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Fibromyalgia (FM) is a functional syndrome characterized by musculoskeletal, diffuse and persistent (> 3 months) chronic pain, that is also characterized by sleep disturbances, fatigue, humor changes and cognitive and psychological changes. Transcranial Pulsed Current Stimulation (tPCS) is a new Transcranial Electrical Stimulation (tES) that has been studied as a treatment option for chronic pain and neurological conditions . Studies have shown that tPCS is capable of pain and cognitive modulation; however, there are not enough studies with evidence of its efficacy.Therefore, the primary aim of this study is to evaluate the effects of tPCS in pain, evaluated through Visual Analogue Scale (VAS) in FM patients; besides that, it is aimed to evaluate the effects of tPCS on quality of life, cognitive impairments, pain pressure threshold, descending inhibitory system of pain, and serum levels of Brain Derived Neurotrophic Factor (BDNF) and S100 Calcium-Binding Protein B (S100B). A randomized, double-blinded, controlled with sham clinical trial will be conducted with 70 (Critical f: 2.003; ES: 0.76; alpha: 0.05; power: 0.80) women with Fibromyalgia, from 30 to 65 years with pain on the Visual Analogue Scale (VAS) higher than 6 in the last 3 months. All patients will read and sign an Informed Consent Form (ICF). Each patient will be randomized to either 1+4 sessions of tPCS (2mA, 6-10Hz, 1-20ms, 20-25 minutes) or Sham. Patients will complete the following questionnaires/tests: Visual Analogue Scale (VAS), Pittsburgh Sleep Quality Index (PSQI), Fibromyalgia Impact Questionnaire (FIQ), Pain Catastrophizing Scale (PCS), Profile of Chronic Pain (PCP), Conditioned Pain Modulation Task (CPM-T), Pain Pressure Threshold Task (PPT-T), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and blood collection for serum levels of BDNF and S100B. For the main outcome, comparison between variables during time will be made through linear regression, with an adjustment for baseline levels and possible confounders.

Resumo Objetivo O objetivo deste estudo foi avaliar o perfil nociceptivo e o uso de analgésicos em pacientes submetidos à cirurgia de reparo do manguito rotador. Além disso, os limiares nociceptivos e a integridade do sistema inibidor descendente, o catastrofismo da dor e a prevalência de dor nociceptiva ou neuropática também foram analisados. Métodos Este estudo foi aprovado pelo Comitê de Ética da Universidade La Salle (1.325.433/2015). Quarenta pacientes (maiores de 18 anos) submetidos à cirurgia de reparo do manguito rotador (divididos entre aqueles com lesões pequenas e grandes) participaram do estudo. Os instrumentos utilizados foram o Questionário Sociodemográfico, a Escala Funcional de Dor, a Escala Visual Análoga (EVA), o Teste Sensorial Quantitativo (QST) e a Tarefa de Modulação Condicionada da Dor (CPM). Resultados Os pacientes apresentaram diferenças significativas nos limiares de dor e QST de calor (teste t de amostras independentes) e qualidade do sono, humor e ansiedade (teste t pareado) nos grupos pré-operatórios. Houve uma correlação significativa entre CPM pré-operatória e EVA pós-operatória (correlação de Pearson). Observou-se que, no período pré-operatório, 38 pacientes utilizavam analgésico de forma contínua. Além disso, no período pós-operatório, o uso de opioides foi maior nos pacientes com lesões pequenas (13 pacientes) em comparação àqueles com lesões grandes (nove pacientes). Conclusão Os pacientes com lesão do manguito rotador não apresentaram alterações no sistema inibidor descendente, mas sim alterações nos limiares de dor, o que pode interferir no período pós-operatório e estar relacionado ao consumo de analgésicos.

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-08-02T15:56:40Z No. of bitstreams: 1 ilstorres.etal.pdf: 344129 bytes, checksum: 3c9bbbd6a5b28aeb04ad990951690d4a (MD5) Made available in DSpace on 2021-08-02T15:56:40Z (GMT). No. of bitstreams: 1 ilstorres.etal.pdf: 344129 bytes, checksum: 3c9bbbd6a5b28aeb04ad990951690d4a (MD5) Previous issue date: 2020 Objectives Caffeine is extensively consumed as a psychostimulant drug, acting on A1 and A2A adenosine receptors blockade. Chronic exposure to caffeine during gestation and breast-feeding may be involved in infant rat's behavioral and biochemical alterations. Our goal was to evaluate the effect of chronic caffeine exposure during gestation and breast-feeding in the functionality of adenosine A1 receptors in infant rats at P14. NTPDase and 5'-nucleotidase activities were also evaluated. Methods Mating of adult female Wistar rats was confirmed by presence of sperm in vaginal smears. Rats were divided into three groups on the first day of pregnancy: (1) control: tap water, (2) caffeine: 0.3 g/L until P14, and (3) washout caffeine: caffeine was changed to tap water at P7. Evaluation of nociceptive response was performed at P14 using hot plate (HP) and tail-flick latency (TFL) tests. A1 receptor involvement was assessed using caffeine agonist (CPA) and antagonist (DPCPX). Enzymatic activities assays were conducted in the spinal cord. Results Gestational and breastfeeding exposure to caffeine (caffeine and washout groups) did not induce significant alterations in thermal nociceptive thresholds (HP and TF tests). Both caffeine groups did not show analgesic response induced by CPA when compared to the control group at P14, indicating chronic exposure to caffeine in the aforementioned periods inhibits the antinociceptive effects of the systemic A1 receptor agonist administration. No effect was observed upon ectonucleotidase activities. Conclusions Our results demonstrate that chronic caffeine exposure in gestational and breastfeeding alters A1-mediated analgesic response in rats.

BACKGROUND This study assessed the effects of an acute stress model upon the long-term hyperalgesia induced by repeated morphine administration in neonatal rats. We also evaluated neurotrophins and cytokines levels; expressions of adenosine and acetylcholine receptors, and acetylcholinesterase enzyme at the spinal cord. MATERIAL AND METHODS Male Wistar rats were subjected to morphine or saline administration from P8 to P14. Thermal hyperalgesia and mechanical hyperesthesia were assessed using the hot plate (HP) and von Frey (vF) tests, respectively, at postnatal day P30 and P60. After baseline measurements, rats were subjected to a single exercise session, as an acute stress model, at P30 or P60. We measured the levels of BDNF and NGF, interleukin-6, and IL-10 in the cerebral cortex and the brainstem; and the expression levels of adenosine and muscarinic receptors, as well as acetylcholinesterase (AChE) enzyme at the spinal cord. RESULTS A stress exercise session was not able to revert the morphine-induced hyperalgesia. The morphine and exercise association in rats induced a decrease in the neurotrophins brainstem levels, and A1 , A2A , A2B receptors expression in the spinal cord, and an increase in the IL-6 cortical levels. The exercise reduced M2 receptors expression in the spinal cord of naive rats, while morphine prevented this effect. CONCLUSIONS Single session of exercise does not revert hyperalgesia induced by morphine in rats; however, morphine plus exercise modulate neurotrophins, IL-6 central levels, and expression of adenosine receptors.

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-08-02T19:11:58Z No. of bitstreams: 1 bclopes.etal2.pdf: 928490 bytes, checksum: bf669722d86cf476c34fed69f52984f4 (MD5) Made available in DSpace on 2021-08-02T19:11:58Z (GMT). No. of bitstreams: 1 bclopes.etal2.pdf: 928490 bytes, checksum: bf669722d86cf476c34fed69f52984f4 (MD5) Previous issue date: 2020 Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-08-02T19:12:18Z No. of bitstreams: 1 bclopes.etal2.pdf: 928490 bytes, checksum: bf669722d86cf476c34fed69f52984f4 (MD5) Made available in DSpace on 2021-08-02T19:12:18Z (GMT). No. of bitstreams: 1 bclopes.etal2.pdf: 928490 bytes, checksum: bf669722d86cf476c34fed69f52984f4 (MD5) Previous issue date: 2020 Background Behavioral alterations, like mechanical and thermal hyperalgesia, and modulation of biomarkers in the peripheral and central nervous systems (CNS) are markers of chronic pain. Transcranial direct current stimulation (tDCS) with exercise is a promising therapy for pain due to its neuromodulatory capacity. Objective To assess the individual effects of tDCS, exercise, and the two combined on the nociceptive response and BDNF, IL-1β, and IL-4 levels in the CNS structures of rats in a chronic pain model. Methods For 8 consecutive days after the establishment of chronic neuropathic pain by inducing a constriction injury to the sciatic nerve (CCI), the rats received tDCS, exercise, or both treatments combined (20 min/day). The hyperalgesic response was assessed by von Frey and hot plate tests at baseline, 7, and 14 days after CCI surgery and immediately, 24 h, and 7 days after the end of treatment. The BDNF, IL-1β, and IL-4 levels were assessed in the cerebral cortex, brainstem, and spinal cord by enzyme-linked immunosorbent assay at 48 h and 7 days after the end of treatment. Results The CCI model triggered marked mechanical and thermal hyperalgesia. However, bimodal tDCS, aerobic exercise, and the two combined relieved nociceptive behavior for up to 7 days following treatment completion. Conclusions Bimodal tDCS, aerobic exercise, or both treatments combined promoted analgesic effects for neuropathic pain. Such effects were reflected by cytokine modulation throughout the spinal cord-brainstem-cerebral cortex axis.

Anxiety is one of the most prevalent and debilitating psychiatric conditions worldwide. Pharmaco- and psycho-therapies have been employed in the treatment of human anxiety to date. Yet, either alone or in combination, unsatisfactory patient outcomes are prevalent, resulting in a considerable number of people whose symptoms fail to respond to conventional therapies with symptoms remaining after intervention. The demand for new therapies has given birth to several noninvasive brain stimulation techniques. Transcranial direct current stimulation (tDCS) has arisen as a promising tool and has been proven to be safe and well tolerated for the treatment of many diseases, including chronic pain, depression, and anxiety. Here, reports of the use of tDCS in anxiety disorders in human patients were reviewed and summarized. A literature search was conducted in mid-2019, to identify clinical studies that evaluated the use of tDCS for the treatment of anxiety behavior. The PubMed, Web of Science, and Scielo and PsycInfo databases were explored using the following descriptors: "anxiety", "anxious behavior", "tDCS", and "transcranial direct current stimulation". Among the selected articles, considerable variability in the type of tDCS treatment applied in interventions was observed. Evidence shows that tDCS may be more effective when used in combination with drugs and cognitive behavioral therapies; however future large-scale clinical trials are recommended to better clarify the real effects of this intervention alone, or in combination with others.

Fibromyalgia (FM) is a chronic pain syndrome that affects the central nervous system and generates disability, which is characterized by generalized pain, fatigue, and functional decline. In this review, we aimed to identify the polymorphisms related to the pathophysiology of FM and the clinical characteristics generated by genetic influence. Only original studies with genes related to FM were considered, totaling 27 articles. The genes found were: MTHFR, RGS4, MYT1L, TACR1, SCN9A, DRD3, ADRB2, IL-4, HLA-DRB1, EDN1, CNR1, TAAR1, OPRM1, ADRA1A, ADRB3, BDNF, GRIA4, HTR3A, HTR3B, HTR2A, SERPINA 1 or A1AT, NRXN3, GCH1, MEFV, TRPV3, SLC6A4, ACE I/D, TSPO, COMT, and MAOA. Several genes related to different pain syndromes and altered pain thresholds have been identified and some polymorphisms were related to susceptibility to FM. It was observed that 73.33% of the genes related to FM were also associated with some psychological disorders, such as anxiety, depression, schizophrenia, and obsessive and compulsive disorder, and 40.00% with pain sensitivity and/or migraine, besides other disorders associated (drug addiction, autoimmune disorders, circulatory problems, and metabolic alterations). This review demonstrated an association of FM and genetic polymorphisms that can expand our knowledge about the pathophysiology of this disease.

This study aimed to evaluate the effects of repeated bimodal transcranial direct current stimulation (tDCS) on alcohol consumption and immunohistological and neurochemical parameters in nerve-injured rats. Forty-eight adult male Wistar rats were distributed into six groups: control, neuropathic pain (NP) + sham-tDCS, NP + alcohol + sham-tDCS, alcohol + sham-tDCS, alcohol + tDCS, and NP + alcohol + tDCS. NP is induced by chronic sciatic nerve constriction (CCI). The rats were exposed to a 10% alcohol solution by voluntary consumption for 14 days. From the 16th day after surgery, bimodal tDCS was applied for 20 min/day for 8 days. Brain structures were collected to evaluate the number of neuropeptide Y (NPY)-positive neurons, neurites, and argyrophilic grains by immunohistochemistry, and brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), interleukin (IL)-6, and IL-10 by ELISA. Nerve-injured rats showed a progressive increase in alcohol consumption compared to the non-injured rats. In addition, there was a reduction in voluntary alcohol consumption over time induced by tDCS. Alcohol exposure, chronic pain, and tDCS treatment modulated the central NPY immunoreactivity. tDCS increased the cerebellar levels of IL-6 and IL-10, and CCI and/or tDCS reduced striatal BDNF levels. The current data suggest that tDCS could be a promising non-pharmacological adjuvant to treat patients with chronic pain who use alcohol to relieve their symptoms.

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-08-02T15:06:28Z No. of bitstreams: 1 glaste.etal.pdf: 178409 bytes, checksum: c9711e0d6e5fcf157ff37a7cb122c737 (MD5) Made available in DSpace on 2021-08-02T15:06:28Z (GMT). No. of bitstreams: 1 glaste.etal.pdf: 178409 bytes, checksum: c9711e0d6e5fcf157ff37a7cb122c737 (MD5) Previous issue date: 2021 BACKGROUND AND OBJECTIVES: To pursue safer and more effective treatments for rheumatoid arthritis, the effect of dexamethasone treatment (DEX, 0.25mg/kg) combined with transcranial direct current stimulation (tDCS) in the behavior and neurochemical parameters of arthritic rats was evaluated. METHODS: Thirty-six Wistar rats were divided into four groups: control+DEX (CTRL+DEX), arthritis+DEX (RA+DEX), arthritis+DEX+sham-tDCS (RA+DEX+sham-tDCS) and arthritis+DEX+tDCS (RA+DEX+tDCS). The arthritic model (RA) was induced by complete Freund’s adjuvant (CFA) paw administration. Paw edema and mechanical allodynia were assessed by plethysmometer and von Frey apparatus, respectively. Fourteen days after the CFA injection, rats received the treatment for eight days (DEX and/or tDCS). Behavioral parameters were measured with the Open-Field test. ELISA was used to evaluate hippocampal and spinal cord tumor necrosis factor (TNF-α) levels, cerebral cortex and brainstem BDNF levels. RESULTS: In pre-treatment measurements, arthritic rats presented an increase in joint swelling and mechanical allodynia when compared to the control group, confirming chronic pain establishment. A slight antinociceptive effect of dexamethasone combined with tDCS in the pain model was observed. The pain model significantly induced an increase in the grooming behavior and a reduction in the spinal cord and hippocampal TNF-α levels; these effects were reverted in the sham- and active-tDCS-treated rats. However, no effects of DEX or tDCS were observed in the BDNF levels in the cerebral cortex and brainstem. CONCLUSION: Despite the small effect observed, tDCS treatment cannot be discarded as a non-pharmacological adjuvant technique for inflammatory chronic pain treatment.

BACKGROUND AND OBJECTIVES: The expression of nerve growth factor (NGF) in the large-size neurons may represent a key role in the neuronal synaptic plasticity and re-organization of neuronal function after a nerve injury. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising tool to pain management since it promotes neuroplasticity in the central system, and it can be combined with other interventions. The aim was to investigate the effects of tDCS in the NGF levels in central and peripheral nervous system structures of rats submitted to a neuropathic pain (NP) model. METHODS: The chronic constriction injury (CCI) of sciatic nerve was used for the induction of NP. For sham surgery, the sciatic nerve was exposed, but without any ligation. The control group did not undergo surgical procedure. After the establishment of NP, treated groups were subjected to tDCS treatment 0.5 mA/20min/day/8 days. NGF levels in cerebral cortex, spinal cord and sciatic nerve were determined by sandwich-ELISA at 48 hours and 7 days after the end of treatment. RESULTS: The CCI model increased NGF levels in all three structures analyzed at long-lasting time, evidencing the importance of this neurotrophin in neuropathic pain condition. On the other hand, there was no tDCS effect in the central and peripheral NGF levels discarding the participation of this neurotrophin in the analgesic tDCS effect. CONCLUSION: tDCS modulation effects of nociceptive pathways seem not to be linked to the NGF signaling in this chronic pain model. RESUMO JUSTIFICATIVA E OBJETIVOS: A expressão do fator de crescimento neural (NGF) em neurônios de diâmetro largo pode representar um papel importante na plasticidade sináptica neuronal e na reorganização da função neuronal após lesão neural. A estimulação transcraniana por corrente contínua (ETCC) é um método não invasivo de estimulação cerebral e representa uma ferramenta promissora para o manejo da dor, pois promove neuroplasticidade no sistema central, podendo ser combinada com outras intervenções. O objetivo foi investigar os efeitos da ETCC nos níveis de NGF em estruturas do sistema nervoso central e periférico de ratos submetidos a um modelo de dor neuropática (DN). MÉTODOS: A constrição crônica (CCI) do nervo isquiático foi utilizada para indução do modelo de DN. Na cirurgia sham, o nervo foi exposto, no entanto não houve constrição do nervo. O grupo controle não foi submetido ao procedimento cirúrgico. Após estabelecimento da DN, os grupos tratados foram submetidos a ETCC 0,5 mA/20min/dia/8 dias. Os níveis de NGF no córtex cerebral, medula espinal e nervo isquiático foram mensurados pela técnica de ELISA 48 horas e 7 dias após o final do tratamento. RESULTADOS: O modelo de dor CCI aumentou os níveis de NGF nas três estruturas analisadas, evidenciando a importância desta neurotrofina na dor neuropática. Por outro lado, não houve efeito da ETCC nos níveis de NGF central e periférico, descartando o papel desta neurotrofina no efeito analgésico da ETCC. CONCLUSÃO: Efeitos da ETCC sobre vias nociceptivas não estão diretamente relacionados com a sinalização do NGF neste modelo de dor crônica.

Background/aim Magnetic stimulation is used in the treatment of a diversity of diseases, but a complete understanding of the underlying mechanisms of action requires further investigation. We examined the effect of static magnetic stimulation (SMS) in different cell lines. Materials and methods A culture plate holder with attached NeFeB magnets was developed. Different magnetic field intensities and periods were tested in tumoral and non-tumoral cell lines. To verify the cellular responses to SMS, cell viability, cell death, cell cycle and BDNF expression were evaluated. Results Exposure of SH-SY5Y cells to SMS for 24 hours led to a decrease in cell viability. Analysis 24 h after stimulation revealed a decrease in apoptotic and double-positive cells, associated with an increase in the number of necrotic cells. Conclusion The effects of SMS on cell viability are cell type-specific, inducing a decrease in cell viability in SH-SY5Y cells. This suggests that SMS may be a potential tool in the treatment of neuronal tumors.

Trigeminal neuralgia (TN) is a type of neuropathic pain characterized by intense pain; although anticonvulsants are used as an option to relieve pain, adverse side effects can decrease patient adherence. In this context, a low dose of naltrexone is effective in relieving pain in other pain conditions. Thus, the objective of the present study was to evaluate the analgesic effect of low-dose naltrexone on facial mechanical allodynia in a rat model of TN, as well as its effect(s) on biomarkers in the central nervous system (tumor necrosis factor-alpha, brain-derived neurotrophic factor [BDNF], interleukin [IL]-10, and toll-like receptor-4). Fifty-nine adult male Wistar rats (CEUA-HCPA#2017-0575) were allocated to following groups: control; sham-pain + vehicle; sham-pain + carbamazepine (100 mg/kg); sham-pain + naltrexone (0.5 mg/kg); pain + vehicle; pain + carbamazepine; and pain + naltrexone. TN was induced using chronic constriction of the infraorbital nerve. Facial allodynia was assessed using von Frey test. Drugs were administered by gavage 14 days after surgery for 10 days. At baseline, the mechanical threshold was similar between groups (P 0.05; generalized estimating equation). Seven days after surgery, facial allodynia was observed in sham-TN and pain-TN groups (P 0.05). Fourteen days after surgery, only pain-TN groups exhibited facial allodynia. The first dose of low-dose naltrexone or carbamazepine partially reversed facial allodynia. After 10 days of treatment, both drugs completely reversed it. Spinal cord levels of BDNF and IL-10 were modulated by low-dose naltrexone. Thus, low-dose naltrexone may be suitable to relieve TN; however, the exact mechanisms need to be clarified.

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-08-02T19:22:20Z No. of bitstreams: 1 dssantos.etal.pdf: 1011031 bytes, checksum: 842db784f2614332709acda76d12496c (MD5) Made available in DSpace on 2021-08-02T19:22:20Z (GMT). No. of bitstreams: 1 dssantos.etal.pdf: 1011031 bytes, checksum: 842db784f2614332709acda76d12496c (MD5) Previous issue date: 2020 Neuromodulatory techniques have been studied to treat drug addiction or compulsive eating as well as different chronic pain conditions, such as neuropathic and inflammatory pain in the clinical and preclinical settings. In this study, we aimed to investigate the effect of transcranial direct current stimulation (tDCS) on the association of alcohol withdrawal with neuropathic pain based on nociceptive and neurochemical parameters in rats. Thirty-six adult male Wistar rats were randomized into five groups: control, neuropathic pain, neuropathic pain + tDCS, neuropathic pain + alcohol, and neuropathic pain + alcohol + tDCS. The neuropathic pain model was induced by chronic constriction injury (CCI) to the sciatic nerve. Rats were then exposed to alcohol (20%) by oral gavage administration for 15 days (beginning 24 h after CCI). tDCS was started on the 17th day after surgery and lasted for 8 consecutive days. The nociceptive test (hot plate) was performed at baseline, 16 days after CCI, and immediately and 24 h after the last session of tDCS. Rats were killed by decapitation, and structures were removed and frozen for biochemical analysis (nerve growth factor and interleukin (IL-1α, IL-1β, and IL-10 measurements). Neuropathy-induced thermal hyperalgesia was reversed by tDCS, an effect that was delayed by alcohol abstinence. In addition, tDCS treatment induced modulation of central levels of IL-1α, IL-1ß, and IL-10 and neurotrophic growth factor. We cannot rule out that the antinociceptive effect of tDCS could be related to increased central levels of IL-1α and IL-10. Therefore, tDCS may be a promising non-pharmacological therapeutic approach for chronic pain treatment.

BACKGROUND Transcranial direct-current stimulation (tDCS) is a noninvasive method of brain stimulation suggested as a therapeutic tool for pain and is related to the reversal of maladaptive plasticity associated with chronic pain. OBJECTIVES This study investigated the effect of tDCS, a non-pharmacological therapy, on local mechanical hyperalgesia, and remote thermal hyperalgesia in rats submitted to orofacial inflammatory pain model, by facial von Frey and hot plate tests, respectively. In addition, we evaluated levels of BDNF, NGF, IL-10 and IL-6 in the brainstem and blood serum of these animals at 24 hours and 7 days after the end of tDCS treatment. METHODS Rats were subjected to temporomandibular joint pain and treated with tDCS. The animals were divided into control, pain and pain + treatment groups. Mechanical and thermal hyperalgesia were evaluated at baseline, 7 days after administration of complete Freund's adjuvant, and immediately, 24 hours, and 7 days after the tDCS treatment. Neuroimmunomodulators levels were determined by ELISA. Statistical analyses were performed by (GEE)/Bonferroni (behavioural tests), three-way ANOVA/SNK (neurochemical tests) and Kruskal-Wallis (histological analysis). RESULTS Transcranial direct-current stimulation reduced mechanical and thermal hyperalgesia (P

The present study aimed to determine whether isoflurane interferes with the analgesic effects of acupuncture (Ac) and electroacupuncture (EA), using a neuropathic pain (NP) rat model. In total, 140 male Wistar rats were used; isoflurane-induced nociceptive response was evaluated using the von Frey test, serum calcium-binding protein β (S100β) levels and nerve growth factor (NGF) levels in the left sciatic nerve. The NP model was induced by chronic constriction injury of the sciatic nerve at 14 days after surgery. Treatment was initiated after NP induction with or without isoflurane anesthesia (20 min/day/8 days). The von Frey test was performed at baseline, 14 days postoperatively, and immediately, 24 h, and 48 h after the last treatment. Results of the nociceptive test and three-way analysis of variance were analyzed by generalized estimating equations, the Bonferroni test, followed by Student–Newman–Keuls or Fisher's least significant difference tests for comparing biochemical parameters (significance defined as p ≤ 0.05). At baseline, no difference was noted in the nociceptive response threshold among all groups. Fourteen days after surgery, compared with other groups, NP groups showed a decreased pain threshold, confirming establishment of NP. Ac and EA enhanced the mechanical pain threshold immediately after the last session in the NP groups, without anesthesia. Isoflurane administration caused increased nociceptive threshold in all groups, and this effect persisted for 48 h after the last treatment. There was an interaction between the independent variables: pain, treatments, and anesthesia in serum S100β levels and NGF levels in the left sciatic nerve. Isoflurane enhanced the analgesic effects of Ac and EA and altered serum S100β and left sciatic nerve NGF levels in rats with NP. Keywords: acupuncture, electroacupuncture, isoflurane, neuropathic pain

This study aimed to answer these questions: (i) Can the temporal patterns of locomotor and exploratory activities and anxiety-like behavior be disrupted by a single session of stress? (ii) Can the ...

Anxiety disorders cause distress and are commonly found to be comorbid with chronic pain. Both are difficult-to-treat conditions for which alternative treatment options are being pursued. This study aimed to evaluate the effects of transcranial direct current stimulation (tDCS), treadmill exercise, or both, on anxiety-like behavior and associated growth factors and inflammatory markers in the hippocampus and sciatic nerve of rats with neuropathic pain. Male Wistar rats (n = 216) were subjected to sham-surgery or sciatic nerve constriction for pain induction. Fourteen days following neuropathic pain establishment, either bimodal tDCS, treadmill exercise, or a combination of both was used for 20 min a day for 8 consecutive days. The elevated plus-maze test was used to assess anxiety-like behavior and locomotor activity during the early (24 h) or late (7 days) phase after the end of treatment. BDNF, TNF-ɑ, and IL-10 levels in the hippocampus, and BDNF, NGF, and IL-10 levels in the sciatic nerve were assessed 48 h or 7 days after the end of treatment. Rats from the pain groups developed an anxiety-like state. Both tDCS and treadmill exercise provided ethological and neurochemical alterations induced by pain in the early and/or late phase, and a modest synergic effect between tDCS and exercise was observed. These results indicate that non-invasive neuromodulatory approaches can attenuate both anxiety-like status and locomotor activity and alter the biochemical profile in the hippocampus and sciatic nerve of rats with neuropathic pain and that combined interventions may be considered as a treatment option.

Melatonin is a neuroendocrine hormone that presents a wide range of physiological functions including regulating circadian rhythms and sleep, enhancing immune function, sleep improvement, and antioxidant effects. In addition, melatonin has received special attention in pain treatment since it is effective and presents few adverse effects. In this study, we evaluated the effect of acute dose of melatonin upon hyperalgesia induced by complete Freund's adjuvant in a chronic orofacial pain model in Sprague-Dawley rats. Nociceptive behavior was assessed by facial Von Frey and the hot plate tests at baseline and thereafter 30, 60, and 120 min, 24 h, and 7 days after melatonin treatment. We demonstrated that acute melatonin administration alters mechanical and thermal hyperalgesia induced by an orofacial pain model (TMD), highlighting that the melatonin effect upon mechanical hyperalgesia remained until 7 days after its administration. Besides, we observed specific tissue profiles of neuroimmunomodulators linked to pain conditions and/or melatonin effect (brain-derived neurotrophic factor, nerve growth factor, and interleukins 6 and 10) in the brainstem levels, and its effects were state-dependent of the baseline of these animals.

Background Neuropathic pain (NP) is caused by an insult or dysfunction in the peripheral or central nervous system (CNS), the main symptoms being mechanical allodynia and hyperalgesia. NP often shows insufficient response to classic analgesics and its management remains a challenge. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising resource for pain management. Objective/hypothesis We investigated the effects of tDCS on the nociceptive response and on IL-1β, IL-10, and TNF-α levels in CNS structures of rats with NP. Methods After induction of NP by chronic constriction injury (CCI) of the sciatic nerve, the rats received 20 min of bicephalic tDCS for 8 days. Hyperalgesia was assessed by the hot plate and von Frey tests and evaluated at baseline, 7 days, and 14 days after CCI surgery, and also immediately, 24 hours, and 7 days following tDCS treatment. The levels of IL-1β, IL-10 and TNF-α in the cortex, spinal cord, and brainstem were determined by ELISA at 48 hours and 7 days post-tDCS. Results The CCI model provoked thermal and mechanical hyperalgesia until at least 30 days post-CCI; however, bicephalic tDCS relieved the nociceptive behavior for up to 7 days after treatment completion. Conclusions Bicephalic tDCS is effective to promote antinociceptive behavior in neuropathic pain, which can be reflected by a spinal neuroimmunomodulation linked to pro- and anti-inflammatory cytokine levels observed in the long-term.

Attention deficit hyperactivity disorder (ADHD) is characterized by impairing levels of hyperactivity, impulsivity and inattention. However, different meta-analyses have reported disruptions in short and long-term memory in ADHD patients. Previous studies indicate that mnemonic dysfunctions might be the result of deficits in attentional circuits, probably due to ineffective dopaminergic modulation of hippocampal synaptic plasticity. In this study we aimed to evaluate the potential therapeutic effects of a neuromodulatory technique, transcranial direct current stimulation (tDCS), in short-term memory (STM) deficits presented by the spontaneous hypertensive rats (SHR), the most widely used animal model of ADHD. Adult male SHR and Wistar Kyoto rats (WKY) were subjected to a constant electrical current of 0.5 mA intensity applied on the frontal cortex for 20 min/day during 8 days. STM was evaluated with an object recognition test conducted in an open field. Exploration time and locomotion were recorded, and brain regions were dissected to determine dopamine and BDNF levels. SHR spent less time exploring the new object when compared to WKY, and tDCS improved object recognition deficits in SHR without affecting WKY performance. Locomotor activity was higher in SHR and it was not affected by tDCS. After stimulation, dopamine levels were increased in the hippocampus and striatum of both strains, while BDNF levels were increased only in the striatum of WKY. These findings suggest that tDCS on the frontal cortex might be able to improve STM deficits present in SHR, which is potentially related to dopaminergic neurotransmission in the hippocampus and striatum of those animals.

Epidemiological studies show that painful disorders are more prevalent in women than in men, and the transcranial direct current stimulation (tDCS) technique has been tested in chronic pain states. We explored the effect of tDCS on pain behavior and brain-derived neurotrophic factor (BDNF) levels in ovariectomized rats.Forty-five female Wistar adult rats were distributed into five groups: control (CT), ovariectomy + tDCS (OT), ovariectomy + sham tDCS (OS), sham ovariectomy + tDCS (ST), and sham ovariectomy+shamtDCS (SS). The rats were subjected to cathodal tDCS. The vaginal cytology and the estradiol levels confirmed the hormonal status. In addition, nociceptive behavior was evaluated using the tail-flick, von Frey, and hot-plate tests, as well as the BDNF levels in the serum, hypothalamus, hippocampus, spinal cord, and cerebral cortex. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical analysis, followed by the Bonferroni, and P-value b 0.05 was considered significant.The ovariectomized animals presented a hypersensitivity response in the hot-plate (P b 0.01) and von Frey (P b 0.05) tests, as well as increased serum BDNF (P b 0.05) and decreased hypothalamic BDNF (P b 0.01) levels. The OT, OS, ST, and SS groups showed decreased hippocampal BDNF levels as compared with the control group (P b 0.001). The interaction between tDCS and ovariectomy on the cortical BDNF levels (P b 0.01) was observed.The ovariectomy induced nociceptive hypersensitivity and altered serum and hypothalamic BDNF levels. The cathodal tDCS partially reversed nociceptive hypersensitivity.

Objective Our objective was to evaluate the Transcranial direct current stimulation (tDCS) effect on facial allodynia induced by chronic constriction of the infraorbital nerve (CCI-ION) and on the brainstem levels of TNF-α, NGF, IL-10, and serum LDH in rats. Methods Rats were exposed to the CCI-ION model. Facial allodynia was assessed by von Frey filaments test at baseline, 3, 7, 10, and 14 days postsurgery and 24 hr and 7 days after the bimodal tDCS sessions for 20 min/day/8 days. Results Chronic constriction of the infraorbital nerve induced a significant decrease in the mechanical threshold 14 days after surgery. This effect was reversed by tDCS treatment, with the mechanical threshold returning to basal levels at 24 hr after the end of the treatment and it persisted for 7 days after the end of the treatment. tDCS also decreased LDH serum levels compared to those in the control group. There was an interaction between pain and treatment with respect to brainstem levels of NGF, TNF-α, and IL-10. Conclusion Chronic constriction of the infraorbital nerve model was effective in establishing trigeminal neuropathic pain on 14 days after surgery, and tDCS reduced allodynia and LDH serum levels and promoted alterations in NGF, TNF-α, and IL-10 brainstem levels. Thus, we suggest that tDCS may be a potential therapy in the trigeminal pain treatment.

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-08-03T14:45:27Z No. of bitstreams: 1 asouza.etal.pdf: 1041409 bytes, checksum: 7c3564560a848231e34c4d8068854532 (MD5) Made available in DSpace on 2021-08-03T14:45:27Z (GMT). No. of bitstreams: 1 asouza.etal.pdf: 1041409 bytes, checksum: 7c3564560a848231e34c4d8068854532 (MD5) Previous issue date: 2018 Background: Neuropathic pain is relatively common and occurs in approximately 6–8% of the population. It is associated with allodynia and hyperalgesia. Thus, non-pharmacological treatments, such as transcranial direct current stimulation (tDCS) may be useful for relieving pain. Objectives: This study aimed to investigate the antiallodynic effect of tDCS in a mice model of neuropathic pain, and the underlying neurotransmission systems that could drive these effects. Methods: Male, Swiss mice, weighing 25–35 g, were subjected to partial sciatic nerve ligation (PSNL). Allodynia was assessed using a Von Frey filament (0.6 g). First, the behavioral time-course of these mice was assessed after 5, 10, 15 and 20 min of tDCS (0.5 mA). Second, the mice that underwent PSNL were assigned to either the tDCS (0.5 mA, 15 min) or tDCS sham group, and further assigned to receive either saline or a drug (i.e., naloxone, yohimbine, a-methyl-p-tyrosine, q-chlorophenylalanine methyl ester, caffeine, 1,3-dipropyl-8-cyclopentylxanthine, AM281, AM630, flumazenil, MK-801, or lidocaine). Results: The antiallodynic effect of tDCS lasted 2 h and 4 h, after 10 min and 15 or 20 min of treatment, respectively (P < .001, P < .01, and P < .05, respectively). The antiallodynic effect of tDCS was associated with all the systems that were analyzed, i.e., the opioidergic (P < .01), adenosinergic (P < .001), serotonergic (P < .01), noradrenergic (P < .001), cannabinoid (P < .001), GABAergic, and glutamatergic (P < .001) systems. Lidocaine did not reverse the antiallodynic effect of tDCS (P > .05). Conclusion: The antiallodynic effect of tDCS was associated with different neurotransmitters systems; the duration of these after-effects depended on the time exposure to tDCS.

The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3 g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development.

Chronic myofascial pain syndrome has been related to defective descending inhibitory systems. Twenty-four females aged 19 to 65 years with chronic myofascial pain syndrome were randomized to receive 10 sessions of repetitive transcranial magnetic stimulation (rTMS) (n = 12) at 10 Hz or a sham intervention (n = 12). We tested if pain (quantitative sensory testing), descending inhibitory systems (conditioned pain modulation [quantitative sensory testing + conditioned pain modulation]), cortical excitability (TMS parameters), and the brain-derived neurotrophic factor (BDNF) would be modified. There was a significant interaction (time vs group) regarding the main outcomes of the pain scores as indexed by the visual analog scale on pain (analysis of variance, P.01). Post hoc analysis showed that compared with placebo-sham, the treatment reduced daily pain scores by -30.21% (95% confidence interval = -39.23 to -21.20) and analgesic use by -44.56 (-57.46 to -31.67). Compared to sham, rTMS enhanced the corticospinal inhibitory system (41.74% reduction in quantitative sensory testing + conditioned pain modulation, P.05), reduced the intracortical facilitation in 23.94% (P = .03), increased the motor evoked potential in 52.02% (P = .02), and presented 12.38 ng/mL higher serum BDNF (95% confidence interval = 2.32-22.38). No adverse events were observed. rTMS analgesic effects in chronic myofascial pain syndrome were mediated by top-down regulation mechanisms, enhancing the corticospinal inhibitory system possibly via BDNF secretion modulation.High-frequency rTMS analgesic effects were mediated by top-down regulation mechanisms enhancing the corticospinal inhibitory, and this effect involved an increase in BDNF secretion.

Aims: The objective was to evaluate the single exposure of general a nesthetics with or without a surgical procedure at postnatal day 14 (P14) on nociceptive behavioral responses. Furthermore, we evaluated ectonucleotidase activities at P14 and P30. Place of Study:All experiments were performed at the Animal Experimentatio n Unit of Hospital de ClInicas de Porto Alegre. The Institutional Committee approved the OriginalResearch Article

Pain catastrophizing regularly occurs in chronic pain patients. It has been suggested that pain catastrophizing is a stable, person-based construct. These findings highlight the importance of investigating catastrophizing in conceptualizing specific approaches for pain management. One important area of investigation is the mechanism underlying pain catastrophizing. Therefore, this study explored the relationship between a neurophysiological marker of cortical excitability, as assessed by transcranial magnetic stimulation, and catastrophizing, as assessed by the Brazilian Portuguese Pain Catastrophizing Scale, in patients with chronic myofascial pain syndrome. The Pain Catastrophizing Scale is a robust questionnaire used to examine rumination, magnification and helplessness that are associated with the experience of pain. We include 24 women with myofascial pain syndrome. The Brazilian Portuguese Pain Catastrophizing Scale and cortical excitability were assessed. Functional and behavioral aspects of pain were evaluated with a version of the Profile of Chronic Pain scale and by multiple pain measurements (eg, pain intensity, pressure pain threshold, and other quantitative sensory measurements). Intracortical facilitation was found to be significantly associated with pain catastrophizing (β = .63, P = .001). Our results did not suggest that these findings were influenced by other factors, such as age or medication use. Furthermore, short intracortical inhibition showed a significant association with pressure pain threshold (β = .44, P = .04). This study elaborates on previous findings indicating a relationship between cortical excitability and catastrophizing. The present findings suggest that glutamatergic activity may be associated with mechanisms underlying pain catastrophizing; thus, the results highlight the need to further investigate the neurophysiological mechanisms associated with pain and catastrophizing. Perspective This study highlights the relationship between cortical excitability and catastrophizing. Cortical measures may illuminate how catastrophizing responses may be related to neurophysiological mechanisms associated with chronic pain.

To analyze the anti-inflammatory and analgesic effects of an adhesive resin containing indomethacin-loaded nanocapsules in rat model.Adhesive resin disks with or without indomethacin-loaded nanocapsules were subcutaneously implanted into right hind paw of rats. A week after surgical procedure, 2% formalin solution was intradermally injected into plantar surface of paw. Nociceptive and inflammatory responses were evaluated by formalin test. Paw edema by pletismometer and mechanical hyperalgesia by von Frey test were performed on day 2, day 4, day 6, day 8, day 10 and day 12 after surgery. IL-6, IL-10, and lactate dehydrogenase (LDH) serum levels were determined by ELISA-sandwich test.Group containing indomethacin-loaded nanocapsules (NC) presented lower edema in the right hind paw at 24h after formalin injection than those of the control group (CT) (P0.01). NC group showed decrease in the nociceptive response in phase I (neurogenic pain) compared to CT group (NC - 66.86±22.83s X CT - 130.17±35.83s, P0.001). NC group presented supporting higher intensity of stimulus on days 8 and 12 (24h and 72h after formalin injection) (P0.01 and P0.02 respectively). The IL-6 serum level was also significantly higher in the NC group than CT group (p0.001).These results indicate that an adhesive resin containing indomethacin-loaded nanocapsules has anti-inflammatory and nociceptive activities in a chemical model of acute inflammation. The present investigation confirms an adhesive resin with drug-loaded nanocapsules may be useful for improving therapeutic effect for adhesives to be used in deep cavities.

Background Morphine is an opioid analgesic used to relieve moderate-to-severe pain, including pain in neonates at the intensive care unit. In our previous study, we showed that repeated morphine exposure during early life could trigger long-lasting implications on the developing nervous system, such as long-term neurochemical and behavioral alterations in adult rats. Aims The aim of our study was to determine the short-, intermediate-, and long-term effects of repeated morphine administration during early life on the thermal and mechanical thresholds and on the central levels (cerebral cortex and brainstem) of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and cytokines (interleukin-6 [IL-6] and IL-10). Methods Male Wistar rats were administered morphine (5 μg/day, s.c.) or saline for 7 days from postnatal day 8 (P8) until P14. The nociceptive effect was assessed by evaluating the thermal response using the hot plate test (HPT) and the mechanical response by Von Frey (VFT) and Randall-Selitto (RST) tests at P16, P30, and P60. BDNF, NGF, IL-6, and IL-10 levels were measured in the cerebral cortex and brainstem. Results In HPT, no difference in latency was observed at P16; however, at P30 and P60, the morphine-treated group exhibited a less increase in the nociceptive threshold compared to the saline group. VFT and RST demonstrated an interaction between group and age, where the morphine group showed a less pronounced increase in latency with age, which is indicative of allodynia. In the cerebral cortex, an association between BDNF and NGF levels and age was observed, where neurotrophin level increased with age in the saline group, and decreased with age in the morphine group. In addition, IL-10 levels decreased with age in both groups; however, there was no significant difference in IL-6 levels. In the brainstem, BDNF, NGF, IL-6, and IL-10 levels increased with age. Discussion Repeated morphine exposure during neonatal life triggered alterations in the nociceptive behavior, including thermal hyperalgesia and mechanical allodynia, as well as decreased levels of BDNF and NGF in the cerebral cortex. Our study highlights the importance of extensive comprehension of the pharmacological interventions during CNS maturation.

The growing number of obese people during the past decades, makes obesity a public health matter. It is considered a disease caused by multiple factors and dependent on genetic interaction, metabolic, social, behavioral and cultural factors. Pharmacologic therapy is recommended as an adjuvant therapy for obese patients or those who are overweight, which may be associated with co-morbidities putting their lives at risk. The anti obesity drugs generally act by decreasing appetite, fat absorption by inhibiting or increasing the thermogenesis and energy consumption and also in neurotransmitter systems. Among the drugs used as diet pills, we can highlight: Sibutramine, Amfepramone, Orlistat, Caffeine, Garcinia Cambogia. Therefore, the object of this systematic literature review is to check the main classes of drugs used for weight loss, that are released for the marketing in the Brazilian pharmaceutical market, highlighting its risks and benefits. The benefits of the use of pharmacological agents is to promote increased patients adherence to dietary behavioral changes and, weight loss. However, it is important to note that all the pharmacological therapy is accompanied by adverse effects and, that these effects can put the patients’ health at risk, herbal medicines as well. The use and abuse of these drugs are very common and widespread in our society, therefore, emphasizes the importance of correct information on this topic and the fundamental role of the pharmacist on guidance for the use of these drugs.

Uliginosin B (ULI) is a natural acylphloroglucinol that has been proposed as a new molecular scaffold for developing analgesic and antidepressant drugs. Its effects seem to be due to its ability to increase monoamines in the synaptic cleft by inhibiting their neuronal uptake without binding to their respective transporters, but its exact mode of action is still unknown. Considering the importance of the purinergic system to pain transmission and its modulation by monoamines availability, the aim of this study was to investigate the involvement of adenosinergic signaling in antinociceptive effect of uliginosin B. The selective adenosine A1receptor antagonist DPCPX and the selectiveA2Aantagonist ZM 241385 prevented the effect of ULI in the hot-plate test in mice. Pretreatment with inhibitors of adenosine reuptake (dipyridamole) or adenosine deaminase (EHNA) did not affect the ULI effect. On the other hand, its effect was completely prevented by an inhibitor of ecto-5′-nucleotidase (AMPCP). This finding was confirmedex vivo, whereby ULI treatment increased AMP and ATP hydrolysis in spinal cord and cerebral cortex synaptosomes, respectively. Altogether, these data indicate that activation of A1andA2Areceptors and the modulation of ecto-5′-nucleotidase activity contribute to the antinociceptive effect of ULI.

Obesity is a disease that has become a serious public health issue worldwide, and chronic stressors, which are a problem for modern society, cause neuroendocrine changes with alterations in food intake. Obesity and chronic stress are associated with the development of cardiovascular diseases and metabolic disorders. In this study, a rat model was used to evaluate the effects of a hypercaloric diet plus chronic restraint stress on the serum leptin and lipids levels and on the weight of specific adipose tissue (mesenteric, MAT; subcutaneous, SAT and visceral, VAT). Wistar rats were divided into the following 4 groups: standard chow (C), hypercaloric diet (HD), stress plus standard chow (S), and stress plus hypercaloric diet (SHD). The animals in the stress groups were subjected to chronic stress (placed inside a 25cm×7cm plastic tube for 1h per day, 5 days per week for 6 weeks). The following parameters were evaluated: the weight of the liver, adrenal glands and specific adipose tissue; the delta weight; the Lee index; and the serum levels of leptin, corticosterone, glucose, total cholesterol, and triglycerides. The hypercaloric diet induced obesity in rats, increasing the Lee index, weight, leptin, triglycerides, and cholesterol levels. The stress decreased weight gain even in animals fed a hypercaloric diet but did not prevent a significant increase in the Lee index. However, an interaction between the independent factors (hypercaloric diet and stress) was observed, which is demonstrated by the increased serum leptin levels in the animals exposed to both protocols.

The aim of this study was to assess the effect of acute use of general anaesthetic with or without a surgical procedure, at post-natal day 14 (P14), on behavioural responses in the short-, medium- and long-term, evaluated in open field (OF) and elevated plus-maze (EPM) tests. Fourteen-day-old male Wistar rats were divided into two experimental designs (ED): inhalation and intravenous anaesthetic, and these groups were subdivided into: 1st ED - control (C), isoflurane (ISO), isoflurane/surgery (ISO-SUR); 2nd ED - control (C), fentanyl/S(+)-ketamine (FK) and fentanyl+ketamine-s/surgery (FK-SUR). In the OF the following were found: (a) in the 1st ED: an increase in the locomotor activity in the ISO group at P14, and ISO and ISO-SUR groups at P30; the ISO-SUR group showed a reduced latency to leave the first quadrant at P30 and P60; (b) in the 2nd ED: FK and FK-SUR groups presented increased locomotor activity at P30, and the FK group showed a reduction in the number of faecal boluses. In the EPM the following were found: FK and FK-SUR groups presented an increase in the number of non-protected head-dipping (NPHD) movements and in the number of entries and time spent in open arms at P30; the FK group showed an increased number of protected head-dipping movements, NPHD and entries and time spent in the open arms at P60. The behavioural changes observed may be related to locomotor activity (1st ED) and anxiety level (2nd ED) and they may result from changes in neurotransmitters/hormones (DA, 5HT, CRH) and glutamate/NMDA receptors, respectively.

Considering the importance of a deeper understanding of the effect throughout life of opioid analgesia at birth, our objective was to determine whether morphine administration in early life, once a day for 7days in 8-day-old rats, alters the nociceptive response over the short (P16), medium (P30), and long term (P60) and to evaluate which system is involved in the altered nociceptive response. The nociceptive responses were assessed by the formalin test, and the behavior analyzed was the total time spent in biting and flicking of the formalin-injected hindpaw, recorded during the first 5min (phase I) and from 15–30min (phase II). The morphine group showed no change in nociceptive response at P16, but at P30 and P60, the nociceptive response was increased in phase I, and in both phases, respectively. At P30 and P60, the animals received a non-steroidal anti-inflammatory drug (indomethacin) or NMDA receptor antagonist (ketamine) 30min before the formalin test. The increase in the nociceptive response was completely reversed by ketamine, and partially by indomethacin. These results indicate that early morphine exposure causes an increase in the nociceptive response in adult life. It is possible that this lower nociception threshold is due to neuroadaptations in nociceptive circuits, such as the glutamatergic system. Thus, this work demonstrates the importance of evaluating clinical consequences related to early opioid administration and suggests a need for a novel design of agents that may counteract opiate-induced neuroplastic changes.

Circadian rhythms represent an important mechanism to prepare the organism for environmental variations. ATP, ADP, AMP, and adenosine can act as extracellular messengers in a range of biological processes and are metabolized by a number of enzymes, including NTPDases and 5′-nucleotidase. In the present study the authors report that ATPase and ADPase activities present 24-h temporal variations that peak during dark (activity) span. These findings suggest that this enzymatic temporal pattern in blood serum might be important for the normal physiology and function of the organism through the maintenance of extracellular nucleotides at physiological levels. (Author correspondence: iracitorres@gmail.com)

Objective. The aim was to assess the neuromodulation techniques effects (repetitive transcranial magnetic stimulation [rTMS] and deep intramuscular stimulation therapy [DIMST]) on pain intensity, peripheral, and neurophysiological biomarkers chronic myofascial pain syndrome (MPS) patients. Design. Randomized, double blind, factorial design, and controlled placebo-sham clinical trial. Setting. Clinical trial in the Laboratory of Pain and Neuromodulation at Hospital de Clinicas de Porto Alegre ([NCT02381171][1]). Subjects. We recruited women aged between 19- and 75-year old, with MPS diagnosis. Methods. Patients were randomized into four groups: rTMS + DIMST, rTMS + sham-DIMST, sham-rTMS + DIMST, sham-rTMS + sham-DIMST; and received 10 sessions for 20 minutes each one (rTMS and DIMST). Pain was assessed by visual analogue scale (VAS); neurophysiological parameters were assessed by transcranial magnetic stimulation; biochemical parameters were: BDNF, S100β, lactate dehydrogenase, inflammatory (TNF-α, IL6, and IL10), and oxidative stress parameters. Results. We observed the pain relief assessed by VAS immediately assessed before and after the intervention ( P 0.05). Conclusion. Our findings add additional evidence about rTMS and DIMST in relieving pain in MPS patients without synergistic effect. No peripheral biomarkers reflected the analgesic effect of both techniques; including those related to cellular damage. Additionally, one neurophysiological parameter (increased MEP amplitude) needs to be investigated. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02381171&atom=%2Fpainmedicine%2F17%2F1%2F122.atom

IntroductionNeuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP.ObjectiveEvaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model.MethodsRats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24h (phase I) and 7days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48h (phase I) and 8days (phase II) after tDCS treatment by ELISA.ResultsThe chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P

It has been suggested that food craving-an intense desire to consume a specific food (particularly foods high in sugar and fat)-can lead to obesity. This behavior has also been associated with abuse of other substances, such as drugs. Both drugs and food cause dependence by acting on brain circuitry involved in reward, motivation, and decision-making processes. The dorsolateral prefrontal cortex (DLPFC) can be activated following evocation and is implicated in alterations in food behavior and craving. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique capable of modulates brain activity significantly, has emerged as a promising treatment to inhibit craving. This technique is considered safe and inexpensive; however, there is scant research using animal models. Such studies could help elucidate the behavioral and molecular mechanisms of eating disorders, including food craving. The aim of our study was to evaluate palatable food consumption in rats receiving tDCS treatment (anode right/cathode left). Eighteen adult male Wistar rats were randomized by weight and divided into three groups (n = 6/group): control, with no stimulation; sham, receiving daily 30 s tDCS (500 μA) sessions for 8 consecutive days; and tDCS, receiving daily 20 min tDCS (500 μA) sessions for 8 consecutive days. All rats were evaluated for locomotor activity and anxiety-like behavior. A palatable food consumption test was performed at baseline and on treatment completion (24 h after the last tDCS session) under fasting and feeding conditions and showed that tDCS decreased food craving, thus corroborating human studies. This result confirms the important role of the prefrontal cortex in food behavior, which can be modulated by noninvasive brain stimulation.

Background Estrogen deficiency is associated with the onset of depressive and anxiety symptoms, cognitive impairment, and adverse consequences. We investigated depressive-like behaviors in ovariectomized rats and ketamine's effect on this behavior. Methods Twenty-eight female Wistar adult rats were initially divided into two groups: ovariectomized (OVX) and sham surgery (SHAM). Hormonal status was verified by vaginal cytology, and the rats were subjected to a forced swimming (FS) test 18 days post-surgery, an open field (OF) test 28 days post-surgery, and an elevated plus maze (EPM) test 38 days post-surgery (Experiment 1). In addition, the effect of ketamine on depressive-like behavior of the female rats was evaluated (Experiment 2). Results OVX group exhibited anxiety-like behavior on EPM test (lower time spent and fewer entries in the open arms), without any difference in performance in the OF test. OVX rats showed depressive-like behavior (higher time of immobility) than SHAM rats in FS test. The SHAM group showed signs of hypoestrogenism (anestrus) at six months of age. Moreover, ketamine was able to reverse depressive-like behavior in the FS retest in both groups (OVX and SHAM). Conclusion Similar to the literature, we showed the antidepressant effect of ketamine in depressive female rats which was induced by ovariectomy; including in female rats submitted to sham surgery that interestingly presented a premature menopausal.

Central sensitivity syndrome (CSS) encompasses disorders with overlapping symptoms in a spectrum of structural pathology from persistent somatic nociception (eg, osteoarthritis) to absence of tissue injury such as in fibromyalgia, chronic tension-type headache, and myofascial pain syndrome. Likewise, the spectrum of the neuroplasticity mediators associated with CSS might present a pattern of clinical utility.We studied the brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukins 6 (IL-6) and IL-10 in female patients with CSS absent of structural pathology (chronic tension-type headache [n=30], myofascial pain syndrome [n=29], fibromyalgia [n=22]); with CSS due to persistent somatic/visceral nociception (osteoarthritis [n=27] and endometriosis [n=32]); and in pain-free controls (n=37).Patients with CSS absent of structural pathology presented higher serum TNF-α (28.61±12.74 pg/mL) and BDNF (49.87±31.86 ng/mL) than those with persistent somatic/visceral nociception (TNF-α=17.35±7.38 pg/mL; BDNF=20.44±8.30 ng/mL) and controls (TNF-α=21.41±5.74 pg/mL, BDNF=14.09±11.80 ng/mL). Moreover, CSS patients absent of structural pathology presented lower IL levels. Receiver operator characteristics analysis showed the ability of BDNF to screen CSS (irrespective of the presence of structural pathology) from controls (cutoff=13.31 ng/mL, area under the curve [AUC]=0.86, sensitivity=95.06%, specificity=56.76%); and its ability to identify persistent nociception in CSS patients when experiencing moderate-severe depressive symptoms (AUC=0.81; cutoff=42.83 ng/mL, sensitivity=56.80%, specificity=100%). When the level of pain measured on the visual analog scale was5 and moderate-severe depressive symptoms were observed TNF-α discriminated structural pathology in the chronic pain conditions (AUC=0.97; cutoff=22.11 pg/mL, sensitivity=90%, specificity=91.3%).Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

The aim of this study was to test and compare the effects of a within-subject design of repetitive transcranial magnetic stimulation (rTMS) [coupled with sham transcranial direct current stimulation (tDCS)] and tDCS (coupled with sham rTMS) on the motor cortex excitability and also compare the results against sham tDCS/sham rTMS. We conducted a double-blinded, randomized, sham-controlled, cross-over trial. Eleven right-handed, healthy individuals (five women, mean age: 39.8 years, SD 13.4) received the three interventions (cross-over design) in a randomized order: (a) high-frequency (HF) rTMS (+sham tDCS), (b) anodal tDCS (+sham rTMS), and (c) sham stimulation (sham rTMS+sham tDCS). Cortical excitability measurements [motor threshold, motor evoked potential (MEP), intracortical facilitation and inhibition, and transcallosal inhibition] and motor behavioral assessments were used as outcome measures. Between-group analysis of variance showed that MEP amplitude after HF rTMS was significantly higher than MEP amplitude after anodal tDCS (P=0.001). Post-hoc analysis showed a significant increase in MEP amplitude after HF rTMS (25.3%, P=0.036) and a significant decrease in MEP amplitude after anodal tDCS (-32.7%, P=0.001). There was a similar increase in motor function as indexed by Jebsen-Taylor Hand Function Test in the two active groups compared with sham stimulation. In conclusion, here, we showed that although both techniques induced similar motor gains, they induce opposing results in cortical excitability. HF rTMS is associated with an increase in corticospinal excitability, whereas 20 min of tDCS induces the opposite effect. We discuss potential implications of these results to future clinical experiments using rTMS or tDCS for motor function enhancement.

JUSTIFICATIVA E OBJETIVOS: A saliva tem um papel importante na saúde bucal; está envolvida na lubrificação da mucosa oral, na proteção contra infecções, no transporte de nutrientes e enzimas digestivas, na remineralização dentária e também auxilia na mastigação, deglutição e fala. Sabe-se que reduções na quantidade de saliva aumentam o risco de doenças bucais. Este estudo investigou os fatores associados a alterações no fluxo salivar e seu relacionamento com idade, síndrome de ardência bucal, distúrbios psiquiátricos e do sono, doenças sistêmicas e uso crônico de medicamentos. MÉTODOS: Foi incluído um total de 30 pacientes com queixa de xerostomia sem doenças sistêmicas desequilibradas. Foram aplicados questionários sobre dados sociodemográficos, xerostomia, ardência bucal, sintomas de depressão e ansiedade e distúrbios do sono. As medidas de fluxo salivar foram obtidas pelo método spit. A correlação entre hipo-salivação e dados quantitativos foi determinada por um modelo univariado de regressão. RESULTADOS: A idade various de 31;83 anos, hipo-salivação foi correlacionada positivamente com distúrbios do sono (β=0,079, 95% CI, 0,033 a 0,124) e negativamente com ardência bucal (β=-0,043, 95% CI, -0,083 a -0,002). CONCLUSÃO: Esses resultados trazem evidências sobre a associação entre fluxo salivar reduzido e ardência bucal, distúrbios do sono e uso crônico de psicotrópicos, e destacamos o importante papel dos antidepressivos na modulação da sensação de ardência bucal. BACKGROUND AND OBJECTIVES: Saliva plays an important role in oral health; it is involved in lubrication of the oral mucosa, protection against infections, transport of nutrients and digestive enzymes, remineralization of teeth, as well as aiding in chewing, swallowing and speech. Reductions in the amount of saliva are known to increase the risk of oral diseases. This study investigated the factors associated to salivary flow alterations and its relationship with age, burning mouth syndrome, psychiatric and sleep disorders, systemic diseases and chronic drug use. METHODS: A total of 30 patients complaining of dry mouth without unbalanced systemic diseases were included. Questionnaires regarding socio-demographic data, xerostomia, burning mouth, depression and anxiety symptoms, and sleep disturbances were applied. Measures of salivary flow rates were obtained using spit method. Correlation of hyposalivation and quantitative data was determined using a multivariate regression model. RESULTS: The age range was 31-83 years, hyposalivation was correlated positively with sleep disorder (β=0.079, 95% CI, 0.033 to 0,124) and negatively with burning mouth (β=-0.043, 95% CI, -0.083 to -0.002). CONCLUSION: These results provide evidences regarding the association between reduced salivary flow and burning mouth, sleep disorders and chronic use of psychotropic medicines, and we highlighted the important role of antidepressants on modulation of burning mouth sensation.