: Based on these findings, it can be shown that HC performed substantially better on cognitive exams than FM did. They demonstrated a link between clinical complaints about attention and memory and decreased DPMS effectiveness. Additionally, they demonstrated that the BDNF is a moderating element in a potential relationship between the severity of cognitive impairment and DPMS dysfunction.

Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction of the descending pain modulatory system in fibromyalgia.

INTRODUCTION: The association between descending pain modulatory system (DPMS) dysfunction and fibromyalgia has been previously described, but more studies are required on its relationship with aberrant functional connectivity (FC) between the motor and prefrontal cortices. OBJECTIVES: The objective of this cross-sectional observational study was to compare the intra- and interhemispheric FC between the bilateral motor and prefrontal cortices in women with fibromyalgia, comparing responders and nonresponders to the conditioned pain modulation (CPM) test. METHODS: A cross-sectional sample of 37 women (23 responders and 14 nonresponders to the CPM test) with fibromyalgia diagnosed according to the American College of Rheumatology criteria underwent a standardized clinical assessment and an FC analysis using functional near-infrared spectroscopy. DPMS function was inferred through responses to the CPM test, which were induced by hand immersion in cold water (0-1°C). A multivariate analysis of covariance for main effects between responders and nonresponders was conducted using the diagnosis of multiple psychiatric disorders and the use of opioid and nonopioid analgesics as covariates. In addition, we analyzed the interaction between the CPM test response and the presence of multiple psychiatric diagnoses. RESULTS: Nonresponders showed increased FC between the left motor cortex (lMC) and the left prefrontal cortex (lPFC) (t = -2.476, p = 0.01) and right prefrontal cortex (rPFC) (t = -2.363, p = 0.02), even when both were considered as covariates in the regression analysis (lMC-lPFC: ß = -0.127, t = -2.425, p = 0.021; lMC-rPFC: ß = -0.122, t = -2.222, p = 0.033). Regarding main effects, a significant difference was only observed for lMC-lPFC (p = 0.035). A significant interaction was observed between the psychiatric disorders and nonresponse to the CPM test in lMC-lPFC (ß = -0.222, t = -2.275, p = 0.03) and lMC-rPFC (ß = -0.211, t = -2.2, p = 0.035). Additionally, a significant interaction was observed between the CPM test and FC in these two region-of-interest combinations, despite the psychiatric diagnoses (lMC-lPFC: ß = -0.516, t = -2.447, p = 0.02; lMC-rPFC: ß = -0.582, t = -2.805, p = 0.008). CONCLUSIONS: Higher FC between the lMC and the bilateral PFC may be a neural marker of DPMS dysfunction in women with fibromyalgia, although its interplay with psychiatric diagnoses also seems to influence this association.

Spectral Power Density analysis of the resting-state as a marker of the central effects of opioid use in fibromyalgia.

Spectral power density (SPD) indexed by electroencephalogram (EEG) recordings has recently gained attention in elucidating neural mechanisms of chronic pain syndromes and medication use. We compared SPD variations between 15 fibromyalgia (FM) women in use of opioid in the last three months (73.33% used tramadol) with 32 non-users. EEG data were obtained with Eyes Open (EO) and Eyes Closed (EC) resting state. SPD peak amplitudes between EO-EC were smaller in opioid users in central theta, central beta, and parietal beta, and at parietal delta. However, these variations were positive for opioid users. Multivariate analyses of variance (ANOVAs) revealed that EO-EC variations in parietal delta were negatively correlated with the disability due to pain, and central and parietal beta activity variations were positively correlated with worse sleep quality. These clinical variables explained from 12.5 to 17.2% of SPD variance. In addition, central beta showed 67% sensitivity / 72% specificity and parietal beta showed 73% sensitivity/62% specificity in discriminating opioid users from non-users. These findings suggest oscillations in EEG might be a sensitive surrogate marker to screen FM opioid users and a promising tool to understand the effects of opioid use and how these effects relate to functional and sleep-related symptoms.

Transcranial direct current stimulation alters anxious-like behavior and neural parameters in rats with chronic pain exposed to alcohol.

The aim of this study was to evaluate the effects of transcranial direct current stimulation (tDCS) on anxiety-like behavior and neural parameters in rats with chronic pain exposed to alcohol. Thirty-six adult male Wistar rats were randomly assigned to control (CT), neuropathic pain (NP), NPtDCS, NP + alcohol (NPAL), or NPALtDCS groups, subjected to sciatic nerve chronic constriction injury (CCI) and exposed to alcohol (20% v/v solution, 4 g/kg) or vehicle by gavage for 15 days. Afterward, rats were treated using bimodal tDCS (0.5 mA/20 min/8 days) and tested in the open field. Rats were killed 24 h after the last behavioral assessment, and brain and spinal cord tissue samples were collected and processed for NPY immunohistochemistry, expression of Il1a and Il1b in the spinal cord, cerebellum, and hippocampus, and levels of IL-1α and IL-1ß in the same brain structures and the striatum. tDCS reverted the anxiety-like behavior induced by CCI and alcohol, and the increased expression of Il1a in the spinal cord induced by alcohol, which increased the expression of Il1b in the cerebellum. In addition, tDCS modulated the hypothalamic NPY-immunoreactivity, increased the levels of IL-1α in the hippocampus (like NP and AL), and increased the expression of Il1b in the spinal cord (like AL). Thus, this study shows that tDCS changes NP and alcohol-induced anxiety-like behavior, possibly through its central modulatory effect of NPY and spinal cord expression of Il1a and Il1b, being considered a treatment option for alcohol and NP-induced anxiety symptoms.

Exergame training-induced neuroplasticity and cognitive improvement in institutionalized older adults: A preliminary investigation.

BACKGROUND: Prior research has reported cognitive improvements in elderly individuals when mental and physical exercise are practiced simultaneously, as in exergaming. However, the molecular mechanisms driving this beneficial response remain unclear. Moreover, there is robust evidence that regular exercise increases neurotrophic factors and promotes neuroplasticity, contributing to cognitive improvement. This research aimed to assess the impact of a 6-week Xbox 360 Kinect exergame protocol on cognitive function and brain-derived neurotrophic factor (BDNF) levels in institutionalized older individuals. METHODS: Participants living in a long-term care facility were included. The intervention (Xbox 360 Kinect exergame protocol) was conducted individually and consisted of two sessions per week (40 min each) over 6 weeks. Participants' cognitive function (Montreal Cognitive Assessment, MoCA) was evaluated before and after the intervention. Blood samples (15 ml) were collected at the same time to measure BDNF levels. RESULTS: Although there were no changes in total MoCA scores, exergame training improved the "language" domain and demonstrated a tendency toward an improvement in the "abstraction" and "memory/delayed recall" domains. Furthermore, BDNF levels were significantly increased after the intervention. CONCLUSION: BDNF enhancement might mediate, at least in part, the cognitive changes induced by a 6-week Xbox 360 Kinect exergame protocol in institutionalized older adults.

Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss Without Altering Muscle Mass in Obese Rats Under Calorie Restriction: A Preliminary Investigation.

Obesity treatments, such as calorie restriction (CR), eventually lead to muscle wasting and higher rates of neuroinflammation, whereas hypothalamic inflammatory conditions impair body weight (BW) control. Nicotinamide riboside (NR) has been proposed against obesity but with little evidence on skeletal muscle tissue (SMT) and neuroinflammation. Therefore, we aimed to investigate the effects of CR on SMT and on hypothalamic inflammatory biomarkers in obese adult male Wistar rats, and whether NR supplementation alone or in combination with CR affects these parameters. Obesity was induced in rats through a cafeteria diet for 6 weeks. After that, a group of obese rats was exposed to CR, associated or not associated with NR supplementation (400 mg/kg), for another 4 weeks. As a result, obese rats, with or without CR, presented lower relative weight of SMT when compared with eutrophic rats. Rats under CR presented lower absolute SMT weight compared with obese and eutrophic rats, in addition to presenting elevated hypothalamic levels of TNF-α. NR supplementation, in all groups, enhanced weight loss and increased relative weight of the SMT. Furthermore, in animals under CR, NR reversed increases TNF-α levels in the hypothalamus. In this study, these data, although succinct, are the first to evidence the effects of NR on SMT and neuroinflammation when associated with CR, especially in obesity conditions. Therefore, this provides preliminary support for future studies in this investigative field. Furthermore, NR emerges as a potential adjuvant for preventing muscle mass loss in the weight loss processes.

The mapping of cortical activation by near-infrared spectroscopy might be a biomarker related to the severity of fibromyalgia symptoms.

The delta value of oxyhemoglobin (Δ-HbO) determined by functional near-infrared spectroscopy at prefrontal cortex (PFC) and motor cortex (MC) based on primary (25 °C) and secondary (5 °C) thermal stimuli presented a larger peak latency at left MC in fibromyalgia than in controls. The difference between HbO concentration 15 s after the thermal stimuli ending and HbO concentration before the thermal stimuli onset (Δ-HbO*) at left PFC increased 47.82% in fibromyalgia and 76.66% in controls. This value had satisfactory discriminatory properties to differentiate cortical activation in fibromyalgia versus controls. A receiver operator characteristics (ROC) analysis showed the Δ-HbO* cutoffs of - 0.175 at left PFC and - 0.205 at right PFC offer sensitivity and specificity of at least 80% in screening fibromyalgia from controls. In fibromyalgia, a ROC analysis showed that these cutoffs could discriminate those with higher disability due to pain and more severe central sensitization symptoms (CSS). The ROC with the best discriminatory profile was the CSS score with the Δ-HbO* at left PFC (area under the curve = 0.82, 95% confidence interval = 0.61-100). These results indicate that cortical activation based on Δ-HbO* at left PFC might be a sensitive marker to identify fibromyalgia subjects with more severe clinical symptoms.