Acute and chronic pain conditions are often debilitating, inflicting severe physiological, emotional and economic costs and affect a large percentage of the global population. However, the development of therapeutic analgesic agents based primarily on targeted drug development has been largely ineffective. An alternative approach to analgesic development would be to develop low cost, high throughput, untargeted animal based behavioral screens that model complex nociceptive behaviors in which to screen for analgesic compounds. Here we describe the development of a behavioral based assay in zebrafish larvae that is effective in identifying small molecule compounds with analgesic properties. In a place aversion assay, which likely utilizes supraspinal neuronal circuitry, individually arrayed zebrafish larvae show temperature-dependent aversion to increasing and decreasing temperatures deviating from rearing temperature. Modeling thermal hyperalgesia, the addition of the noxious inflammatory compound and TRPA1 agonist allyl isothiocyanate sensitized heat aversion and reversed cool aversion leading larvae to avoid rearing temperature in favor of otherwise acutely aversive cooler temperatures. We show that small molecules with known analgesic properties are able to inhibit acute and/or sensitized temperature aversion.
Background: Although some geriatric trauma patients may be low-risk for complications, poor outcomes are pronounced if complications do occur. Prevention in this group decreases the risk of excess morbidity and mortality. Methods: We performed a case-control study of trauma patients 65 years or older treated from January 2015 to August 2016 at a level I trauma center with a Trauma Quality Improvement Program (TQIP) predicted probability of complication < 20%. Cases had one of the following complications: unplanned admission to the intensive care unit (ICU), unplanned intubation, pneumonia, or unplanned return to the operating room. Two age-matched controls were randomly selected for each case. We collected information on comorbidities, home medications, and early medical care and calculated odds ratios using multivariable conditional logistic regression. Results: Ninety-four patients experienced unplanned admission to ICU (N=51), unplanned intubation (N=14), pneumonia (N=21), and unplanned return to OR (N=8). The 188 controls were
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