Neuropeptide Y is up-regulated and induces antinociception in cancer-induced bone pain

Pain remains a major concern in patients suffering from metastatic cancer to the bone and more knowledge of the condition, as well as novel treatment avenues, are called for. Neuropeptide Y (NPY) is a highly conserved peptide that appears to play a central role in nociceptive signaling in inflammatory and neuropathic pain. However, little is known about the peptide in cancer-induced bone pain. Here, we evaluate the role of spinal NPY in the MRMT-1 rat model of cancer-induced bone pain. Our studies revealed an up-regulation of NPY-immunoreactivity in the dorsal horn of cancer-bearing rats 17 days after inoculation, which could be a compensatory antinociceptive response. Consistent with this interpretation, intrathecal administration of NPY to rats with cancer-induced bone pain caused a reduction in nociceptive behaviors that lasted up to 150 min. This effect was diminished by both Y1 (BIBO3304) and Y2 (BIIE0246) receptor antagonists, indicating that both receptors participate in mediating the antinociceptive effect of NPY. Y1 and Y2 receptor binding in the spinal cord was unchanged in the cancer state as compared to sham-operated rats, consistent with the notion that increased NPY results in a net antinociceptive effect in the MRMT-1 model. In conclusion, the data indicate that NPY is involved in the spinal nociceptive signaling of cancer-induced bone pain and could be a new therapeutic target for patients with this condition.Comment: 23 pages, 4 figure

Resistance Training Volume Enhances Muscle Hypertrophy but Not Strength in Trained Men

Purpose: The purpose of this study was to evaluate muscular adaptations between low-, moderate-, and high-volume resistance training protocols in resistance-trained men. Methods: Thirty-four healthy resistance-trained men were randomly assigned to one of three experimental groups: a low-volume group performing one set per exercise per training session (n = 11), a moderate-volume group performing three sets per exercise per training session (n = 12), or a high-volume group performing five sets per exercise per training session (n = 11). Training for all routines consisted of three weekly sessions performed on nonconsecutive days for 8 wk. Muscular strength was evaluated with one repetition maximum (RM) testing for the squat and bench press. Upper-body muscle endurance was evaluated using 50% of subjects bench press 1RM performed to momentary failure. Muscle hypertrophy was evaluated using B-mode ultrasonography for the elbow flexors, elbow extensors, mid-thigh, and lateral thigh. Results: Results showed significant preintervention to postintervention increases in strength and endurance in all groups, with no significant between-group differences. Alternatively, while all groups increased muscle size in most of the measured sites from preintervention to postintervention, significant increases favoring the higher-volume conditions were seen for the elbow flexors, mid-thigh, and lateral thigh. Conclusions: Marked increases in strength and endurance can be attained by resistance-trained individuals with just three 13-min weekly sessions over an 8-wk period, and these gains are similar to that achieved with a substantially greater time commitment. Alternatively, muscle hypertrophy follows a dose–response relationship, with increasingly greater gains achieved with higher training volumes. Ke

Espacios culturales y su relación con la comunidad local y sus públicos

El presente documento expone lo realizado en el proyecto de aplicación profesional Espacios culturales y su relación con la comunidad local y sus públicos del ITESO. En este proyecto se trabajó con el Instituto Cultural Cabañas (ICC) con el objetivo de lograr un acercamiento significativo entre el museo y los habitantes de los barrios vecinos, así como con la comunidad comercial del Mercado Libertad. Con la colaboración entre alumnos del ITESO, personal del ICC, personas del Mercado Libertad y el apoyo de investigadores y expertos en temas de cultura y desarrollo sociocultural, se buscó propiciar un vínculo entre el ICC y la comunidad inmediata mediante talleres de arte conceptual para los hijos de los comerciantes del Mercado Libertad. En este documento se muestran los resultados obtenidos, así como las propuestas y dificultades enfrentadas. Se plasma el planteamiento del proyecto, los resultados, el análisis, el contexto, observaciones, conclusiones y recomendaciones. En este proyecto trabajaron alumnos de las licenciaturas en Psicología, Mercadotecnia y Arquitectura

Espacios culturales y su relación con la comunidad local y sus públicos

El presente documento expone lo realizado en el proyecto de aplicación profesional Espacios culturales y su relación con la comunidad local y sus públicos del ITESO. En este proyecto se trabajó con el Instituto Cultural Cabañas (ICC) con el objetivo de lograr un acercamiento significativo entre el museo y los habitantes de los barrios vecinos, así como con la comunidad comercial del Mercado Libertad. Con la colaboración entre alumnos del ITESO, personal del ICC, personas del Mercado Libertad y el apoyo de investigadores y expertos en temas de cultura y desarrollo sociocultural, se buscó propiciar un vínculo entre el ICC y la comunidad inmediata mediante talleres de arte conceptual para los hijos de los comerciantes del Mercado Libertad. En este documento se muestran los resultados obtenidos, así como las propuestas y dificultades enfrentadas. Se plasma el planteamiento del proyecto, los resultados, el análisis, el contexto, observaciones, conclusiones y recomendaciones. En este proyecto trabajaron alumnos de las licenciaturas en Psicología, Mercadotecnia y Arquitectura

A systematic review and meta-analysis of cannabis-based medicines, cannabinoids and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain

We report a systematic review and meta-analysis of studies which assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference (SMD) effect size for each comparison and performed a random effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86 %). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective CB1, CB2, non-selective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol; THC), and PPAR-alpha agonists (predominantly palmitoylethanolamide; PEA) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase (FAAH) inhibitors, monoacylglycerol lipase (MGL) inhibitors and cannabidiol (CBD) significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low, therefore the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia

Hippocampal disruptions of synaptic and astrocyte metabolism are primary events of early amyloid pathology in the 5xFAD mouse model of Alzheimer's disease

Abstract Alzheimer’s disease (AD) is an unremitting neurodegenerative disorder characterized by cerebral amyloid-β (Aβ) accumulation and gradual decline in cognitive function. Changes in brain energy metabolism arise in the preclinical phase of AD, suggesting an important metabolic component of early AD pathology. Neurons and astrocytes function in close metabolic collaboration, which is essential for the recycling of neurotransmitters in the synapse. However, this crucial metabolic interplay during the early stages of AD development has not been sufficiently investigated. Here, we provide an integrative analysis of cellular metabolism during the early stages of Aβ accumulation in the cerebral cortex and hippocampus of the 5xFAD mouse model of AD. Our electrophysiological examination revealed an increase in spontaneous excitatory signaling in the 5xFAD hippocampus. This hyperactive neuronal phenotype coincided with decreased hippocampal tricarboxylic acid (TCA) cycle metabolism mapped by stable 13C isotope tracing. Particularly, reduced astrocyte TCA cycle activity and decreased glutamine synthesis led to hampered neuronal GABA synthesis in the 5xFAD hippocampus. In contrast, the cerebral cortex of 5xFAD mice displayed an elevated capacity for oxidative glucose metabolism, which may suggest a metabolic compensation in this brain region. We found limited changes when we explored the brain proteome and metabolome of the 5xFAD mice, supporting that the functional metabolic disturbances between neurons and astrocytes are early primary events in AD pathology. In addition, synaptic mitochondrial and glycolytic function was selectively impaired in the 5xFAD hippocampus, whereas non-synaptic mitochondrial function was maintained. These findings were supported by ultrastructural analyses demonstrating disruptions in mitochondrial morphology, particularly in the 5xFAD hippocampus. Collectively, our study reveals complex regional and cell-specific metabolic adaptations in the early stages of amyloid pathology, which may be fundamental for the progressing synaptic dysfunctions in AD