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Parada, C. A.

Publications and source records attributed to Parada, C. A..

3 recordsLinked to original sources

Measuring Joint Pain Through Tibio-Femoral Flexion: technique validation and assessment of behavior in response to different analgesics in rats

BackgroundAssessing knee joint pain in experimental OA (EOA) models remains a significant challenge. Our study demonstrates that the use of an adapted electronic von Frey (aVF) device, featuring a modified tip, surpasses the standard von Frey (sVF) in detecting knee joint pain behavior and evaluating the efficacy of analgesic treatments in OA model induced by monoiodine acetate (MIA). ResultsThe sVF was able to induce a behavior profile in naive animals characterized by a hind paw flinching and withdrawal reflex. This behavioral response was affected by intraplantar lidocaine, which prone to the increase in mechanical thresholds related to sVF and validate it as pain related behavior. On the aVF method, the animals displayed no alterations at their mechanical thresholds in presence or absence of lidocaine, suggesting minimal stimulation of hind paw by the modified methodology. In animals where an osteoarthritic phenotype was induced by MIA, the aVF was able to detect a significant reduction on joint mechanical thresholds. The behavior linked to aVF was significantly affected by systemic delivery of morphine, confirming a nociceptive-like phenotype and suggesting a pain behavior predominantly triggered by joint flexion. The aVF was also able to detect an analgesic profile in MIA-OA rats treated with dexamethasone, LPS-RS, fucoidan, and morphine, indicating effectiveness in measure different the response profile triggered by analgesic drugs that affect joint pain perception. ConclusionsOur results suggest aVF as a more appropriate method to evaluate joint pain in rats.

neuroscience↗

Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome.

Meningiomas, the most common intracranial tumor, though mostly benign can be recurrent and fatal. WHO grading does not always identify high risk meningioma and better characterizations of their aggressive biology is needed. To approach this problem, we combined 13 bulk RNA-Seq datasets to create a dimension-reduced reference landscape of 1298 meningiomas. Clinical and genomic metadata effectively correlated with landscape regions which led to the identification of meningioma subtypes with specific biological signatures. Time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape where nearest neighbors predict outcome. This study highlights the utility of combining bulk transcriptomic datasets to visualize the complexity of tumor populations. Further, we provide an interactive tool for understanding the disease and predicting patient outcome. This resource is accessible via the online tool Oncoscape, where the scientific community can explore the meningioma landscape.

cancer biology↗

Physical Activity Induces Nucleus Accumbens Genes Expression Changes Preventing Chronic Pain Susceptibility Promoted by High-Fat Diet and Sedentary Behavior in Mice

High-fat diet (HFD)-induced obesity was reported to increase pain behavior independent of obesity status in rats, whereas weight loss interventions such as voluntary physical activity (PA) for adults with overweight or obesity was reported to promote pain reduction in humans with chronic pain (CP). However, is unknown whether an HFD and sedentary (SED) behavior is underlying to CP susceptibility and whether voluntary PA can prevent it. Moreover, differential gene expression in the nucleus accumbens (NAc) is considered to play a crucial role in CP susceptibility. The present study used an adapted model of the inflammatory prostaglandin E2 (PGE)-induced persistent hyperalgesia (PH-ST) protocol for mice, an HFD, and a voluntary PA paradigm to test these hypotheses. In addition, we performed a transcriptome in the NAc and a gene ontology enrichment tools to investigate the differential gene expression and identify the biological processes associated with CP susceptibility tested here. Our results demonstrated that HFD and sedentary behavior promoted CP susceptibility, which in turn was prevented by voluntary PA, even when the animals were fed an HFD. Transcriptome in the NAc found 2,204 differential expression genes related CP susceptibility promoted by HFD and sedentary behavior and prevented by voluntary PA. The gene ontology enrichment revealed 41 biological processes implicated in CP susceptibility. Analyzing collectively those biological processes, our results suggested that genes related to metabolic and mitochondria stress were up-regulated in the CP susceptibility group, whereas genes related to neuroplasticity and axonogenesis were up-regulated in the CP prevented group. These findings provide pieces of evidence that an HFD and sedentary behavior promoted gene expression changes in the NAc related to neurodegeneration and those changes were also underlying to CP susceptibility. Additionally, our findings confirmed other findings supporting the crucial role of voluntary PA to prevent CP susceptibility and add novel insights of differential gene expression in the NAc related to neuroplasticity.

neuroscience↗