Efeitos do tramadol no modelo de dor induzida por obstrução intestinal em eqüinos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relationship between pain and anxiety in rats

Clinically, it is well known that neuropathic pain often induces comorbid symptoms such as anxiety. In turn, also anxiety has been associated with a heightened experience of pain. Although, the link between pain and anxiety is well recognized in humans, the neurobiological basis of this relationship remains unclear. Therefore, the aim of the current study was to investigate the influence of neuropathic pain on anxiety and vice versa in rats by assessing not only pain-related behaviour but also by discovering possible key substrates which are responsible for the interrelation of pain and anxiety.rnIn rats with a chronic constriction of the sciatic nerve (CCI model) anxiety-like behaviour was observed. Since anxiety behaviour could be completely abolished after the treatment of the pure analgesic drugs gabapentin and morphine, we concluded that anxiety was caused by the strong persistent pain. Furthermore, we found that the neuropeptides oxytocin and vasopressin were upregulated in the amygdala of CCI rats, and the intra-amygdala treatment of an oxytocin antagonist but not the vasopressin antagonist could reduce anxiety-like behaviour in these animals, while no effect on mechanical hypersensitivity was observed. These data indicate that oxytocin is implicated in the underlying neuronal processes of pain-induced anxiety and helps to elucidate the pathophysiological mechanisms of neuropathic pain. rnTo assess the influence of trait anxiety on pain sensation in rats, we determined mechanical hypersensitivity after sciatic nerve lesion (CCI) in animals selectively bred for high anxiety or low anxiety behaviour. The paw withdrawal thresholds were significantly decreased in high anxiety animals in comparison to low anxiety animals 2 and 3 weeks after surgery. In a second model state anxiety was induced by the sub-chronic injection of the anxiogenic drug pentylentetrazol in naive rats. Pain response to mechanical stimuli was increased after pharmacologically-induced anxiety. These results provided evidence for the influence of both trait and state anxiety on pain sensation. rnThe studies contribute to the elucidation of the relationship between pain and anxiety. We investigated that the neuropathic pain model displays sensory as well as emotional factors of peripheral neuropathy. Changes in expression levels of neuropeptides in the central nervous system due to neuropathic pain may contribute to the pathophysiology of neuropathic pain and its related symptoms in animals which might also be relevant for human scenarios. The results of the current study also confirm that anxiety plays an important role in the perception of pain. rnA better understanding of pain behaviour in animals might improve the preclinical profiling of analgesic drugs during development. The study highlights the potential use of the rat model as a new preclinical tool to further investigate the link between pain and anxiety by determining not only the sensory reflexes after painful stimuli but also the more complex pain-related behaviour such as anxiety.rn

Dopaminergic modulation of the human reward system: a placebo-controlled dopamine depletion fMRI study

Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity in 10 healthy volunteers. In addition to blood-oxygen-level-dependent (BOLD) contrast we assessed the effect of dopaminergic depletion on prolactin response, peripheral markers for dopamine and norepinephrine. In the placebo condition we found increased activation in the left caudate and left cingulate gyrus during anticipation of reward. In the α-methylparatyrosine condition there was no significant brain activation during anticipation of reward or loss. In α-methylparatyrosine, anticipation of reward vs. loss increased activation in the right insula, left frontal, right parietal cortices and right cingulate gyrus. Comparing placebo versus α-methylparatyrosine showed increased activation in the left cingulate gyrus during anticipation of reward and the left medial frontal gyrus during anticipation of loss. α-methylparatyrosine reduced levels of dopamine in urine and homovanillic acid in plasma and increased prolactin. No significant effect of α-methylparatyrosine was found on norepinephrine markers. Our findings implicate distinct patterns of BOLD underlying reward processing following dopamine depletion, suggesting a role of dopaminergic neurotransmission for anticipation of monetary reward.

Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring

Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P <0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P <0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P <0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P <0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P <0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome. © Journal compilation © 2008 The Physiological Society.

Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development.

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders.

Community perceptions of orangutan conservation and palm oil in Melbourne, Australia

This study examined Greater Melbourne residents’ perspectives toward orangutan conservation through a mixed mode survey method, using postal surveys (N = 108, response rate = 11.8%) and telephone interviews (N = 50, response rate = 51%). Differences were found between knowledge levels about orangutans, attitudes towards orangutans and behavioural intentions. It appears probable that when an individual is educated about how human beings impact orangutans and holds positive attitudes towards them, most would try to reduce their impact.

A revised Australian dietary guideline index and its association with key sociodemographic factors, health behaviors and body mass index in peri-retirement aged adults

The Dietary Guideline Index, a measure of diet quality, was updated to reflect the 2013 Australian Dietary Guidelines. This paper describes the revision of the index (DGI-2013) and examines its use in older adults. The DGI-2013 consists of 13 components reflecting food-based daily intake recommendations of the Australian Dietary Guidelines. In this cross-sectional study, the DGI-2013 score was calculated using dietary data collected via an 111-item food frequency questionnaire and additional food-related behaviour questions. The DGI-2013 score was examined in Australian adults (aged 55-65 years; n = 1667 men; 1801 women) according to sociodemographics, health-related behaviours and BMI. Women scored higher than men on the total DGI-2013 and all components except for dairy. Those who were from a rural area (men only), working full-time (men only), with lower education, smoked, did not meet physical activity guidelines, and who had a higher BMI, scored lower on the DGI-2013, highlighting a group of older adults at risk of poor health. The DGI-2013 is a tool for assessing compliance with the Australian Dietary Guidelines. We demonstrated associations between diet quality and a range of participant characteristics, consistent with previous literature. This suggests that the DGI-2013 continues to demonstrate convergent validity, consistent with the original Dietary Guideline Index.

Next steps in the logic of consumer-led self-management : translating chronic condition self-management programmes (CCSM) into lifestyle management programmes for young people

The techniques applied in chronic condition self-management programmes (CCSM) to support patients with chronic conditions are basic counselling and communication strategies that would benefit people at all stages of life and wellness. The question being explored here is why, as a society, we wait until people develop essentially preventable chronic conditions before helping them to develop the life skills they need to manage their lives and their human interactions better rather than working to avoid or prevent many chronic conditions that develop as a result of people lacking such skills? If we were to teach coping and managing skills to everyone in a supportive and structured way, using the peer-led teaching and learning strategies and basic counselling and education processes that have been shown to be successful for other older groups with chronic illness, the overall population impact would be more significant. Therefore why wait until people have chronic conditions before empowering them with basic life management techniques? Do people need to be sick before they can be motivated to live more effective lives? Is sickness the main stimulus for triggering health-related behaviour change or can other factors in people’s lives serve to inform and motivate lifestyle change?

Translating chronic condition self-management programmes (CCSM) into lifestyle management programmes for young people

The techniques applied in chronic condition self-management programmes (CCSM) to support patients with chronic conditions are basic counselling and communication strategies that would benefit people at all stages of life and wellness. The question being explored here is why, as a society, we wait until people develop essentially preventable chronic conditions before helping them to develop the life skills they need to manage their lives and their human interactions better rather than working to avoid or prevent many chronic conditions that develop as a result of people lacking such skills? If we were to teach coping and managing skills to everyone in a supportive and structured way, using the peer-led teaching and learning strategies and basic counselling and education processes that have been shown to be successful for other older groups with chronic illness, the overall population impact would be more significant. Therefore why wait until people have chronic conditions before empowering them with basic life management techniques? Do people need to be sick before they can be motivated to live more effective lives? Is sickness the main stimulus for triggering health-related behaviour change or can other factors in people's lives serve to inform and motivate lifestyle change.

Have adults lost their sense of play? An observational study of the social dynamics of physical (in)activity in German and Hawaiian leisure settings

BACKGROUND: Physical inactivity is one of the biggest health problems nowadays. Recent research shows that socio-cultural barriers to physical activity are mostly related to modern lifestyles. However, there is a lack of research on how social and group dynamics influence engagement in physical activity. Furthermore, there are few cross-cultural studies that have compared the social dynamics of (in)activity in different cultural settings. This paper therefore aims to analyse how social group dynamics influence physical activity and inactivity in informal social environments and whether physical activity is influenced by the socio-cultural settings. METHODS: The paper presents the qualitative data collected within a covert participant observation study. Data was collected by keeping observational notes in order to record typical, regular patterns regarding physical (in)activity related behaviour of groups at an artificial open air swimming pool in Germany and a natural pond in Hawai'i. The data collection period was eight and a half months. Data was interpreted based on constant comparative analysis in order to identify most generative patterns in the field notes. RESULTS: Group structures appear to play a significant role regarding the activity of the group members. In this study, we identified four key factors that influence group based physical activity: 1) Physical activity seems to be a group disturbing behaviour particularly in larger groups of adults; 2) Physical activity appears to be more functional and less joyful in adults than in children; 3) Group activity is influenced by (in)activity anchors, including 'domestication' of a group's site, obesity, and controlling parents. 4) Physical activity is to a certain extent socially contagious, particularly with regard to playful activities. CONCLUSIONS: Successful promotion of physical activity should target the social structures of inactive individuals' groups. In this regard, one of the main problems is that fun and wellbeing, as very important targets of public health strategies for the adult population, appear not to be compatible with physical activity. Developing strategies to reframe physical activity rather as 'fun' and less as functional may be one way to engage inactive individuals in physical activity in leisure settings.

From the workplace to the classroom:examining the impact of self-leadership learning strategies on higher educational attainment and success

Self-leadership is a concept from the organisational and management literature broadly combining processes of self-goal setting, self-regulation and self-motivation. Research has typically focused on the impact of self-leadership on work performance outcomes, with little attention to potential benefits for learning and development. In this paper, we employ a longitudinal design to examine the association of a number of processes of self-leadership with higher educational attainment in a sample of business students (N = 150). Self-reported use of strategies related to behavioural, cognitive and motivational aspects of self-leadership were measured in the first semester of the academic year, and correlated with end-of year grade point average. We found that in particular, self-goal setting, pro-active goal-related behaviour, behaviour regulation and direction, motivational awareness, and optimism were all significant predictors of educational attainment. We discuss implications for educational research and for teachers and tutors in practice.

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

Background: Preclinical studies have identified certain probiotics as psychobiotics a live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers. Objectives: To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants. An 8 week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT). Results: There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels. Conclusions: L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required.

Transition, school, friends and obesity risk models (the TranSFORM study)

The TranSFORM study demonstrated the impact that a change of school environment has on physical activity, sedentary and dietary behaviour in late childhood. Results provide strong evidence of the influence of friendship networks, and the potential for changing and reinforcing positive weight related behaviour in early adolescence.

Adolescent protective behaviour to reduce drug and alcohol use, alcohol-related harm and interpersonal violence

Typically adolescents' friends are considered a risk factor for adolescent engagement in risk-taking. This study took a more novel approach, by examining adolescent friendship as a protective factor. In particular it investigated friends' potential to intervene to reduce risk-taking. 540 adolescents (mean age 13.47 years) were asked about their intention to intervene to reduce friends' alcohol, drug and alcohol-related harms and about psychosocial factors potentially associated with intervening. More than half indicated that they would intervene in friends' alcohol, drug use, alcohol-related harms and interpersonal violence. Intervening was associated with being female, having friends engage in overall less risk-taking and having greater school connectedness. The findings provide an important understanding of increasing adolescent protective behavior as a potential strategy to reduce alcohol and drug related harms.

The role of personality in predicting hooning-related driving behaviour

‘Hooning’ constitutes a set of illegal and high-risk vehicle related activities typically performed by males aged 17-25, a group that is over-represented in road trauma statistics. This study used an online survey of 422 participants to test the efficacy of the Five Factor Model of Personality in predicting ‘loss of traction’ (LOT) hooning behaviour. Drivers who engaged in LOT behaviour scored significantly lower on the factor of Agreeableness than those who did not. Regression analyses indicated that the Five Factor Model of Personality was a significant predictor of LOT behaviour over and above sex and age, although Agreeableness was the only significant personality factor in the model. The findings may be used to better understand those drivers likely to engage in LOT behaviours. Road safety advertising and educational campaigns can target less socially agreeable drivers, and aim to encourage more agreeable attitudes to driving, particularly for younger male drivers.