Date of Award


Document Type

Open Access Thesis

Degree Name

MS in Physician Assistant Studies (PA)


Physician Assistant Studies

First Advisor

Kristen Lindvall, PA-C


Background: Chronic pain and disease are prevalent, affecting 51.6 million people in 2023. Therefore, due to the high complexity of chronic disease, many providers try different interventions to alleviate pain and improve their patient's quality of life. The limbic system is a critical component of the brain involved in pain perception and emotional regulation. With an overactive limbic system, the perception of pain is enhanced and continues to cause discomfort for the patient. By retraining the limbic system to alter the fight or flight response, a significant reduction in pain can be achieved, which results in better emotion regulation. The primary interventions considered for limbic system retraining are neurofeedback and electrical stimulation. Purpose: This review aims to evaluate the efficacy of limbic system retraining and neuroplasticity in managing chronic pain and disease. Methods: The author conducted an extensive literature review to evaluate the evidence and conducted a thorough annotated bibliography. Inclusion criteria for this study included articles that contained the key terms, were original research, could be obtained freely, and were published later than 2019. Any articles that didn’t meet the inclusion criteria were excluded. Data was collected using these key terms: amygdala neuromodulation, amygdala and insula retraining, limbic system neuromodulation, amygdala and chronic pain, limbic system retraining, neuroplasticity, and chronic pain management. Further, the following search engines were used to obtain articles: PubMed, Google Scholar, Jane Biosematic, National Institute of Health (NIH), UpToDate, and Science Direct. Data gathered was synthesized by evaluating the study's sample size and the statistical significance of the results while considering any potential bias. A limitation of the data collection was that only freely available articles through Augsburg Library sources were reviewed. Results: After a thorough literature review, evidence supports the efficacy of limbic system retraining and neuroplasticity using neurofeedback and electrical stimulation. Of the articles reviewed, 19 met inclusion criteria, with 11 supporting neuromodulation using neurofeedback and eight for electrical stimulation. Studies ranged in sample size, and of the 11 articles supporting neurofeedback for neuromodulation, all were randomized controlled studies, with three not randomized. Further, of the eight randomized controlled studies, two were double-blind studies. Additionally, of the eight papers supporting the use of electrical stimulation, all were randomized controlled, with three being double-blinded. Evidence to support limbic system retraining using neurofeedback included amygdala plus insula retraining with MBSR and using real-time fMRI and amygEFP. These articles have shown efficacy in reducing pain and overall functional impairment. For patients with post-traumatic stress disorder, a significant reduction in symptoms of 75% continued for up to 6 months. When considering articles supporting electrical stimulation, the results indicated that transcutaneous direct stimulation is effective for neuromodulation and reduced abdominal pain for inflammatory bowel disease. Additionally, 73% of participants noted reduced pain for patients who underwent electrical intramuscular stimulation. Further, transcutaneous vagus nerve stimulation also proved effective in modulating pain and reducing the number of chronic migraine attacks. Discussion: A review of the literature and studies noted a few limitations. Across multiple papers, the primary limitation was the small sample size. Additional considerations were specific to each modality. The primary limitation of articles supporting neurofeedback for neuromodulation included the time to learn neurofeedback techniques. However, other limitations had too few fMRI scans, which were noted in two studies, and there was a concern about not considering the control variable of different therapists for teaching MBSR. Additionally, electrical stimulation papers also emphasized the need for research conducted over a more extended period, varied participants, and a greater sample size. Further, for the vagus nerve articles, the primary future consideration was to evaluate the influence of the sham intervention on the overall results. In conclusion, limbic system retraining and neuroplasticity are possible and effective. However, additional research is needed to evaluate the efficacy across a larger population and consider the long-term outcomes and benefits.


SC 11.PAS.2023.Carr.J