Date of Award

5-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

Committee Chair

Riyi Shi

Committee Member 1

Oyuang Zhang

Committee Member 2

Jeffrey Youngblood

Committee Member 3

Eric Nauman

Abstract

Neuropathic pain after spinal cord injury (SCI) presents a complex clinical challenge, affecting millions with no satisfactory treatment options currently available. Much of the recent research focuses on a wide variety of endogenous mechanisms that can contribute to pain, but have yet to produce positive results in clinical studies. This dissertation focuses on the role of a highly reactive and toxic aldehyde, acrolein, in initiating, instigating, and perpetuating neuropathic pain after spinal cord injury. Acrolein is shown to mimic damage caused by an injury, in the absence of mechanical trauma. Additionally, removing it using acrolein scavengers can mitigate neuropathic pain-like behaviors. This dissertation also investigates the dynamic response of not only acrolein, but also a cation channel that is associated with neuropathic pain, TRPA1, and a pro-inflammatory chemokine, MCP-1, that may be involved in the transition from acute to chronic pain. Endogenous mechanisms of neuropathic pain development may not be the only contributing factors to the persistence of post-SCI neuropathic pain. Few studies have investigated the effects of exogenous factors that can contribute to pain. One such factor, cigarette smoke, has been featured in clinical reports of post-SCI neuropathic pain where increases in neuropathic pain were observed during periods of smoking. Cigarette smoke happens to contain, among many toxic chemicals, acrolein. Until this study, investigations linking cigarette smoke and the biochemical mechanisms of post-SCI pain had yet to be procured. We hypothesized that respiratory exposure to acrolein from cigarette smoke contributes to post-SCI hypersensitivity in a mechanistically similar manner to acrolein-mediated pain development (acute) and persistence (chronic). This study correlates acrolein inhalation with neuropathic pain behavior and deepened the understanding of the underlying biochemical mechanisms behind acrolein-mediated pain. It also demonstrates that exposure to cigarette smoke delays the exacerbation of neuropathic pain after SCI. The ultimate goal of this research endeavor has been to provide evidence for the potential development of more safe and effective treatments for post-SCI neuropathic pain.

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