Epidural Stimulation Improvement of Neurogenic Bowel After Acute Spinal Cord Injury: A Large-Animal Study
Abstract
Up to 60% of spinal cord injury (SCI) patients experience neurogenic bowel dysfunction (NBD), with slowed motility of the colon, diminished food transit, constipation, and overflow incontinence. Thirty percent of SCI patients considered bowel disorders more burdensome than bladder or sexual dysfunction. Gastrointestinal (GI) complications account for 11% of serious inpatient hospital admissions in the SCI population. Myriad converging pathogenetic events lead to severe GI disturbances of the GI system after SCI. SCI disrupts the autonomic nervous system (ANS), which controls GI motility and regulates immune balance. Additionally, SCI creates gut dysbiosis, or an imbalance in good vs. bad bacteria, reduction of butyrate producing bacteria, increased intestinal permeability (leaky gut), bacterial translocation into organs, excess systemic inflammation and neurotoxicity. The combination of paralysis decreased autonomic function and dysbiosis work to maintain the NBS for which there are no effective treatments. The primary consequence of dysmotility is constipation and fecal impaction, a mainstay of SCI. Untreated constipation leads to colonic and rectal distension and autonomic dysreflexia which can be life-threatening. Bowel care programs can be burdensome for patients and caregivers, up to 2 hours daily and must be administered at scheduled intervals to prevent overflow incontinence. In the absence of new and better treatments, SCI patients will continue this schedule of bowel care for the rest of their lifetimes. When standard measures do not work, digital stimulation of the rectum is used to manually remove feces. This involves significant loss of privacy, as patients cannot do it themselves and often is administered by close family members. Due to the loss of independence and concomitant psychological burdens that accumulate over time, there is tremendous interest to use neuromodulatory technologies to achieve same or better effects than digital stimulation Recently, our group and others showed that spinal cord epidural stimulation (scES) placed at the thoracolumbar vertebral level optimized for standing (stand-scES) and stepping (step-scES) also improves bowel functions, in addition to motor gains in previously paralyzed patients. However, much remains unknown about spinal locations and parameters to more effectively use scES to treat NBD after SCI. Although there is growing evidence that thoracolumbar scES optimized for standing (stand-scES) and stepping (step-scES) improves bowel function, it remains unknown whether scES configurations specific for activating bowel networks (BscES) are more effective than those that activate locomotor networks (stand-scES) and stepping (step-scES) to achieve maximum benefit for bowel function after SCI. Our goals are to identify the best locations and parameters for activation of bowel networks for reducing neurogenic dysfunction and dysbiosis and inflammation after SCI and to investigate impact of early B-scES on bowel function after acute SCI. We hypothesize that early B-scES is more effective at improving 3-month colon motility outcomes than late B-scES and superior to early stand-scES and step-scES. A further goal is to assess effects of B-scES in the presence or absence of tributyrin (Tb). Tributyrin, a naturally occurring triglyceride in butter has been shown to repair gut dysbiosis after antibiotic or alcohol-induced dysbiosis. When given orally, Tributyrin is rapidly hydrolyzed to butyrate. Butyrate plays a key role in maintenance of intestinal epithelial lining and its absence has leads to failure to maintain intestinal mucosa; lining and barriers with resultant bacterial translocation, immune cell and cytokine activation, systemic inflammation, and metabolic derangements. This 3-year study is expected to provide evidence of the best neuromodulatory strategy for improving bowel function after SCI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010348
Entities
People
- Maxwell Boakye
Organizations
- United States Army
- University of Louisville