Cortico-limbic pain mechanisms Thompson, Jeremy M.; Neugebauer, Volker
Neuroscience letters,
05/2019, Letnik:
702
Journal Article
Recenzirano
Odprti dostop
Pain has a strong emotional component and is defined by its unpleasantness. Chronic pain represents a complex disorder with anxio-depressive symptoms and cognitive deficits. Underlying mechanisms are ...still not well understood but an important role for interactions between prefrontal cortical areas and subcortical limbic structures has emerged. Evidence from preclinical studies in the rodent brain suggests that neuroplastic changes in prefrontal (anterior cingulate, prelimbic and infralimbic) cortical and subcortical (amygdala and nucleus accumbens) brain areas and their interactions (corticolimbic circuitry) contribute to the complexity and persistence of pain and may be predetermining factors as has been proposed in recent human neuroimaging studies.
Amygdala Plasticity and Pain Thompson, Jeremy M.; Neugebauer, Volker
Pain research & management,
01/2017, Letnik:
2017
Journal Article
Recenzirano
Odprti dostop
The amygdala is a limbic brain region that plays a key role in emotional processing, neuropsychiatric disorders, and the emotional-affective dimension of pain. Preclinical and clinical studies have ...identified amygdala hyperactivity as well as impairment of cortical control mechanisms in pain states. Hyperactivity of basolateral amygdala (BLA) neurons generates enhanced feedforward inhibition and deactivation of the medial prefrontal cortex (mPFC), resulting in pain-related cognitive deficits. The mPFC sends excitatory projections to GABAergic neurons in the intercalated cell mass (ITC) in the amygdala, which project to the laterocapsular division of the central nucleus of the amygdala (CeLC; output nucleus) and serve gating functions for amygdala output. Impairment of these cortical control mechanisms allows the development of amygdala pain plasticity. Mechanisms of abnormal amygdala activity in pain with particular focus on loss of cortical control mechanisms as well as new strategies to correct pain-related amygdala dysfunction will be discussed in the present review.
This report presents the Consolidated Standards of Reporting Trials (CONSORT) extension for the stepped wedge cluster randomised trial (SW-CRT). The SW-CRT involves randomisation of clusters to ...different sequences that dictate the order (or timing) at which each cluster will switch to the intervention condition. The statement was developed to allow for the unique characteristics of this increasingly used study design. The guideline was developed using a Delphi survey and consensus meeting; and is informed by the CONSORT statements for individual and cluster randomised trials. Reporting items along with explanations and examples are provided. We include a glossary of terms, and explore the key properties of the SW-CRT which require special consideration in their reporting.
Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage
.... Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity
. In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli.
Abstract Introduction Endogenous dentin matrix metalloproteinases (MMPs) contribute to extracellular collagen matrix degradation in hybrid layers after adhesive dentin bonding procedures. Endodontic ...irrigants, including chlorhexidine and ethylenediaminetetraacetic acid (EDTA), might help protect the hybrid layer from this process. The objective of the present study was to determine the exposure time necessary for EDTA to inactivate endogenous MMP activity in human dentin. Methods Dentin beams (2 × 1 × 3 mm) were prepared from mid-coronal dentin of extracted third molars. The beams were demineralized in 10 wt% phosphoric acid, which also activated endogenous MMPs, and were divided into 4 experimental groups on the basis of exposure time to 17% EDTA (0, 1, 2, or 5 minutes). A generic colorimetric MMP assay measured MMP activity via absorbance at 412 nm. Data were evaluated by Kruskal-Wallis analysis of variance, followed by Dunn pair-wise comparisons at α = 0.05. Results All exposure times resulted in significant inhibition ( P < .001) compared with unexposed controls. Specifically, percent inhibition for 1-, 2-, and 5-minute exposure times was 55.1% ± 21.5%, 72.8% ± 11.7%, and 74.7% ± 19.7%, respectively. Conclusions Seventeen percent EDTA significantly inhibits endogenous MMP activity of human dentin within 1–2 minutes. This might minimize hybrid layer degradation after resin bonding procedures in the root canal space.
The weighted ensemble (WE) family of methods is one of several statistical mechanics-based path sampling strategies that can provide estimates of key observables (rate constants and pathways) using a ...fraction of the time required by direct simulation methods such as molecular dynamics or discrete-state stochastic algorithms. WE methods oversee numerous parallel trajectories using intermittent overhead operations at fixed time intervals, enabling facile interoperability with any dynamics engine. Here, we report on the major upgrades to the WESTPA software package, an open-source, high-performance framework that implements both basic and recently developed WE methods. These upgrades offer substantial improvements over traditional WE methods. The key features of the new WESTPA 2.0 software enhance the efficiency and ease of use: an adaptive binning scheme for more efficient surmounting of large free energy barriers, streamlined handling of large simulation data sets, exponentially improved analysis of kinetics, and developer-friendly tools for creating new WE methods, including a Python API and resampler module for implementing both binned and "binless" WE strategies.
Promoting the uptake of vaccination for infectious diseases such as COVID-19 remains a global challenge, necessitating collaborative efforts between public health units (PHUs) and communities. ...Applied behavioural science can play a crucial role in supporting PHUs' response by providing insights into human behaviour and informing tailored strategies to enhance vaccination uptake. Community engagement can help broaden the reach of behavioural science research by involving a more diverse range of populations and ensuring that strategies better represent the needs of specific communities. We developed and applied an approach to conducting community-based behavioural science research with ethnically and socioeconomically diverse populations to guide PHUs in tailoring their strategies to promote COVID-19 vaccination. This paper presents the community engagement methodology and the lessons learned in applying the methodology.
The community engagement methodology was developed based on integrated knowledge translation (iKT) and community-based participatory research (CBPR) principles. The study involved collaboration with PHUs and local communities in Ontario, Canada to identify priority groups for COVID-19 vaccination, understand factors influencing vaccine uptake and co-design strategies tailored to each community to promote vaccination. Community engagement was conducted across three large urban regions with individuals from Eastern European communities, African, Black, and Caribbean communities and low socioeconomic neighbourhoods.
We developed and applied a seven-step methodology for conducting community-based behavioural science research: (1) aligning goals with system-level partners; (2) engaging with PHUs to understand priorities; (3) understanding community strengths and dynamics; (4) building relationships with each community; (5) establishing partnerships (community advisory groups); (6) involving community members in the research process; and (7) feeding back and interpreting research findings. Research partnerships were successfully established with members of prioritized communities, enabling recruitment of participants for theory-informed behavioural science interviews, interpretation of findings, and co-design of targeted recommendations for each PHU to improve COVID-19 vaccination uptake. Lessons learned include the importance of cultural sensitivity and awareness of sociopolitical context in tailoring community engagement, being agile to address the diverse and evolving priorities of PHUs, and building trust to achieve effective community engagement.
Effective community engagement in behavioural science research can lead to more inclusive and representative research. The community engagement approach developed and applied in this study acknowledges the diversity of communities, recognizes the central role of PHUs, and can help in addressing complex public health challenges.
Chronic neuropathic pain is an important healthcare issue with significant emotional components. The amygdala is a brain region involved in pain and emotional-affective states and disorders. The ...central amygdala output nucleus (CeA) contains small-conductance calcium-activated potassium (SK) channels that can control neuronal activity. A clinically available therapeutic, riluzole can activate SK channels and may have antinociceptive effects through a supraspinal action. We tested the hypothesis that riluzole inhibits neuropathic pain behaviors by inhibiting pain-related changes in CeA neurons, in part at least through SK channel activation.
Brain slice physiology and behavioral assays were done in adult Sprague Dawley rats. Audible and ultrasonic vocalizations and von Frey thresholds were measured in sham and neuropathic rats 4 weeks after left L5 spinal nerve ligation (SNL model). Whole cell patch-clamp recordings of regular firing CeA neurons in brain slices were used to measure synaptic transmission and neuronal excitability.
In brain slices, riluzole increased the SK channel-mediated afterhyperpolarization and synaptic inhibition, but inhibited neuronal excitability through an SK channel independent action. SNL rats had increased vocalizations and decreased withdrawal thresholds compared to sham rats, and intra-CeA administration of riluzole inhibited vocalizations and depression-like behaviors but did not affect withdrawal thresholds. Systemic riluzole administration also inhibited these changes, demonstrating the clinical utility of this strategy. SK channel blockade in the CeA attenuated the inhibitory effects of systemic riluzole on vocalizations, confirming SK channel involvement in these effects.
The results suggest that riluzole has beneficial effects on neuropathic pain behaviors through SK channel dependent and independent mechanisms in the amygdala.
•Riluzole, a clinically available therapeutic, inhibits averse affective neuropathic pain behaviors.•Behavioral effects of riluzole are blocked by potassium (SK) channel blockade in the amygdala.•Riluzole increases SK-channel dependent medium afterhyperpolarization (mAHP) of amygdala neurons.•Riluzole increases synaptic inhibition in amygdala brain slices in an SK channel-dependent manner.•Inhibitory effects of riluzole on excitability of amygdala neurons are SK-channel independent.
Daily activity timing in the Anthropocene Gilbert, Neil A.; McGinn, Kate A.; Nunes, Laura A. ...
Trends in ecology & evolution (Amsterdam),
April 2023, 2023-04-00, 20230401, Letnik:
38, Številka:
4
Journal Article
Recenzirano
Animals are facing novel ‘timescapes’ in which the stimuli entraining their daily activity patterns no longer match historical conditions due to anthropogenic disturbance. However, the ecological ...effects (e.g., altered physiology, species interactions) of novel activity timing are virtually unknown. We reviewed 1328 studies and found relatively few focusing on anthropogenic effects on activity timing. We suggest three hypotheses to stimulate future research: (i) activity-timing mismatches determine ecological effects, (ii) duration and timing of timescape modification influence effects, and (iii) consequences of altered activity timing vary biogeographically due to broad-scale variation in factors compressing timescapes. The continued growth of sampling technologies promises to facilitate the study of the consequences of altered activity timing, with emerging applications for biodiversity conservation.
Recent years have seen a growing interest in the role of time in structuring biological patterns and processes.Among nature’s most dramatic and universal temporal patterns are the daily activity patterns shown by organisms. Although the endogenous mechanisms (e.g., circadian rhythms) giving rise to such patterns have been researched extensively, ecological aspects of daily activity patterns are now receiving greater attention.Plasticity in daily activity patterns may represent an in situ adaptation to human-mediated stressors such as climate change and urbanization. However, the effects of novel activity timing, which may emerge at multiple levels of biological organization, are poorly understood.We offer hypotheses to catalyze future research on the ecological consequences of altered daily activity timing and discuss approaches that may facilitate such investigations.
Understanding the density‐dependent processes that drive population demography in a changing world is critical in ecology, yet measuring performance–density relationships in long‐lived mammalian ...species demands long‐term data, limiting scientists' ability to observe such mechanisms. We tested performance–density relationships for an opportunistic omnivore, grizzly bears (Ursus arctos, Linnaeus, 1758) in the Greater Yellowstone Ecosystem, with estimates of body composition (lean body mass and percent body fat) serving as indicators of individual performance over two decades (2000–2020) during which time pronounced environmental changes have occurred. Several high‐calorie foods for grizzly bears have mostly declined in recent decades (e.g., whitebark pine Pinus albicaulis, Engelm, 1863), while increasing human impacts from recreation, development, and long‐term shifts in temperatures and precipitation are altering the ecosystem. We hypothesized that individual lean body mass declines as population density increases (H1), and that this effect would be more pronounced among growing individuals (H2). We also hypothesized that omnivory helps grizzly bears buffer energy intake from changing foods, with body fat levels being independent from population density and environmental changes (H3). Our analyses showed that individual lean body mass was negatively related to population density, particularly among growing‐age females, supporting H1 and partially H2. In contrast, population density or sex had little effect on body fat levels and rate of accumulation, indicating that sufficient food resources were available on the landscape to accommodate successful use of shifting food sources, supporting H3. Our results offer important insights into ecological feedback mechanisms driving individual performances within a population undergoing demographic and ecosystem‐level changes. However, synergistic effects of continued climate change and increased human impacts could lead to more extreme changes in food availability and affect observed population resilience mechanisms. Our findings underscore the importance of long‐term studies in protected areas when investigating complex ecological relationships in an increasingly anthropogenic world.
Revealing mechanisms underlying demography of long‐lived omnivores is of critical in a changing world. Using long‐term data on grizzly bears from the Greater Yellowstone Ecosystem, we show that variation in individual performance (measured as lean body mass) is primarily a density‐dependent process, particularly among younger females. Conversely, large omnivores exhibit plastic tactics in the face of current landscape‐level perturbations maintaining seasonal threshold of body fat required for hibernation and reproduction. However, synergistic effects of continued climate change and other forms of human impact could in the future affect food availability, and consequently, the observed population resilience mechanisms.
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