Early Transcutaneous Tibial Nerve Stimulation Acutely Improves Lower Urinary Tract Function in Spinal Cord Injured Rats

Abstract

Despite the fact that a majority of patients with an injury to the spinal cord develop lower urinary tract dysfunction, only few treatment options are available currently once the dysfunction arises. Tibial nerve stimulation has been used in pilot clinical trials, with some promising results. Hence, we investigated whether the early application of transcutaneous tibial nerve stimulation in the animal model of spinal cord injured rats can prevent the development of detrusor overactivity and/or detrusor-sphincter-dyssynergia. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. A dorsal over-hemisection, resulting in an incomplete spinal cord injury at the T8/9 spinal level, induced immediate bladder paralysis. One week later, the animals received daily tibial nerve or sham stimulation for 15 days. Effects of stimulation on the lower urinary tract function were assessed by urodynamic investigation. Measurements showed improvements of several key parameters of lower urinary tract function—in particular, non-voiding bladder contractions and intravesical pressure—immediately after the completion of the stimulation period in the stimulated animals. These differences extinguished one week later, however. In the dorsal horn of the lumbosacral spinal cord, a small significant increase of the density of C-fiber afferents layers I-II was found in the stimulated animals at four weeks after spinal cord injury. Tibial nerve stimulation applied acutely after spinal cord injury in rats had an immediate beneficial effect on lower urinary tract dysfunction; however, the effect was transitory and did not last over time. To achieve more sustainable, longer lasting effects, further studies are needed looking into different stimulation protocols using optimized stimulation parameters, timing, and treatment schedules.

Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury

“…Sacral root stimulation has been used for years to improve micturition in SCI patients; however, is not widely applied due to its complexity. 98 Tibial nerve stimulation has been reported to be effective in treating neuropathic overactive bladder preclinically 99 and clinically. 100 , 101 In addition to promoting motor recovery, epidural stimulation has improved bladder function in several cases.…”

Full regeneration of descending corticotropin-releasing hormone axons after a complete spinal cord injury in lampreys

“…Regeneration of CRH-ir axons occurs in lampreys with a high degree of functional recovery (Ayer’s test) and these regenerated axons not only regrow through the site of injury and for some millimeters caudally, but also re-establish pre-synaptic contacts with targets below the site of injury. In contrast, CRH projections from the Barrington’s nucleus are only partially recovered in lumbosacral levels 4 weeks after an incomplete spinal cord transection at T8/T9 (thoracic level) in rats [40] , which parallels bladder malfunction in these animals. Thus, our work provides a new model to understand spontaneous and successful axonal regeneration in a neurochemically-distinct neuronal population in lampreys, which in the past has mainly relied on the analysis of giant descending neurons by using tracer applications.…”

“…Restoration of urination control is one of the main aims in SCI patient management [39] . Importantly, CRH projections from the Barrington’s nucleus are only minimally recovered in lumbosacral levels 4 weeks after an incomplete spinal cord transection at T8/T9 (thoracic level) in rats [40] . In the spinal cord of mature larval sea lampreys, CRH neurons are only present in the most rostral spinal cord, close the rhombencephalon/spinal cord transition [34] .…”

Integrated Neuroregenerative Techniques for Plasticity of the Injured Spinal Cord

“…Unlike the epidural method, transcutaneous stimulation is a non-invasive approach to spinal cord stimulation, which involves the placement of electrodes onto the surface of the patient’s skin. Furthermore, aside from this approach being less invasive, preliminary studies reported potential benefits in reducing muscle spasticity, improving residual motor functioning, and regulating autonomic functions, including heart rate, thermoregulation, and bladder sphincter function [ 69 , 70 ]. On top of experimental studies on animals, more clinical trials and human studies are needed to fully ascertain the advantages and long-term side effects of spinal cord stimulation for SCI [ 63 ].…”