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Transcranial direct current stimulation (tDCS) has been suggested as a therapeutic tool for pain syndromes. Although initial results in human subjects are encouraging, it still remains unclear whether the effects of tDCS can reverse maladaptive plasticity associated with chronic pain. To investigate this question, we tested whether tDCS can reverse the specific behavioral effects of chronic stress in the pain system, and also those indexed by corticosterone and interleukin-1β levels in serum and TNFα levels in the hippocampus, in a well-controlled rat model of chronic restraint stress (CRS). Forty-one adult male Wistar rats were divided into two groups control and stress. The stress group was exposed to CRS for 11 weeks for the establishment of hyperalgesia and mechanical allodynia as shown by the hot plate and von Frey tests, respectively. Rats were then divided into four groups control, stress, stress+sham tDCS and stress+tDCS. Anodal or sham tDCS was applied for 20min/day over 8 days and the tests were repeated. Then, the animals were killed, blood collected and hippocampus removed for ELISA testing. This model of CRS proved effective to induce chronic pain, as the animals exhibited hyperalgesia and mechanical allodynia. The hot plate test showed an analgesic effect, and the von Frey test, an anti-allodynic effect after the last tDCS session, and there was a significant decrease in hippocampal TNFα levels. These results support the notion that tDCS reverses the detrimental effects of chronic stress on the pain system and decreases TNFα levels in the hippocampus., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Catastrophizing is a maladaptive response to pain and is one of the factors that contribute to the chronicity of some pain syndromes. The Pain Catastrophizing Scale (PCS) assists both treatment planning and outcome assessment. Its use is limited in Portuguese-speaking countries because of the lack of a validated translated version. We conducted the validation of the Brazilian Portuguese (BP)-PCS and explored its psychometric properties. This study reports the internal consistency, factor structure, and its capability to discriminate pain reported by patients with specific chronic pain conditions., Methods: Three hundred eighty-four patients, 317 women (82.55%), aged 18-79 years with chronic nonmalignant pain attending an outpatient multidisciplinary pain center participated in this cross-sectional study. The instruments were the BP-PCS, pain intensity, pain interference in functional capacity, and a sociodemographic questionnaire. One subsample with chronic tensional headache (CTH) according to the criteria of the International Headache Society (N = 19), and another with a diagnosis of fibromyalgia according to the American College of Rheumatology criteria (N = 50) were selected to assess the discriminative properties of BP-PCS., Results: We observed good internal consistency (Cronbach's α values of 0.91 for the total BP-PCS, and 0.93 [helplessness], 0.88 [magnification], and 0.86 [rumination] for the respective subdomains). The item-total correlation coefficients ranged from 0.91 to 0.94. Confirmatory factor analysis (CFA) supported the three factors structure, with the comparative fit index = 0.98, root mean square error of approximation = 0.09, and normed fit index = 0.98. Significant correlations were found for pain intensity, pain interference, and patient's mood (correlation coefficients ranged from 0.48 to 0.66, P < 0.01). No significant gender difference was observed for BP-PCS scores. When comparing scores of BP-PCS scale and subscales between the selected control group (patients with pain scores on visual analog scale equal or lower than 40 mm in the most part of the day in the last 6 months) and patients with fibromyalgia or CTH, we observed lower scores for the former group., Conclusion: Our findings support the validity and reliability of the BP-PCS. The scale showed satisfactory psychometric properties. CFA provides support for the three-factor structure reported in previous studies. This factor structure presented good discriminative properties to identify catastrophizers who present with mild chronic pain, fibromyalgia, and CTH. The BP-PCS is a valuable tool for use in scientific studies and in the clinical setting in patients with chronic pain in Brazilian Portuguese-speaking countries., (Wiley Periodicals, Inc.)

Morphine exposure during the neonatal period can promote changes in pain signaling pathways that can be expressed as an increased nociceptive response in adult life. Glutamate is the major excitatory neurotransmitter in primary afferent terminals and plays a critical role in normal spinal excitatory synaptic transmission. Considering the importance of a better understanding of the mechanisms that underlie nociceptive changes throughout the life course, the aim of this study was investigate the effects of repeated morphine administration at postnatal days 8 (P8) to 14 (P14) on glutamate uptake in spinal synaptosomes at P30 and P60. The morphine group showed decreased [3H]-glutamate uptake as compared to control groups in both P30 and P60. These findings suggest that morphine exposure in early life leads to changes in glutamatergic signaling at least until the 60th day of age, which may lead to increased levels of glutamate in the spinal synaptic cleft and, consequently, an increased nociceptive response in adult life. Thus, this study highlights the importance of conducting research in this field to provide a comprehensive knowledge of the long-term effects of early-life morphine treatment on nociceptive pathways., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

Transcranial direct current stimulation (tDCS) induces cortical excitability changes in animals and humans that can last beyond the duration of stimulation. Preliminary evidence suggests that tDCS may have an analgesic effect; however, the timing of these effects, especially when associated with consecutive sessions of stimulation in a controlled animal experiment setting, has yet to be fully explored. To evaluate the effects of tDCS in inflammatory chronic pain origin immediately and 24 h after the last treatment session, complete Freund's adjuvant (CFA) was injected (100 μl) in the right footpad to induce inflammation. On the 15th day after CFA injection, rats were divided into two groups: tDCS (n = 9) and sham (n = 9). The tDCS was applied for 8 days. The hot plate and Von Frey tests were applied immediately and 24 h after the last tDCS session. Eight 20-min sessions of 500 μA anodal tDCS resulted in antinociceptive effects as assessed by the hot plate test immediately (P = 0.04) and 24 h after the last tDCS session (P = 0.006), for the active tDCS group only. There was increased withdrawal latency in the Von Frey test at 24 h after the last session (P = 0.01). Our findings confirm the hypothesis that tDCS induces significant, long-lasting, neuroplastic effects and expands these findings to a chronic pain model of peripheral inflammation, thus supporting the exploration of this technique in conditions associated with chronic pain and peripheral inflammation, such as osteoarthritis.

BDNF is an important marker of neuronal plasticity. It has also been associated with pain processing. Increased BDNF levels are observed in chronic pain syndromes. In order to understand the role of BDNF associated with other factors such as gender on experimental pain we aimed to determine whether experimental heat or pressure pain threshold is correlated with brain derived neurotrophic factor (BDNF) level, gender and age. Heat pain threshold and pressure pain threshold were measured in 49 healthy volunteers (27 females). The multivariate linear regression models (on heat and pressure pain thresholds) revealed a significant effect of gender (p=0.001 for both models), serum BDNF (p<0.004 for both models) and interaction between BDNF and gender (<0.001 for both models). In fact, when adjusting for BDNF levels and age, heat and pressure pain thresholds were significantly reduced in women as compared to men (p<0.001 for both models). These effects were not observed when gender was analyzed alone. These finding suggests that experimental heat and pressure pain threshold is gender-related and BDNF dependent. In fact BDNF has a facilitatory effect on pain threshold in females but has an opposite effect in males; supporting the notion that BDNF is an effect modifier of the gender effects on pain threshold in healthy subjects., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Considering the importance of studies in animal models that are focused on systems involved in pain mechanisms, this investigation aimed to evaluate the effects of pharmacological treatments on the behavioral responses of younger animals. To this end, we evaluated the effect of an acute dose of fentanyl (FEN) or S(+)-ketamine (KET) at postnatal day 14 (P14) upon behavioral responses in the short- (P14), medium- (P30) and long-term (P60) using the open field (OF), elevated plus-maze (EPM) and formalin tests (FT) and tail-flick latency. Fourteen-day-old male Wistar rats were divided into three groups: control (CT), fentanyl (FEN) and S(+)ketamine (KET) groups for statistical analysis, it was performed two-way ANOVA followed by Bonferroni. We found that, regardless of the test performed (OF or EPM), between-group differences occurred over time in all behaviors analyzed, including in the second phase of FT. In addition, EPM showed significant differences in behavioral responses related to acute administration (at P14) of fentanyl or S(+)-ketamine, in behaviors such as number of entries in open and closed arms, time spent in open and closed arms, and number of head-dipping. In relation to nociceptive response, the FEN group exhibited a decrease in the first phase of FT. These results indicate that unique administration of fentanyl or S(+)ketamine in an early period of life (P14) can promote changes in behavioral responses. In addition, our findings highlight the importance of extending the investigation of the effect of drug administration in young rats into adulthood., (Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.)

Quantitative sensory testing (QST) is defined as the determination of thresholds for sensory perception under controlled stimulus. Our aim was to validate a new QST device for Brazilian sample. In 20 healthy adults, thermoalgesic thresholds were assessed using a QST prototype (Heat Pain Stimulator-1.1.10; Brazil). A 30 × 30 mm(2) thermode with a 1°C/s stimulus change rate were applied. Thresholds of three consecutive stimuli were averaged in two different sessions separated by at least two weeks. Additionally long thermal heat pain stimulus was performed. To evaluate the consistency of our method we also analyzed 11 patients with small fiber neuropathy. Results showed good reproducibility of thermal perception thresholds in normal individuals and plausible abnormal thresholds in patients. We conclude that our QST device is reliable when analyzing the nociceptive pathway in controls and patients.

In public health, mood disorders are among the most important mental impairments. Patients with depressive episodes exhibit daily mood variations, abnormal patterns in sleep-wake behavior, and in the daily rhythms of several endocrine-metabolic parameters. Although the relationship between the sleep/circadian processes and mood disorders is poorly understood, clock-related therapies, such as light therapy, sleep deprivation, and rigid sleep schedules, have been shown to be effective treatments. Several studies investigated the relationship between circadian phenotype (chronotype) and depression. These focused mainly on urban populations and assessed diurnal preferences (Morningness-Eveningness score) rather than the actual timing of sleep and activity. Here, we used the Beck Depression Inventory (BDI) in an essentially rural population (N?=?4051), and investigated its relation to circadian phenotype (chronotype and social jetlag), assessed with the Munich Chronotype Questionnaire (MCTQ). In our study design, we (i) normalized both chronotype and BDI scores for age and sex (MSF(sas) and BDI(as), respectively); (ii) calculated individual social jetlag (misalignment of the biological and social time); and (iii) investigated the relationship between circadian phenotypes and BDI scores in a population homogeneous in respect to culture, socioeconomic factors, and daily light exposure. A 15.65% (N?=?634) of the participants showed mild to severe depressive BDI scores. Late chronotypes had a higher BDI(as) than intermediate and early types, which was independent of whether or not the participants were smokers. Both chronotype and BDI(as) correlated positively with social jetlag. BDI(as) was significantly higher in subjects with >2?h of social jetlag than in the rest of the population?again independent of smoking status. We also compared chronotype and social jetlag distributions between BDI categories (no symptoms, minimal symptoms, and mild to severe symptoms of depression) separately for men and women and for four age groups; specifically in the age group 31?40 yrs, subjects with mild to severe BDI scores were significantly later chronotypes and suffered from higher social jetlag. Our results indicate that misalignment of circadian and social time may be a risk factor for developing depression, especially in 31- to 40-yr-olds. These relationships should be further investigated in longitudinal studies to reveal if reduction of social jetlag should be part of prevention strategies. (Author correspondence: karla.allebrandt@med.uni-muenchen.de ).

Background: Neuropathic pain (NP) is a very frequent and unrecognized condition in clinical practice. Therefore, it is important to have a reliable instrument to assess pain subtypes in various cultures. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) has been widely used and validated in many countries. Up to now, there has been no reliability study of this instrument in Brazil., Methods: The scores of the Brazilian Portuguese version of the LANSS were studied in a sample of 90 chronic pain outpatients from southern Brazil. LANSS was translated into Portuguese and then back translated to English. Intraclass correlation coefficient (ICC) and internal consistency (IC) were estimated. The intensity of pain complaints, other demographic data, and LANSS scores distribution according to pain subtypes (nociceptive, neuropathic, and mixed) were also evaluated., Results: The Brazilian Portuguese version of the LANSS showed good ICC (r = 0.97) and IC (Cronbach's α = 0.67 for total LANSS score). Patients with NP provided significant higher LANSS scores (19.1 ± 3.3) in comparison with those with nociceptive (7.3 ± 4.5) and mixed (13.9 ± 3.7) types of pain., Conclusions: This LANSS version was found to be a reliable instrument for the evaluation of pain complaints due to a variety of causes. The profile of pain scores was similar to that observed in other countries., (Wiley Periodicals, Inc.)

Background: Adenosine 5-triphosphate (ATP) and its breakdown products ADP and adenosine can act as extracellular messengers in a range of biological processes. Extracellular adenine nucleotides are metabolized by a number of enzymes including NTPDases and 5'-nucleotidase, which are considered to be the major regulators of purinergic signaling in the blood. Previous work by our group demonstrated that ATPase and ADPase activities in rat serum exhibit a 24-h temporal pattern, with higher enzyme activity during the dark (activity) phase. It was found that stress can cause disruptions in biological circadian rhythms and in the cardiovascular system. Therefore, the aim of the present study was to examine the influence of acute stress exposure upon temporal patterns of NTPDase and 5-nucleotidase enzyme activities in rat blood serum., Methods: Adult male Wistar rats were divided into 4 groups: ZT0, ZT6, ZT12 and ZT18. Each group was subdivided in 4 groups: control, immediately, 6 h and 24 h after one hour of restraint stress. ATP, ADP and AMP hydrolysis were assayed in the serum., Results: All stressed groups showed significant decreases in all enzyme activities at ZT 12 and ZT 18 when compared with control., Conclusion: Acute stress provokes a decrease in nucleotidase activities dependent on the time that this stress occurs and this effect appears to persist for at least 24 hours. Stress can change levels of nucleotides, related to increased frequency of cardiovascular events during the activity phase. Altered levels of nucleotides in serum may be involved in cardiovascular events more frequent during the activity phase in mammals, and with their etiology linked to stress.

Objectives: This study established the value of the 6‐sulfatoxymelatonin (aMT6s) urine concentration as a predictor of the therapeutic response to noradrenaline reuptake inhibitors in depressive patients., Methods: Twenty-two women aged 18-60 years were selected. Depressive symptoms were assessed by using the Hamilton Depression Scale. Urine samples were collected at 0600-1200 h, 1200-1800 h, 1800-2400 h, and 2400-0600 h intervals, 1 day before and 1 day after starting on the nortriptyline treatment. Urine aMT6s concentration was analyzed by a one-way analysis of variance/Bonferroni test. Spearman's rank correlation coefficient was used to analyze the correlation between depressive symptoms after 2 weeks of antidepressant treatment and the increase in aMT6s urine concentration., Results: Higher and lower size effect groups were compared by independent Student's t-tests. At baseline, the 2400‐ to 0600‐h interval differed from all other intervals presenting a significantly higher aMT6s urine concentration. A significant difference in aMT6s urine concentrations was found 1 day after treatment in all four intervals. Higher size effect group had lower levels of depressive symptoms 2 weeks after the treatment. A positive correlation between depressive symptoms and the delta of aMT6s in the 2400-0600 h interval was observed., Conclusion: Our results reinforce the hypothesis that aMT6s excretion is a predictor of clinical outcome in depression, especially in regard to noradrenaline reuptake inhibitors.

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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Morningness-eveningness dimension in humans have been indicated to influence social behavior and individual health. The aim of the present study was to investigate the association of the morningness-eveningness dimension with behavioral and health aspects in a sample of undergraduate students. We assessed demographic data; the Pittsburgh Sleep Quality Index was used to evaluate sleep quality; the Morningness/Eveningness Questionnaire to determine morningness-eveningness, and the Self-Reporting Questionnaire to assess minor psychiatric disorders. A total of 372 students (66.7% females), on average 21.6 years old, participated in this study. Among them, 92.2% did not smoke, 58.9% engaged in physical activities, and 19.7% were night-shift workers. In regard to morningness-eveningness, 55.9% of the participants were intermediate between evening (39.5%) and morning (4.6%) types. Poor sleep quality (OR = 1.89), minor psychiatric disorders (OR = 1.92), and tobacco consumption (OR = 3.65) predominated among evening types. Evening types were predominantly males (OR = 1.72). This study suggests that evening types are more vulnerable to sleep and psychiatric disturbances, and tend to smoke more than morning types.

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 7 days 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 5 min (phase I) and from 15-30 min (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) 30 min 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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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.

Pain exhibits temporal variations in intensity due to multiple factors, including endogenous neuroendocrine and various external influences that vary over the 24 h. Also, medications can vary in potency and/or toxicity according to the time when they are administered. However, there is no consensus among studies regarding the 24-h pattern of analgesia during labor. Taking into account the time-of-day when labor analgesia is administered, this study aimed to answer two questions: (i) Is there diurnal variation in visual analogue scale (VAS)-rated pain relief and duration of intrathecal analgesia in patients undergoing labor analgesia? (ii) If there is, what is the influence of the duration of labor on the diurnal variation of the level of pain relief and duration of intrathecal analgesia? This prospective cohort included 41 healthy, nulliparous women in the first stage of labor undergoing spinal-epidural (CSE) analgesia using fentanyl combined with bupivacaine. Subjects had an epidural catheter fitted for additional, patient-controlled analgesia (PCA) if their pain relief was unsatisfactory. The number of VAS assessments (n = 558) was divided into six time periods of the 24 h. The adjusted coefficient of determination (r(2)), the proportion of the variance explained by the association between the duration of labor and the temporal pattern of the outcomes variable, was 58% (r(2) = 0.58) for pain relief and 44% (r(2) = 0.44) for duration of intrathecal analgesia. The peak effect of labor analgesia occurred between 02:00 and 05:59 h. However, the duration of intrathecal analgesia showed two peaks, i.e., at approximately 00:00 and approximately 12:00 h. These results demonstrate that labor analgesia achieved by fentanyl combined with bupivacaine shows a diurnal pattern in pain relief and duration of spinal analgesia. However, part of these temporal patterns was explained by the association with duration of labor.

Objective: This study evaluates the State-Trait Anxiety Inventory (STAI) structure using a Rasch psychometric approach, and a refined and shorter STAI version is proposed., Methods: A cross-sectional study was performed with 900 inpatients scheduled for elective surgery. Age varied from 18 to 60 years (American Society of Anesthesiologists physical status I-III). Demographic information was collected using a structured questionnaire. The measuring instrument (the STAI) was applied to all patients in the afternoon before the surgery and prior to the patients receiving preoperative sedatives., Results: Rasch analysis of the state and trait anxiety scales was performed separately. This analysis demonstrated that the original format of state and trait scales fails to show invariance across the trait-state anxiety level, which results in the unstable performance of items. The refined scale was retested in two subsequent random samples of 300 subjects each, and the results were confirmed. The performance was adequate regardless of gender. In the analysis, some items of the state scale (items 3,4,9,10,12,15, and 20) were deleted due to poor fit statistics. The remaining 13 items showed unidimensionality, local independence, and adequate index of internal consistency. Also, the original trait scale displayed several weaknesses. First, the four-point Likert response scale proved to be inadequate, and threshold disorders were found in all 20 items. Also, the original trait scale showed insufficient item-trait interaction and several individual item misfits. Following the rescoring process, and retesting in a second random sample, items were excluded (namely Items 3, 4, 11, 13, 14, 15, 18, and 19). The refined version showed local independence, unidimensionality, and adequate fit statistics., Discussion: The results indicate that the application of the Rasch model led to the refinement of the classic STAI state and trait scales. In addition, they suggest that these shorter versions have a more suitable psychometric performance and are free of threshold disorders and differential item functioning problems., (Published by Elsevier Inc.)

Aim: The endogenous circadian clock generates daily variations of physiological and behavior functions such as the endogenous interindividual component (morningness/eveningness preferences). Also, mood disorders are associated with a breakdown in the organization of ultradian rhythm. Therefore, the purpose of the present study was to assessed the association between chronotype and the level of depressive symptoms in a healthy sample population. Furthermore, the components of the depression scale that best discriminate the chronotypes were determined., Methods: This cross-sectional study involved 200 volunteers, aged 18-99 years, 118 women and 82 men. The instruments were the Montgomery-Asberg Depression Rating Scale (MADRS), the Morningness/Eveningness Questionnaire, the Self-Reporting Questionnaire-20, and the future self-perception questionnaire., Results: Logistic regression showed that subjects with the eveningness chronotype had a higher chance of reporting more severe depressive symptoms compared to morning- and intermediate-chronotypes, with an odds ratio (OR) of 2.83 and 5.01, respectively. Other independent cofactors associated with a higher level of depressive symptoms were female gender (OR, 3.36), minor psychiatric disorders (OR, 3.70) and low future self-perception (OR, 3.11). Younger age, however, was associated with a lower level of depressive symptoms (OR, 0.97). The questions in the MADRS that presented higher discriminate coefficients among chronotypes were those related to sadness, inner tension, sleep reduction and pessimism., Conclusion: Identification of an association between evening typology and depressive symptoms in healthy samples may be useful in further investigation of circadian typology and the course of depressive disease.

Melatonin is a hormone primarily synthesized by the pineal gland and has been shown to govern seasonal and circadian rhythms, as well as the immune system, certain behaviours, and responses to stress. Chronic exposure to stress is involved in the etiology of human depression, and depressed patients present changes in circadian and seasonal rhythms. This study investigated the effects of daily exogenous melatonin (1 and 10 mg/kg, p.o.) and imipramine (20 mg/kg, i.p.) on the changes in the coat state, grooming behaviour and corticosterone levels induced by the unpredictable chronic mild stress model of depression in mice. As expected, the 5 weeks of unpredictable chronic mild stress schedule induced significant degradation of the coat state, decreased grooming and increased serum corticosterone levels. All of these unpredictable chronic mild stress-induced changes were counteracted by melatonin (P<0.05) and imipramine (P<0.01). Especially in view of the relevance of stress as a major contributing factor in depression, as well as the alleged importance of normalizing a hyperfunctioning HPA axis and resynchronizing circadian rhythms for a successful treatment of depression, this study reassesses the potential of melatonin as an antidepressant.

Unlabelled: Recent evidence has demonstrated analgesic, anti-inflammatory, and anxiolytic properties of melatonin. Taking into account that higher anxiety makes the control of postoperative pain more difficult, one can hypothesize that melatonin anxiolytic and analgesic effects improve the control of postoperative pain. Thus, we conducted a randomized, double-blind, placebo-controlled study with 59 patients undergoing abdominal hysterectomy to test the hypothesis that melatonin is as effective as clonidine and that both are more effective than placebo in reducing postoperative pain. Additionally, we compared their anxiolytic effects on postoperative pain. Patients were randomly assigned to receive oral melatonin (5 mg) (n = 20), clonidine (100 microg) (n = 19), or placebo (n = 20) orally. In addition to primary outcomes of pain intensity and analgesic consumption, secondary outcome measures included postoperative state anxiety. In anxious patients 6 hours after surgery, the number of patients needed to be to prevent moderate to intense pain during the first 24 hours after surgery was 1.52 (95% CI, 1.14 to 6.02) and 1.64 (95% CI, 1.29 to 5.93), respectively, in the melatonin and clonidine groups compared with placebo. Also, the anxiolytic effect of melatonin and clonidine resulted in reduced postoperative morphine consumption by more than 30%. However, in the mildly anxious, it was not observed the treatment effect on pain., Perspectives: The preoperative anxiolysis with melatonin or clonidine reduced postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy. The effects these 2 drugs were equivalent and greater than with placebo.

Background: An increased anxiety may be associated with a higher risk of surgical site infection (SSI), but there is little objective data on the effect of preoperative anxiolytic interventions on SSI. To address this issue, we evaluated the effects of preoperative diazepam on postoperative SSI following abdominal hysterectomy., Methods: This randomized, double-blinded, placebo-controlled study included 130 patients, American Society of Anesthesiologist physical status 1 or 2. Patients were randomly assigned to receive either oral diazepam 10 mg (n = 65) or placebo (n = 65) the night before and 1 hour prior to surgery. The assessment instruments were the Visual Analogue Scale and the State-Trait Anxiety Inventory. SSI was diagnosed according to the criteria of the Centers for Disease Control and Prevention with standard follow-up of 30 days., Results: The relative risk (RR) was 1.79 (95% confidence interval [CI]: 1.31-2.43), and the number of patients that needed to be treated was 5.2 (95% CI: 2.74-50.76) to prevent 1 additional SSI. The RR for SSI in placebo-treated patients with high postoperative anxiety was 1.65 (95% CI: 1.07-2.56)., Conclusion: Diazepam-treated patients showed lower postoperative anxiety and lower incidence of SSI up to 30 days after surgery compared with placebo in patients undergoing abdominal hysterectomy.

The goal of this study was to translate and adapt the Night Eating Questionnaire to Portuguese and assess the reliability of the Portuguese-language version. The study included two phases. The first consisted of: (1) translation into Portuguese; (2) back-translation into English; (3) correction and semantic adaptation; (4) content validation; and (5) assessment of the understanding of the questionnaire by means of 10 cm Visual Analogue Scales with 30 adult users of a nutritional support clinic. In the second phase, the questionnaire's reliability was assessed in 100 subjects with similar demographic characteristics to the first sample. In the fifth step, understanding of the instrument assessed by the visual analogue scales was 8.20+/-1.55 cm. The instrument showed satisfactory internal consistency, with an overall Cronbach alpha of 0.78. The Portuguese version proved to be easily understandable, with good semantic validation and consistency, suggesting that the questionnaire may be a good instrument for screening the night eating syndrome. However, other psychometric characteristics of this instrument need to be assessed in samples with different social and educational levels.

Background: Propofol is an accepted method of sedation for an ERCP and generally achieves deep sedation rather than conscious sedation, and dexmedetomidine has sedative properties of equivalent efficacy., Objective: To examine the hypothesis that dexmedetomidine is as effective as propofol combined with fentanyl for providing conscious sedation during an ERCP., Design and Setting: Randomized, blind, double-dummy clinical trial., Patients: Twenty-six adults, American Society of Anesthesiologists status I to III, underwent an ERCP., Interventions: Patients were randomized to receive either propofol (n = 14) (target plasma concentration range 2-4 microg/mL) combined with fentanyl 1 microg/kg, or dexmedetomidine (n = 12) 1 microg/kg for 10 minutes, followed by 0.2 to 0.5 microg/kg/min. Additional sedatives were used if adequate sedation was not achieved at the maximum dose allowed., Main Outcomes Measurements: The sedation level was assessed by the Richmond alertness-sedation scale and the demand for additional sedatives. Furthermore, heart rate, blood pressure, oxygen saturation, and respiratory rate were continuously assessed., Results: The relative risk (RR) was 2.71 (95% CI, 1.31-5.61) and the number of patients that needed to be treated (NNT) was 1.85 (95% CI, 1.19-4.21) to observe one additional patient with drowsiness 15 minutes after sedation in the dexmedetomidine group. Also, the RR was 9.42 (95% CI, 1.41-62.80), and the NNT was 1.42 (95% CI, 1.0-2.29) to require additional analgesic. However, there was also a greater reduction in blood pressure, a lower heart rate, and greater sedation after the procedure., Conclusions: Dexmedetomidine alone was not as effective as propofol combined with fentanyl for providing conscious sedation during an ERCP. Furthermore, dexmedetomidine was associated with greater hemodynamic instability and a prolonged recovery.

Background: Melatonin has sedative, analgesic, antiinflammatory, antioxidative, and chronobiotic effects. We determined the impact of oral melatonin premedication on anxiolysis, analgesia, and the potency of the rest/activity circadian rhythm., Methods: This randomized, double-blind, placebo-controlled study included 33 patients, ASA physical status I-II, undergoing abdominal hysterectomy. Patients were randomly assigned to receive either oral melatonin 5 mg (n = 17) or placebo (n = 16) the night before and 1 h before surgery. The analysis instruments were the Visual Analog Scale, the State-Trait Anxiety Inventory, and the actigraphy., Results: The number of patients that needed to be treated to prevent one additional patient reporting high postoperative anxiety and moderate to intense pain in the first 24 postoperative hours was 2.53 (95% CI, 1.41-12.22) and 2.20 (95% CI, 1.26-8.58), respectively. The number-needed-to-treat was 3 (95% CI, 1.35-5.0) to prevent high postoperative anxiety in patients with moderate to intense pain, when compared with 7.5 (95% CI, 1.36-infinity) in the absence of pain or mild pain. Also, the treated patients required less morphine by patient-controlled analgesia, as assessed by repeated measures ANOVA (F[1,31] = 6.05, P = 0.02). The rest/activity cycle, assessed by actigraphy, showed that the rhythmicity percentual of 24 h was higher in the intervention group in the first week after discharge ([21.16 +/- 8.90] versus placebo [14.00 +/- 7.10]; [t = -2.41, P = 0.02])., Conclusions: This finding suggested that preoperative melatonin produced clinically relevant anxiolytic and analgesic effects, especially in the first 24 postoperative hours. Also, it improved the recovery of the potency of the rest/activity circadian rhythm.

We assessed the effect of small clonidine doses on anxiolysis, analgesia, and hemodynamic stability in patients undergoing abdominal hysterectomy. A total of 61 patients, ASA status I-II, were randomly assigned to receive either oral clonidine 100 microg (n = 29) or placebo (n = 32) before surgery and 24 h after surgery. The use of clonidine resulted in anxiolysis and analgesia throughout the 72 h after surgery, although the subjects who received clonidine were sleepier than the control group for the first 6 h after surgery. The number needed to treat was 3 (95% confidence interval [CI], 1.72-9.42) to prevent intense anxiety in patients with moderate to intense postoperative pain, compared with 40 (95% CI, 18.79-99.68) in the absence of pain or with mild pain. In the treated patients, 68% had an average heart rate less than 70 bpm during surgery, compared with 21.40% in the placebo group (number needed to treat, 2; 95% CI, 1.29-2.80). The clonidine patients required small ropivacaine doses during the surgery but not less morphine by patient-controlled analgesia. A clinically relevant anxiolytic effect was found in patients who received oral clonidine in the perioperative period, and this suggests that clonidine might be a useful therapeutic alternative to other preoperative sedatives.