Exploring Sacral Spinal Nerve Root Stimulation (SNS) to Induce Defecation for Managing Autonomic Dysfunction (AD) and Associated Sequelae in Spinal Cord Injury (SCI)
Mariana Tostado
Background: Spinal cord injury (SCI) is a devastating condition characterized by sensory, motor, or autonomic dysfunction below the level of injury, affecting 250,00 to 500,000 individuals per year1. SCI typically arises from traumatic events including motor vehicle accidents, falls, sports injuries, or acts of violence1. Individuals sustaining SCI experience significant loss of function and disability, ultimately impacting independence and overall quality of life1. SCI can result in a spectrum of life-altering symptoms including paralysis, and cardiovascular, bowel, bladder, and autonomic dysfunction1. Autonomic dysreflexia (AD) is a significant autonomic dysfunction affecting 70-90% of individuals sustaining injury to the spinal cord at or above the T6 level2. AD occurs in response to noxious stimuli, such as a bowel impaction, and results in a life-threatening surge in blood pressure, posing severe implications including hemorrhages and cardiopulmonary failure2. Despite therapeutic interventions for managing fecal impaction, a gap remains in preventing the onset of noxious stimuli altogether.
Objective: The objective of this review was to analyze literature on the role of sacral nerve root stimulation (SNS) in promoting defecation and colonic motility. Specifically, the review explores the effects of SNS on colonic pressure, serotonin (5-HT), and inducible nitric oxide synthase (iNOS) levels, and their respective impact on gastrointestinal function.
Search Methods: An online search was conducted through the PubMed database utilizing the following keywords: “Spinal cord injury”, “Sacral nerve stimulation”, “Autonomic dysreflexia”, “bowel dysfunction”.
Results: The first study conducted SNS by placing electrodes on the dorsal and/or ventral roots of anesthetized cats at the S1 through S3 spinal cord levels. Stimulus pulses between 1 and 50 Hz were applied3. Using balloon catheters in the proximal and distal colon, contraction pressure was measured3. Further, glass marbles were inserted to the rectum and ability of elimination was observed3. Researchers found stimulation of the S2 ventral and dorsal roots with 7 Hz elicited significant colon contraction compared to S1 and S33. Stimulating ventral S2 spinal roots concurrently with 7 Hz also induced elimination of 1 to 2 marbles from the rectum3. The following study assessed SNS and resulting levels of 5-HT in rat models. Following 14 days of stimulation at the S3 nerve root, rat models with acute SCI showed upregulation of 5-HT3AR and 5HT4R mRNA and protein in the colon and sacral cord4. Upregulation of the 5-HT/5-HT3AR/5-HT4R axes demonstrated improvement in the defecation reflex and recovery of colonic transmission function in rats with SCI4. The final study observed the role of iNOS in rat models with SCI at the T10 level. Following 14 days of SNS, the differences in nNOS protein levels, mRNA, and nitric oxide (NO) content in the colon and sacral cord were quantified using western blot, immunohistochemistry, nitrate reductase method, and real-time PCR5. SCI rats had significantly higher levels of nNOS5. As a result, SCI rats suffered from decreased fecal matter elimination as well as longer bowel movement time from start to finish5. SNS was found to downregulate nNOS expression in the colon and sacral spinal cord, resulting in lower NO content compared to the SCI group5. High levels of iNOS and NO were found to be toxic to the interstitial cells of Cajal (ICC) which are key cells of the submucosal plexus, involved in peristalsis.
Conclusions: While it is promising to see an opportunity on the horizon to develop minimally invasive therapeutics targeting bowel dysfunction in SCI patients, it poses many questions moving forward on the specificities of treatment plans. The articles explored had only one thing in common, and that was the use of SNS. However, the models, frequencies, SNS levels, and results varied across research groups, highlighting the need for further investigation and standardization.
Works Cited
- Quadri SA, Farooqui M, Ikram A, et al. Recent update on basic mechanisms of spinal cord injury. Neurosurg Rev. 2020;43(2):425-441. doi:10.1007/s10143-018-1008-3
- Balik V, Šulla I. Autonomic Dysreflexia following Spinal Cord Injury. Asian J Neurosurg. 2022;17(2):165-172. Published 2022 Aug 25. doi:10.1055/s-0042-1751080
- Wang J, Shen Z, Shen B, et al. Defecation induced by stimulation of sacral S2 spinal root in cats. Am J Physiol Gastrointest Liver Physiol. 2021;321(6):G735-G742. doi:10.1152/ajpgi.00269.2021
- Zhu Y, Cheng J, Yin J, et al. Effects of sacral nerve electrical stimulation on 5‑HT and 5‑HT3AR/5‑HT4R levels in the colon and sacral cord of acute spinal cord injury rat models. Mol Med Rep. 2020;22(2):763-773. doi:10.3892/mmr.2020.11148
- Chen B, Guo J, Ni Y, et al. Effects of Sacral Nerve Stimulation on Neuronal Nitric Oxide Synthase in the Colon and Sacral Cord of Rats With Defecation Disorder After Spinal Cord Injury. World Neurosurg. 2022;164:e214-e223. doi:10.1016/j.wneu.2022.04.080