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Graduation Term

2015

Degree Name

Doctor of Philosophy (PhD)

Department

School of Biological Sciences

Committee Chair

Wolfgang Stein

Committee Member

David Cedeno

Abstract

Electrical stimulation has been documented as a therapy for treating pain as early as 47 AD. As neurons communicate via electrical as well as chemical signals, it stands to reason that an electrical stimulus could have an effect on molecular pathways involved in alleviating pain. The work compiled in this dissertation was focused on genes known for their involvement in initiating, developing, and maintaining a chronic neuroinflammatory environment and their changes in expression following the use of two different electrical stimulation therapies that are already clinically employed.

Pulsed radiofrequency (PRF) utilizes electromagnetic energy in one brief session to induce pain relief that on average persists for several months. The fact that PRF applied for a few minutes can induce such long lasting relief indicates that it affects transcriptional and/or translational pathways aside in addition to a temporary disruption of electrical pain signal propagation. Little research has been done to determine what happens at the molecular level within the nervous system following PRF therapy. This dissertation demonstrates for the first time that PRF reverses expression of several inflammatory genes that coincide with reduced mechanical sensitivity. Additionally, these changes were observed along the nociceptive pathway indicating that PRF applied in the periphery induces a local and ascending effect along the involved neural pathway.

Spinal cord stimulation (SCS) employs a chronically implanted device that utilizes electric field energy applied to the spinal cord to ameliorate pain. Clinically, efficacy is determined by overlaying the perceived paresthesia and the site of pain. However, when SCS is turned off there is a brief period of extended pain relief indicating that it is not merely a perceived block of the pain signal. We were able to create the first chronically implanted animal model that receives continuous stimulation, and do follow-up gene expression analyses on the same set of genes reported in the PRF studies.

Both electromagnetic and electric field stimulation resulted in attenuating the mechanical sensitivity induced by the injury model. Additionally, both therapies modulated gene expression at the local site of stimulation as well as along the nociceptive pathway. This dissertation demonstrates that there is at least some degree of similarity in neural response to electromagnetic or electric field stimulation in regulating chronic pain.

Access Type

Dissertation-ISU Access Only

DOI

http://doi.org/10.30707/ETD2015.Tilley.D

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