Drosophila Glypicans Dally And Dally-Like Control Injury Induced Allodynia

Over 100 million people suffer from the effects of chronic pain in the United States alone. This burden also impacts the U.S. economy; 600 billion dollars annually is spent on medical care, medications, and lost productivity in the workplace. Current opioid treatments cause adverse effects including nausea, constipation, tolerance, and addiction liability. The neuroplastic process of pain sensitization is thought to perpetuate chronic pain, but too little is known about its mechanisms. Components of the pathways that connect injury and pain sensitization are likely to be valuable targets for novel medications for the relief or prevention of chronic pain. Utilizing the Drosophila melanogaster cell targeting and RNA interference toolkit, our lab investigates the Bone Morphogenetic Protein (BMP) pathway and its role in ultraviolet light (UV) injury-induced nociceptive sensitization. BMPs are well known as secreted developmental morphogens that control imaginal disc patterning by binding membrane bound receptors of target cells, but other functions are known. We have previously utilized a candidate gene approach to identify BMP signaling components used in nociceptive neurons to modulate injury-induced allodynia in Drosophila (Follansbee et al, 2017). The present study investigates the necessity of additional regulators of the BMP pathway in the formation of UV injury-induced sensitization. The components of the BMP pathway are highly conserved and, because pain sensitization underlies chronic pain, these genes show potential to represent novel therapeutic targets in humans challenged by chronic pain

Examining Pre-Service Teacher Mental Health Training and Self-Efficacy at One American University

With rates of mental health concerns among students increasing, teachers are expected to support the mental health needs of students in their classrooms. However, practising teachers report low levels of ability to support students with mental health needs. Mental health training during pre-service teacher preparation could proactively prepare teachers to support student mental health. The current study examined the level of mental health training that pre-service teachers receive, their reported level of mental health self-efficacy, and how self-efficacy differs based on exposure to mental health training. We surveyed undergraduate pre-service teachers at a public university in the United States Midwest (n = 105). Overall, participants reported minimal levels of mental health training that varied by year in the program. Most participants indicated some confidence in their capacity to successfully support students’ mental health needs. Results suggest that participants who reported some mental health training exposure also reported higher levels of self-efficacy to support students with mental health needs compared to participants with a lack of mental health training exposure. Implications for training pre-service teachers are reviewed

Heat-shock protein 90 (Hsp90) promotes opioid-induced anti-nociception by an ERK mitogen-activated protein kinase (MAPK) mechanism in mouse brain

Recent advances in developing opioid treatments for pain with reduced side effects have focused on the signaling cascades of the μ-opioid receptor (MOR). However, few such signaling targets have been identified for exploitation. To address this need, we explored the role of heat-shock protein 90 (Hsp90) in opioid-induced MOR signaling and pain, which has only been studied in four previous articles. First, in four cell models of MOR signaling, we found that Hsp90 inhibition for 24 h with the inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) had different effects on protein expression and opioid signaling in each line, suggesting that cell models may not be reliable for predicting pharmacology with this protein. We thus developed an in vivo model using CD-1 mice with an intracerebroventricular injection of 17-AAG for 24 h. We found that Hsp90 inhibition strongly blocked morphine-induced anti-nociception in models of post-surgical and HIV neuropathic pain but only slightly blocked anti-nociception in a naive tail-flick model, while enhancing morphine-induced precipitated withdrawal. Seeking a mechanism for these changes, we found that Hsp90 inhibition blocks ERK MAPK activation in the periaqueductal gray and caudal brain stem. We tested these signaling changes by inhibiting ERK in the above-mentioned pain models and found that ERK inhibition could account for all of the changes in anti-nociception induced by Hsp90 inhibition. Taken together, these findings suggest that Hsp90 promotes opioid-induced anti-nociception by an ERK mechanism in mouse brain and that Hsp90 could be a future target for improving the therapeutic index of opioid drugs.12 month embargo; published online: 27 April 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]