Date of Completion

6-27-2019

Embargo Period

12-23-2019

Keywords

pain; RNAseq; sham operation; FACS; real-time PCR; von Frey; open field

Major Advisor

Richard E. Mains

Associate Advisor

Barbara Kream

Associate Advisor

Eric Levine

Associate Advisor

James Li

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

The work presented here begins to provide insight into the underlying mechanisms that contribute to the transition from acute to chronic pain. Our work employed spinal cord injury (SCI) as a unique model to study chronic pain, and to enhance our knowledge of the transcriptional changes that occur following injury. The studies herein support the idea that SCI alters genetic, cellular, and molecular pathways at distal sites (below the site of injury) such as skin, muscle, and the sensory neurons that project to these regions. We provide evidence that a specific population of sensory neurons located in distal dorsal root ganglia exhibit significant transcriptional changes that are relevant to the onset of chronic pain. By enhancing our knowledge regarding the changes that occur at different time points, within different tissues, and within specific cell populations, we can better understand why chronic pain develops weeks to months after injury in patients. In particular, our work on transcriptional profiling of specific sensory neurons projecting to the skin below the level of injury, in comparison to whole tissue analysis, emphasizes how injury does not impact all cell populations in the same way. A multifaceted approach is essential for the development of new treatment strategies and models for patients, in an effort to prevent irreversible changes in pain signaling before they occur.

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