PVR, A Growth Factor Receptor, Plays A Role In Thermal Nociception

Across the globe, chronic pain affects approximately 1.5 billion people. In the United States, it costs approximately $600 billion dollars every year in lost labor, treatments, and healthcare. Therefore, it is important to identify and characterize the molecular pathways and signaling molecules involved in pain to enhance our understanding of why chronic pain occurs and how we can improve the existing treatments. This research project aims to contribute to this goal by determining the role Pvr, a growth factor receptor, plays in thermal nociception in Drosophila melanogaster, commonly known as the fruit fly. Drosophila is used in this project as they are amenable to transgenesis, allowing for modification of gene function; and they have been widely used for studying nociception. Previous experiments have established that Pvr is required for regulating mechanical nociception; however, there have not been any studies detailing the role of Pvr in thermal nociception. This project aims to knock down and overexpress Pvr in the multidendritic neurons of Drosophila and assess the effects produced on thermal nociception. The results of the thermal nociception assay show that knockdown and dominant negative expression of Pvr produce a significant defect in thermal nociception. Moreover, Pvr overexpression and constitutive activation of Pvr caused in- creased sensitivity to noxious stimuli. The results of this assay showed that Pvr is necessary and sufficient to promote sensitivity of the neurons to thermal stimuli. This study establishes a novel role for a conserved signaling pathway, Pvf/Pvr in regulating thermal nociception.The results of this study indicate overlap in mechanisms that regulate thermal and mechanical nociception.