Electroacupuncture modulates cortical excitability in a manner dependent on the parameters used.

INTRODUCTION: There is evidence that electroacupuncture (EA) acts through the modulation of brain activity, but little is known about its influence on corticospinal excitability of the primary motor cortex (M1). OBJECTIVE: To investigate the influence of EA parameters on the excitability of M1 in healthy individuals. METHODS: A parallel, double blind, randomized controlled trial in healthy subjects, evaluating the influence of an EA intervention on M1 excitability. Participants had a needle inserted at LI4 in the dominant hand and received electrical stimulation of different frequencies (10 or 100 Hz) and amplitude (sensory or motor threshold) for 20 min. In the control group, only a brief (30 s) electrical stimulation was applied. Single and paired pulse transcranial magnetic stimulation coupled with electromyography was applied before and immediately after the EA intervention. Resting motor threshold, motor evoked potential, short intracortical inhibition and intracortical facilitation were measured. RESULTS: EA increased corticospinal excitability of M1 compared to the control group only when administered with a frequency of 100 Hz at the sensory threshold (p < 0.05). There were no significant changes in the other measures. CONCLUSION: The results suggest that EA with an intensity level at the sensorial threshold and 100 Hz frequency increases the corticospinal excitability of M1. This effect may be associated with a decrease in the activity of inhibitory intracortical mechanisms. TRIAL REGISTRATION NUMBER: U1111-1173-1946 (Registro Brasileiro de Ensaios Clínicos; http://www.ensaiosclinicos.gov.br/).

Neuroinflammatory effects of tDCS in ovariectomized rats with chronic inflammation

Introduction: Postmenopausal women are more susceptible to chronic conditions, such as osteoporosis, arthritis, and other inflammatory diseases. We investigated the effects of transcranial direct current stimulation (tDCS) on biomarker levels in ovariectomized rats subjected to an inflammatory model. Methods: Twenty adult female Wistar rats underwent ovariectomy and complete Freund's adjuvant (CFA)-induced inflammation. We divided them into 2 groups: OAS (sham tDCS) and OAT (active tDCS). Fifteen days later, the rats underwent bimodal tDCS treatment (20 min, 0.5 mA, 8 days). After 24 h of the last tDCS session, we killed the rats and collected tissue samples (hypothalamus, cerebral cortex, and brainstem) for biomarker analysis by ELISA. We removed the paws for histological analysis. Results: Active tDCS increased hypothalamic and cortical TNF-α and NGF levels, hypothalamic and brainstem IL-1ß levels, and hypothalamic IL-10 levels. Histology of paws showed an inflammatory profile. We observed a small tDCS effect, not statistically significant. Discussion: Bimodal tDCS had an effect on the central inflammatory axis, with a small effect on the peripheral site as evaluated by histology in the current study. (AU)

Neonatal morphine exposure and maternal deprivation alter nociceptive response and central biomarkers' levels throughout the life of rats.

In the present study, we investigated the effect of repeated neonatal morphine exposure and/or maternal deprivation(MD) on the nociceptive response and central biomarkers' BDNF, IL-1ß, and IL-4 levels at postnatal days 16(PND16), 30(PND30), and 60(PND60). At birth, the litters were standardized to contain 8 pups/dam (n = 58). From PND1 to PND10, the pups of the deprived groups were separated daily from their mothers for 3 h and divided into 5 groups: control(C), saline(S), morphine(M), deprived-saline(DS), and deprived-morphine(DM). The pups received subcutaneous injections of saline/morphine (5 µg) in the mid-scapular area between PND8 and PND14. Nociceptive responses were assessed by hot plate(HP) and tail-flick(TFL) tests and biomarker levels by ELISA. Thermal hyperalgesia(HP) was found in all assessments for the M, DS, and DM groups, and a decrease in nociceptive threshold(TFL) was found in the DS group at PND16; M and DM groups at PND30; and M, DS, and DM groups at PND60. There were interactions between treatment/deprivation/timepoint in all central biomarkers' levels. The current study indicates that neonatal exposure to morphine and MD, which occurs in the pediatric ICU, can alter the nociceptive and neuroinflammatory responses.

Home-Based Transcranial Direct Current Stimulation Device Development: An Updated Protocol Used at Home in Healthy Subjects and Fibromyalgia Patients.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation (NIBS) method, which modulates the membrane potential of neurons in the cerebral cortex by a low-intensity direct current. tDCS is a low-cost technique with minimal adverse effects and easy application. This neurostimulation method has a promising future to improve pain therapy, treatment of neuropsychiatric disorders, and physical rehabilitation. Current studies demonstrate the benefits of using tDCS over consecutive multiple sessions. However, the daily displacement to the specialized centers, travel costs, and disruptions to daily activities are some of the difficulties faced by patients. Thus, to be more comfortable, easy-to-use, and not disrupt daily commitments, a home-based tDCS was designed. Therefore, the objective of this study was to evaluate the feasibility of a portable tDCS device for home use in healthy subjects and fibromyalgia patients. Despite increased tDCS use and a reasonably large body of research on the effects across a range of clinical conditions, there is a limited amount of research on developing secure devices that guarantee the dose and contain a block system to avoid excessive use. Therefore, we used a tDCS device with a security system to permit daily use for 20 minutes with a minimal interval of 12 hours between sessions. A programmer preconfigures the equipment, which has a neoprene cap that allows the electrode positions in any assembly, according to individualized protocols for treatments or research. After, researchers can assess the effectiveness of treatment, and its adherence using information kept in the device software. Results suggest that the device is feasible for home use, with proper monitoring of adherence and contact impedance. There were reports of a few adverse effects, which do not differ from those reported in the literature in studies with the treatment under direct supervision.

Preclinical to Clinical Translation of Studies of Transcranial Direct-Current Stimulation in the Treatment of Epilepsy: A Systematic Review.

Epilepsy is a chronic brain syndrome characterized by recurrent seizures resulting from excessive neuronal discharges. Despite the development of various new antiepileptic drugs, many patients are refractory to treatment and report side effects. Non-invasive methods of brain stimulation, such as transcranial direct current stimulation (tDCS), have been tested as alternative approaches to directly modulate the excitability of epileptogenic neural circuits. Although some pilot and initial clinical studies have shown positive results, there is still uncertainty regarding the next steps of investigation in this field. Therefore, we reviewed preclinical and clinical studies using the following framework: (1) preclinical studies that have been successfully translated to clinical studies, (2) preclinical studies that have failed to be translated to clinical studies, and (3) clinical findings that were not previously tested in preclinical studies. We searched PubMed, Web of Science, Embase, and SciELO (2002-2017) using the keywords "tDCS," "epilepsy," "clinical trials," and "animal models." Our initial search resulted in 64 articles. After applying inclusion and exclusion criteria, we screened 17 full-text articles to extract findings about the efficacy of tDCS, with respect to the therapeutic framework used and the resulting reduction in seizures and epileptiform patterns. We found that few preclinical findings have been translated into clinical research (number of sessions and effects on seizure frequency) and that most findings have not been tested clinically (effects of tDCS on status epilepticus and absence epilepsy, neuroprotective effects in the hippocampus, and combined use with specific medications). Finally, considering that clinical studies on tDCS have been conducted for several epileptic syndromes, most were not previously tested in preclinical studies (Rasmussen's encephalitis, drug resistant epilepsy, and hippocampal sclerosis-induced epilepsy). Overall, most studies report positive findings. However, it is important to underscore that a successful preclinical study may not indicate success in a clinical study, considering the differences highlighted herein. Although most studies report significant findings, there are still important insights from preclinical work that must be tested clinically. Understanding these factors may improve the evidence for the potential use of this technique as a clinical tool in the treatment of epilepsy.

Isoflurane and the Analgesic Effect of Acupuncture and Electroacupuncture in an Animal Model of Neuropathic Pain.

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 ß (S100ß) 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 S100ß levels and NGF levels in the left sciatic nerve. Isoflurane enhanced the analgesic effects of Ac and EA and altered serum S100ß and left sciatic nerve NGF levels in rats with NP.

Morphine exposure and maternal deprivation during the early postnatal period alter neuromotor development and nerve growth factor levels.

The objective of this study was to verify whether repeated morphine administration and maternal deprivation in early life alter neurobehavioral development and central nerve growth factor (NGF) levels. A total of 58 male Wistar rat pups were used in our study. From postnatal day 1 (P1), litters were daily deprived of their mother for 3h; this was continued for the first 10days of life. Animals were divided into 5 groups: total control (C), did not receive any intervention; saline (S), received saline solution; morphine (M), received morphine; deprived-saline group (DS), were subjected to maternal deprivation and received saline solution; and deprived-morphine (DM), were subjected to maternal deprivation and received morphine. From P8, newborns received subcutaneous (s.c.) injections of morphine or saline (5µg) once daily for 7days. Righting reflex, negative geotaxis and gait were chosen as postural parameters to evaluate neuromotor reflexes. In the righting reflex test, a delay in the development of animals was evidenced in the M group. Performance of negative geotaxis was slower in the M and DM groups. In the gait test, all groups showed a daily improvement in performance in terms of locomotion frequency. An increased frequency of rearing was observed in the M, DS, and DM groups from P16 to P20. The DM group presented an increase in NGF levels in the brainstem. An increase in cerebral cortex NGF levels in the M, DS, and DM groups was observed as well. Our results suggest that changes in environmental conditions and the disruption of mother-infant interactions during the neonatal period can produce changes in the neurobiology, physiology, and emotional behavior of rats. This finding has important implications for the maternal-neonate interaction needed for normal brain development in newborns.

Evaluation of different procedure involved in the Transcranial Direct Current Stimulation (tDCS) technique experimental application

Introduction: The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in the central nervous system of animals and humans. Furthermore, tDCS has been suggested as a therapeutic tool for pain management. The aim of this study was to standardize a non-invasive tDCS technique indexed by the nociceptive response of rats submitted to different conditions necessary to the tDCS application. Method: 60-day-old male Wistar rats (n=65), divided into 6 groups: control(C); non-active sham (NAS); active-sham (AS); active-sham restrained (ASR); non-active sham restrained (NASR); active tDCS treatment. Animals received treatment during 30 seconds (sham-active) or 20 minutes (restraint and tDCS)/8 days. Nociceptive threshold was assessed by Hot Plate test at baseline, immediately and 24h after the first session, immediately and 24h after the last session. Variance analysis of repeated measurements followed by Bonferroni was performed for intra-group comparison. Results: Physical restraint and 30 seconds stimulation (sham-tDCS) increased pain sensitivity (P≤0.05), and tDCS treatment was able to prevent the thermal hyperalgesia. Our original tDCS montage is similar to that used in the procedure with humans, because it is not an invasive technique. The electrodes are positioned on the head, and the animals are immobilized during the 20-minute treatment. As this procedure could involve behavior and neurochemical alterations due to stress induced by restriction (thus, it creates a research bias), we hypothesized that a 30-second electrical stimulus application (sham-tDCS) and the physical restriction used during tDCS treatment might alter nociceptive response in rats. Conclusion: There are methodological limitations in the present tDCS-technique. Although active-tDCS treatment is able to prevent these harmful effects, interference of these factors has to be considered during the results' analysis. Future adaptations of the tDCS-technique in rats are required to evaluate its therapeutic effects (AU)

Descending Control of Nociceptive Processing in Knee Osteoarthritis Is Associated With Intracortical Disinhibition: An Exploratory Study.

Based on the hypothesis that an imbalance in excitatory and inhibitory input is a central mechanism of knee osteoarthritis chronic pain (KOACP), this exploratory study had the following aims: to compare whether the function of the descending inhibitory pain pathway is associated with the state of inhibition in the corticospinal system indexed by the motor-evoked potential (MEP) and the cortical salient period (CSP) in patients with severe osteoarthritis (OA) and healthy controls; and to determine if there is correlation between the measures of intracortical inhibition (CSP, MEP) with changes on the numerical pain scale (NPS [0-10]) in KOACP during a conditioned pain modulation (CPM)-task considering the effect of self-reported function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and analgesic use.In a cross-sectional study, we included females (n = 21), with disability by pain or stiffness due to KOACP and healthy controls (n = 10), aged 19 to 75 years. The motor cortex excitability parameters (MEP and CSP) were assessed using the transcranial magnetic stimulation. We assessed the pain and disability by the WOMAC, and change on NPS (0-10) during CPM-task.A Multivariate analysis of covariance revealed that the adjusted mean (SD) on the MEP amplitude was 13.53% higher in the OA than in healthy subjects (1.33 [0.49] vs 1.15 [0.13]), respectively (P = 0.16). The adjusted mean (SD) on the CSP observed in OA patients was 23.43% lower than in healthy subjects (54.54 [16.10] vs 70.94 [22.87]), respectively (P = 0.01). The function of the descending pain modulatory system assessed by change on NPS (0-10) during a CPM-task was negatively correlated with the cortical excitability parameter indexed by the CSP (P = 0.001). Also, the CSP was negatively correlated with the pain and disability assessed by the WOMAC index.These findings support the hypothesis that the change in cortical plasticity in KOACP is associated with less intracortical inhibition, as measured by the CSP. These results show that the neural change in the motor cortex in KOACP is associated with pain and disability levels, and also with decreased activation of the endogenous pain-modulating system by a CPM-task.

Long-Lasting Effect of Transcranial Direct Current Stimulation in the Reversal of Hyperalgesia and Cytokine Alterations Induced by the Neuropathic Pain Model.

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-1ß, 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-1ß, 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.

Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect.

INTRODUCTION: Neuropathic 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. OBJECTIVE: Evaluate 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. METHODS: Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. RESULTS: The 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<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). CONCLUSION: tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations.

Effect of Deep Intramuscular Stimulation and Transcranial Magnetic Stimulation on Neurophysiological Biomarkers in Chronic Myofascial Pain Syndrome.

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 Clínicas de Porto Alegre (NCT02381171). 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, S100ß, 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, F(1,3)= 3.494 and F(1,3)= 4.656, respectively); in the sham-rTMS + DIMST group and both three active groups in relation to sham-rTMS + sham-DIMST group, respectively. There was an increase in the MEP after rTMS + sham-DIMST (P < 0.05). However, there was no change in all-peripheral parameters analyzed across the treatment (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.

Hypercaloric diet modulates effects of chronic stress: a behavioral and biometric study on rats.

Obesity is a chronic disease that has been associated with chronic stress and hypercaloric diet (HD) consumption. Increased ingestion of food containing sugar and fat ingredients (comfort food) is proposed to "compensate" chronic stress effects. However, this eating habit may increase body fat depositions leading to obesity. This study evaluated behavioral/physiological parameters seeking to establish whether there is an association between the effects of HD intake and stress, and to test the hypothesis that the development of anxious behavior and obesity during chronic stress periods depends on the type of diet. Sixty-day-old male Wistar rats (n = 100) were divided into four groups: standard chow, hypercaloric diet, chronic stress/standard chow and chronic stress/hypercaloric diet. Chronic stress was induced by restraint stress exposure for 1 h/day, for 80 d. At the end of this period, rat behavior was evaluated using open-field and plus-maze tests. The results showed that HD alone increased weight gain and adipose deposition in subcutaneous and mesenteric areas. However, stress reduced weight gain and adipose tissue in these areas. HD also increased naso-anal length and concurrent stress prevented this. Behavioral data indicated that stress increased anxiety-like behaviors and comfort food reduced these anxiogenic effects; locomotor activity increased in rats fed with HD. Furthermore, HD decreased corticosterone levels and stress increased adrenal weight. The data indicate that when rats are given HD and experience chronic stress this association reduces the pro-obesogenic effects of HD, and decreases adrenocortical activity.

Electroacupuncture analgesia is associated with increased serum brain-derived neurotrophic factor in chronic tension-type headache: a randomized, sham controlled, crossover trial.

BACKGROUND: Chronic tension-type headache (CTTH) is characterized by almost daily headaches and central sensitization, for which electroacupuncture (EA) might be effective. The central nervous system (CNS) plasticity can be tracked in serum using the brain-derived neurotrophic factor (BDNF), a neuroplasticity mediator. Thus, we tested the hypothesis that EA analgesia in CTTH is related to neuroplasticity indexed by serum BDNF. METHODS: We enrolled females aged 18-60 years with CTTH in a randomized, blinded, placebo-controlled crossover trial, comparing ten EA sessions applied for 30 minutes (2-10 Hz, intensity by tolerance) in cervical areas twice per week vs. a sham intervention. Treatment periods were separated by two washout weeks. Pain on the 10-cm visual analog scale (VAS) and serum BDNF were assessed as primary outcomes. RESULTS: Thirty-four subjects underwent randomization, and twenty-nine completed the protocol. EA was superior to sham to alleviate pain (VAS scores 2.38 ± 1.77 and 3.02 ± 2.49, respectively, P = 0.005). The VAS scores differed according to the intervention sequence, demonstrating a carryover effect (P < 0.05). Using multiple regression, serum BDNF was adjusted for the Hamilton depression rating scale (HDRS) and the VAS scores (r-squared = 0.07, standard ß coefficients = -0.2 and -0.14, respectively, P < 0.001). At the end of the first intervention period, the adjusted BDNF was higher in the EA phase (29.31 ± 3.24, 27.53 ± 2.94 ng/mL, Cohen's d = 0.55). CONCLUSION: EA analgesia is related to neuroplasticity indexed by the adjusted BDNF. EA modulation of pain and BDNF occurs according to the CNS situation at the moment of its administration, as it was related to depression and the timing of its administration.

Effectiveness of acupuncture combined with rehabilitation for treatment of acute or subacute stroke: a systematic review.

OBJECTIVES: To determine whether the combination of acupuncture and rehabilitation produces better results in the treatment of acute or subacute stroke sequelae than rehabilitation alone. METHODS: A systematic review was carried out. A search was conducted in March 2014 using PubMed, Medline, the Cochrane Library, Chinese National Knowledge Infrastructure database (CNKI) and Wanfang databases. English and Chinese language articles published within 10 years of the search were reviewed for inclusion. Randomised control trials comparing combined treatment with acupuncture and rehabilitation and rehabilitation alone in patients with acute or subacute stroke (onset until 3 months after stroke) were included in this review. Three review authors independently checked the titles and abstracts of trials for inclusion based on selection criteria. Studies measuring changes of motor function, activities of daily living, neurological deficit or spasticity/range of motion during the treatment period and at the end of follow-up were included. RESULTS: 17 trials met the inclusion criteria, of which five were of good quality. 14 trials had results favourable to acupuncture combined with rehabilitation, compared with conventional rehabilitation treatment alone. CONCLUSIONS: Acupuncture in combination with rehabilitation may have benefits for the treatment of acute and subacute stroke sequelae in comparison with rehabilitation alone. However, many of the studies were at risk of bias. Future studies should focus on reaching a consensus about the most appropriate modality of acupuncture intervention, and the appropriate length of treatment for both interventions, to maximise the potential synergistic outcomes.

Factors associated to salivary flow alterations in dry mouth female patients / Fatores associados a alterações no fluxo salivar em pacientes com xerostomia

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, 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...

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...

Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy, controlled trial.

BACKGROUND: Central disinhibition is a mechanism involved in the physiopathology of fibromyalgia. Melatonin can improve sleep quality, pain and pain threshold. We hypothesized that treatment with melatonin alone or in combination with amitriptyline would be superior to amitriptyline alone in modifying the endogenous pain-modulating system (PMS) as quantified by conditional pain modulation (CPM), and this change in CPM could be associated with serum brain-derived neurotrophic factor (BDNF). We also tested whether melatonin improves the clinical symptoms of pain, pain threshold and sleep quality. METHODS: Sixty-three females, aged 18 to 65, were randomized to receive bedtime amitriptyline (25 mg) (n = 21), melatonin (10 mg) (n = 21) or melatonin (10 mg) + amitriptyline (25 mg) (n = 21) for a period of six weeks. The descending PMS was assessed with the CPM-TASK. It was assessed the pain score on the Visual Analog Scale (VAS 0-100 mm), the score on Fibromyalgia Impact Questionnaire (FIQ), heat pain threshold (HPT), sleep quality and BDNF serum. Delta values (post- minus pre-treatment) were used to compare the treatment effect. The outcomes variables were collected before, one and six weeks after initiating treatment. RESULTS: Melatonin alone or in combination with amitriptyline reduced significantly pain on the VAS compared with amitriptyline alone (P < 0.01). The delta values on the VAS scores were-12.85 (19.93),-17.37 (18.69) and-20.93 (12.23) in the amitriptyline, melatonin and melatonin+amitriptyline groups, respectively. Melatonin alone and in combination increased the inhibitory PMS as assessed by the Numerical Pain Scale [NPS(0-10)] reduction during the CPM-TASK:-2.4 (2.04) melatonin + amitriptyline,-2.65 (1.68) melatonin, and-1.04 (2.06) amitriptyline, (P < 0.05). Melatonin + amitriptyline treated displayed better results than melatonin and amitriptyline alone in terms of FIQ and PPT improvement (P < 0.05, fort both). CONCLUSION: Melatonin increased the inhibitory endogenous pain-modulating system as assessed by the reduction on NPS(0-10) during the CPM-TASK. Melatonin alone or associated with amitriptyline was better than amitriptyline alone in improving pain on the VAS, whereas its association with amitriptyline produced only marginal additional clinical effects on FIQ and PPT. TRIAL REGISTRATION: Current controlled trail is registered at clinical trials.gov upon under number NCT02041455. Registered January 16, 2014.

Effects of acupuncture on the symptoms of anxiety and depression caused by premenstrual dysphoric disorder.

OBJECTIVE: The objective of this investigation was to evaluate the effects of acupuncture and sham acupuncture on the symptoms of anxiety and depression brought on by premenstrual dysphoric disorder (PMDD). METHODS: In a single-blind randomised clinical trial, 30 volunteers with PMDD were assigned alternately to group 1 (acupuncture) or group 2 (sham acupuncture), and completed an evaluation of symptoms of anxiety and depression using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. The procedure was performed twice a week for two menstrual cycles, for a total of 16 attendances for each participant. RESULTS: Before the intervention the mean HAM-A and HAM-D scores did not differ between groups. Following the intervention symptoms of anxiety and depression were reduced in both groups; however, the improvement was significant in group 1 compared to group 2, as shown by a mean reduction in HAM-A scores of 58.9% in group 1 and 21.2% in group 2 (p<0.001). The reduction in the mean HAM-D scores was 52.0% in group 1 and 19.6% in group 2, resulting in a significant difference (p=0.012). CONCLUSIONS: The results suggest that acupuncture could be another treatment option for PMDD patients.

Skin vasodilation and analgesic effect of a topical nitric oxide-releasing hydrogel.

New approaches based on topical treatments are needed for treating pain and impaired dermal blood flow. We used a topical Pluronic F127 hydrogel containing S-nitrosoglutathione (GSNO) as a prodrug to generate free NO, an effector molecule that exerts both dermal vasodilation and antinociceptive effects. GSNO-containing hydrogels underwent gelation above 12 °C and released free NO at rates that were directly dependent on the GSNO concentration in the range of 50-150 mM. The topical application of this material led to dose-response dermal vasodilation in healthy volunteers and to a reduction of up to 50 % of the hypernociception intensity in Wistar rats that were subjected to inflammatory pain. Mechanistic investigations indicated that the antinociceptive effect of the topical F127/GSNO hydrogels is produced by the local activation of the cGMP/PKG/KATP channel-signaling pathway, which was stimulated by the free NO that diffused through the skin. These results expand the scope of the biomedical applications of this material and may represent a new approach for the topical treatment of inflammatory pain.

Auriculoterapia associada à placa miorrelaxante no alívio da dor em indivíduos com desordens temporomandibulares: estudo piloto / Auriculotherarpy associated with the card relaxant pain relief in subjects with temporomandibular disorders: pilot study

A sensibilidade muscular é um sinal clínico importante presente na maioria dos pacientes com algum tipo de Disfunção Têmporo-Mandibular(DTM). A Organização Mundial de Saúde (OMS) reconheceu a auriculoterapia como uma terapia eficaz em alívio de dores. O objetivo deste trabalho é avaliar a eficiência da auriculoterapia, associada com a placa miorrelaxante, no alivio da dor em pacientes com desordens temporomandibulares comparando os grupos quanto ao tipo de seleção de pontos, tempo de tratamento e de alta. Foram analisados 15 pacientes divididos igualmente em 3 grupos: controle, grupo dos pontos pré-selecionados e grupo das síndromes energéticas. Em todos os grupos, os pacientes utilizaram placas miorrelaxantes e nos dois últimos foi realizada a auriculoterapiacom sementes. Mensurou-se o nível de dor por uma escala visual analógica(VAS). A comparação das intensidades de dor no três grupos em cada momento de medida semanal foi realizada pelo teste Kruskal-Wallis e quando houve diferenças estatisticamente significativas entre os grupos, o Teste de Mann- Whitney foi utilizado. Além disso, o tempo de tratamento para alta nos três grupos foi descrito pelas curvas de Kaplan – Maier, e comparados pelo teste log rank. Os resultados revelaram diferenças estatisticamente significantes (p<0,05) entre os grupos controle e pontos pré-selecionados, não houve diferenças entre os três grupos quanto ao tempo de alta, a associação das técnicas da auriculoterapia com a placa miorrelaxante é positiva, quando indicada para alivio da dor.

Muscular sensitivity is an important clinical sign present in the majority of patients with some type of temporomandibular dysfunction (TMD). The World Health Organization (WHO) has recognized auriculotherapy as an efficient therapy for pain relief.The aim of this study is to assess the efficiency of auriculotherapy associated with a myorelaxant plate in pain relief of patients with temporomandibular disorders, comparing the groups with regard to the type of point selection, treatment time and discharge.Fifteen patients, equally divided into 3 groups were analyzed: control, group of pre-selected points and group of energysyndromes. In all groups, the patients used myorelaxant plates, and in the latter two groups auriculotherapy with ear seeds wasperformed. The pain level was measured by a visual analogue scale (VAS). Every week the pain intensities in the three groups were measured, and all the times of these weekly pain intensity measurements were compared by the Kruskal-Wallis test. When there were statistically significant differences among the groups, the Mann- Whitney test was used. In addition, treatment time for discharge in the three groups was described by Kaplan-Meier curves and compared by the log rank test. The results revealed statistically significant differences (p<0.05) between control group and group of pre-selected points; there were no differences among the three groups as regards discharge time; the association of auriculotherapy techniques with the myorelaxant plate is positive when indicated for pain relief.