Ting, Jordyn Elizabeth
(2024)
Rational Selection of Stimulation Parameters for Promoting Analgesia Through Dorsal Root Ganglion Stimulation.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Chronic pain affects nearly 100 million people in the United States, resulting in significant morbidity, lowered quality-of-life, and unemployment that amounts to over $500 billion in healthcare and productivity costs every year. The use of opioid therapies in treating chronic pain has contributed to a growing opioid overdose epidemic that has motivated substantial research into nonpharmacologic therapies, including neurostimulation. In recent years, dorsal root ganglion stimulation (DRGS) has emerged as an alternative therapy for some patients suffering from chronic pain. Widespread clinical adoption of DRGS has been hindered, however, by the complexity of the electrode implantation procedure and a lack of understanding surrounding the mechanisms underlying DRGS-mediated analgesia, making it difficult to select the appropriate stimulation parameters for therapeutic efficacy. In this dissertation, we evaluate a novel, injectable electrode, the Injectrode, for delivering DRGS and investigate afferent fiber recruitment by DRGS to develop a better understanding of its mechanisms. In the first study, we demonstrated that the highly conformable Injectrode performed similarly to a more traditional electrode in recruiting large-diameter afferent fibers, which are thought to contribute to pain relief when activated by stimulation. Next, we explored how variations in stimulation parameters influence the type, strength, and stability of DRG and spinal neuron recruitment during DRGS. We showed a progressive, frequency-dependent attenuation in the activation of large-diameter Aα/β-fibers during tonic DRGS that may be attributed to increased excitation thresholds that occurred during sustained periods of stimulation, Finally, we found that 20 Hz DRGS produced a greater suppression of spinal responses to both innocuous and noxious mechanical stimulation than 100 Hz DRGS, indicating that inhibitory gating in the dorsal horn may play a primary role in DRGS-mediated analgesia. Taken together, these studies suggest that DRGS delivered at lower frequencies is more effective in maintaining a sustained recruitment of the large-diameter fibers required to elicit gating mechanisms in the dorsal horn and that employing these lower frequencies may enhance the therapeutic efficacy of DRGS.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
3 June 2024 |
| Date Type: |
Publication |
| Defense Date: |
23 February 2024 |
| Approval Date: |
3 June 2024 |
| Submission Date: |
10 February 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
154 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
neuromodulation, dorsal root ganglion stimulation, electrical stimulation |
| Date Deposited: |
03 Jun 2024 14:36 |
| Last Modified: |
03 Jun 2024 14:36 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/45796 |
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