Date of Award

8-2015

Rights

© 2015 Taylor L. Follansbee

Document Type

Thesis: UNE Community Access Only

Degree Name

Master of Science in Biological Sciences

Department

Biological Science

First Advisor

Geoffrey Ganter

Second Advisor

Lei Lei

Third Advisor

Ian Meng

Abstract

In the United States alone over 100 million people suffer from chronic pain and unfortunately, even still, there is a lack in scientific understanding for the mechanisms of abnormal pain sensitivity. The present study utilized a candidate gene approach to identify novel components required for modulation of the tissue damage induced pain sensitization pathway in Drosophila melanogaster. We have shown that RNAi silencing of decapentaplegic (dpp), a member of the Bone Morphogenetic Protein (BMP) signaling pathway, specifically in the class IV multidendritic nociceptor neurons significantly attenuated UV-induced nociceptive sensitization. Furthermore, overexpression of dpp in nociceptor neurons was sufficient to induce sensitization in the absence of tissue damage. We then show that the dpp receptors are required on the nociceptor neuron in order to produce allodynia, demonstrating that dpp is signaling to the very neuron that produced it. Lastly, we show that this BMP pathway is utilizing the canonical signaling SMAD factors to induce allodynia. We show that the effects of BMP signaling were largely specific to the sensitization pathway and not to normal nociception or dendritic morphology. Thus, we have shown that dpp plays a crucial and novel role in sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates it seems likely that the genes we have analyzed represent potential therapeutic targets applicable to humans.

Comments

This work is currently intended for the personal educational use of University of New England students, faculty, and staff only. It will become available for use by the public in February, 2018.

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