Chronic refractory gastrointestinal (GI) motility disorders are a significant burden on the healthcare system, acting as a large public health issue with significant impact on the quality of life in both the pediatric and adult population. Control systems of gastrointestinal motility are complex and involve coordination of smooth muscle contraction and relaxation, which the autonomic nervous system is largely responsible for. Gaps in the diagnosis process, such as overlooking autonomic function, has left patients with diminished quality of life and limited treatment options. Many patients in the clinic have experienced injury within the spinal cord and we hypothesized that GI symptoms might be related to spinal injury causing disruption of sensory and/or motor nerves of the autonomic nervous system. Our objective became to better understand the specific location and nature of spinal injuries and GI symptoms, as completed through the development of a self-report questionnaire. Main findings suggest symptoms indicative of T3-T9 and T10-L2 spinal pathology. COVID-19 did not allow for in-clinic neuromodulation with autonomic assessments, resulting in experiments remotely assessing at-home neuromodulation treatment for GI symptoms with suspected spinal autonomic dysfunction. At-home neuromodulation was not suitable for many patients, but those who were able to manage it showed highly promising results. After years of suffering, transcutaneous electrical nerve stimulation alleviated symptoms, particularly postprandial abdominal pain, constipation, vomiting and nausea. I discuss what we learned to set us up for successful at-home treatment, and we will use all information to design randomized controlled trials to prove the benefit of TENS. The present work offers significant information on the relationship of thoracolumbar spinal pathology and complex GI symptoms, which is now used in the clinic in the diagnosis process of GI dysmotility. In addition, we have learned how to conduct at-home treatment using TENS, which allows us to execute future studies. / Thesis / Master of Science (MSc) / There are gaps in the diagnosis process of complex gastrointestinal (GI) dysmotility disorders, including lack of testing of autonomic function, leaving patients suffering with diminished quality of life with unsuccessful treatment attempts. As many patients also experience injury or conditions of the spine, I have hypothesized that GI symptoms may be related to spinal injury-induced dysfunction of the autonomic nervous system. Experimental models aim to understand the location and nature of spinal pathology with GI symptoms for future diagnoses, as well as potential treatment options such as neuromodulation. Findings of this thesis suggest symptoms indicative of particular thoracolumbar spinal pathology and promising results of transcutaneous electrical nerve stimulation (TENS) to alleviate GI symptoms, including T3-T9 and T10-L2 spinal pathology-related postprandial abdominal pain, constipation, nausea, and vomiting. This work offers information for the diagnostic process of GI dysmotility and the future design of clinical trials of neuromodulation therapies.

Introduction: Functional motility disorders of the colon are poorly defined. Hence, patients with chronic colonic motor dysfunction are treated or undergo surgery without proper diagnosis. Most colonic motility assessment centers around the largest propagating motor pattern in the colon- the High Amplitude Propagating Pressure Wave (HAPW). However, there is no consensus regarding a definition of this important motor pattern. Additionally, no consideration is given to other aspects of colonic motility such as colo-ano-rectal coordination and control by the autonomic nervous system (ANS). The aim of this thesis was to improve understanding of HAPWs and other features of colonic motility in health and constipation, understand how autonomic dysfunction is related to observations in patients, and evaluate the effect of neuromodulation of the ANS. Methods: Motility was assessed in healthy volunteers and patients using water-perfused High Resolution Colonic Manometry (HRCM). To assess the association between ANS and colonic motor activity Heart Rate Variability (HRV) was measured in patients. Spatiotemporal maps were created using HRCM to analyse and quantify colonic motor activity following baseline, and interventions which included proximal balloon distention, meal, and rectal bisacodyl. Low-Level Light Therapy (LLLT) was also applied during HRCM as a method of neuromodulation, to observe its effect on colonic motility. Results: Normal HAPWs are those which have an amplitude of more than 50 mmHg and belong to one of 3 categories: proximally originating, proximal continuing, and transverse/descending. The best intervention sequence to generate these during HRCM assessment is baseline, proximal balloon distention, meal, rectal bisacodyl. Based on their responses to these interventions and the type of HAPWs present, patients could be classified into strong responder, weak responder and non-responder groups. Overall, patients in the strong responder group were most similar to healthy volunteers both with regard to motility and ANS control. Conversely, the weak and non-responders had showed decreased or no motility with decreased parasympathetic input and occasionally sympathetic inhibition. Additionally, other features of motility such as the sphincter of O'Beirne, and lack of colo-ano-rectal coordination were found to lead to constipation even in presence of normal HAPWs. LLLT shows promise in initiating colonic motor activity through neuromodulation of the sacral defecation center. Conclusions: HAPWs can be defined into one of three categories and used to categorize patients based on their HAPW response to different interventions. However, other aspects of colonic motility such as the colo-ano-rectal coordination and autonomic nervous system control of colonic motility should be taken into consideration in diagnosis of constipation, as they can point towards more non-invasive treatment methods such as neuromodulation using LLLT. / Thesis / Master of Science in Medical Sciences (MSMS)