The effect of spinal cord injury on vagal afferents.

Spinal cord injury (SCI) is a significant public health concern that leaves patients with a multitude of life-long disabilities. Major complications of SCI apart from paralysis, include deficits in bladder and bowel function. Lower urinary tract dysfunction continues to remain a top priority issue affecting quality of life for this population. The majority of visceral organs receive a dual sensory innervation from both spinal nerves as well as the vagus nerve. Following SCI, the vagus nerve is a potential pathway through which information from regions below the level of a spinal injury can travel directly to the brainstem, bypassing the spinal cord. The effect of SCI on the vagus nerve and the tissue it supplies has not been thoroughly examined. In order to advance bladder management after SCI, a thorough understanding of its neural control following chronic injury is needed to ultimately improve existing therapeutic options, as well as develop novel interventions that take advantage of this extraspinal route. The objective of this project was to describe the anatomical, neurochemical, and electrophysiological profiles of vagal innervation of the rat urinary bladder. Initially, the first study identified both single and double-labeled vagal afferents supplying the rat bladder and distal colon in the nodose ganglion (NG). The degree of neural innervation to the colon also was assessed, as a single axon that dichotomizes and innervates both organs can serve an important role for mediating both normal physiological and pathological reflexes. Following chronic SCI, we evaluated potential plasticity in subsets of NG neurons which contain projections that bypass the spinal cord from visceral organs, including those projections that specifically supply the bladder. Vagal sensory cell bodies displayed an increase in P2X3 expression and a decrease in IB4 binding, which also held true for many neurons innervating the bladder. Bladder-innervating neurons also displayed altered membrane electrophysiological properties, suggesting they are responsive to a chronic spinal injury. Even though SCI does not directly sever the vagus nerve, our results indicate vagal afferents, including those innervating the bladder, exhibit neurochemical plasticity post-injury that may have implications for visceral homeostatic mechanisms and nociceptive signaling

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury

<div><p>Objective</p><p>Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs’ pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury).</p><p>Study design</p><p>Prospective cohort study; pilot trial with small sample size.</p><p>Methods</p><p>Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart.</p><p>Results</p><p>Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants.</p><p>Conclusions</p><p>These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT03036527" target="_blank">NCT03036527</a></p></div

Bladder capacity data summary.

<p>Bladder filling ceased and capacity measured (leak + residual volumes) with the occurrence of either spontaneous urine leakage (n = 5; reflex void), autonomic dysreflexia (n = 2; Participants A60 and C42) or a voluntary void following a strong urge (AIS D Participant C43). (A) A comparison of pre- and post-training bladder capacity values in each of the eight participants. A binomial proportion test indicates that a significant majority of the research participants demonstrated an improvement in bladder capacity (vs. random occurrence, p < .05). Note that research participant B23 had a suprapubic catheter and thus, the increase in capacity was incremental. (B) Bladder capacity increased significantly post-training (p = .02, 155.4 ± 76.1 vs 278.5 ± 147.8 ml).</p

LUT elements adapted from international SCI data set [74].

<p>LUT elements adapted from international SCI data set [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190998#pone.0190998.ref074" target="_blank">74</a>].</p

Summary of cystometry data for usual care participants.

<p>Summary of cystometry results for the four non-trained research participants at two different time points. No significant differences were found between any parameters. Shown are group means (± SD) for capacity, leak point pressure (LPP), maximum detrusor pressure (MDP) and contraction duration (CD).</p

Leak point pressure data summary.

<p>Intravesical bladder pressure values at the onset of leak/void in six of eight research participants during cystometry. (A) A comparison of pre- and post-training bladder leak pressure values in each of the six participants. A binomial proportion test indicates that a significant majority of the research participants demonstrated an improvement in overall bladder leak point pressure (vs. random occurrence, p < .05). (B) The intravesical pressure at the time the leak/void was recorded was significantly reduced post-training (p < .01, 63.8 ± 18.3 vs 42.7 ± 18.6 cmH₂O).</p

Clinical characteristics of research participants.

<p>Clinical characteristics of research participants.</p

Summary of sexual function data.

<p>Sexual function domain scores for desire and satisfaction (total score from two 5 point questions). Group means are provided in the bottom histogram. Whereas scores for desire significantly increased post-training (*, p = .04), overall satisfaction remained unchanged. Note that scores above the two point minimum for satisfaction were given when research participants reported engagement in sexual activity.</p

Voiding efficiency data summary.

<p>A comparison of pre- and post-training voiding efficiency (VE) values in the eight research participants. While the majority of participants demonstrated an improvement in VE, participant C42 did not have a leak/void and participant A60 just leaked a few drops. When considering the six research participants that had a measurable efficiency, a significant improvement in VE values occurred collectively post-training (p = .046; 39.6 ± 15.5% vs 63.9 ± 8.9%).</p

Bowel items from international SCI data set [75, 76].

<p>Bowel items from international SCI data set [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190998#pone.0190998.ref075" target="_blank">75</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190998#pone.0190998.ref076" target="_blank">76</a>].</p