What Is Being Trained? How Divergent Forms of Plasticity Compete To Shape Locomotor Recovery after Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a devastating syndrome that produces dysfunction in motor and sensory systems, manifesting as chronic paralysis, sensory changes, and pain disorders. The multi-faceted and heterogeneous nature of SCI has made effective rehabilitative strategies challenging. Work over the last 40 years has aimed to overcome these obstacles by harnessing the intrinsic plasticity of the spinal cord to improve functional locomotor recovery. Intensive training after SCI facilitates lower extremity function and has shown promise as a tool for retraining the spinal cord by engaging innate locomotor circuitry in the lumbar cord. As new training paradigms evolve, the importance of appropriate afferent input has emerged as a requirement for adaptive plasticity. The integration of kinematic, sensory, and loading force information must be closely monitored and carefully manipulated to optimize training outcomes. Inappropriate peripheral input may produce lasting maladaptive sensory and motor effects, such as central pain and spasticity. Thus, it is important to closely consider the type of afferent input the injured spinal cord receives. Here we review preclinical and clinical input parameters fostering adaptive plasticity, as well as those producing maladaptive plasticity that may undermine neurorehabilitative efforts. We differentiate between passive (hindlimb unloading [HU], limb immobilization) and active ( peripheral nociception) forms of aberrant input. Furthermore, we discuss the timing of initiating exposure to afferent input after SCI for promoting functional locomotor recovery. We conclude by presenting a candidate rapid synaptic mechanism for maladaptive plasticity after SCI, offering a pharmacological target for restoring the capacity for adaptive spinal plasticity in real time.

Cadence Tracking and Disturbance Rejection in Functional Electrical Stimulation Cycling for Paraplegic Subjects: A Case Study

“…As the subject was under appropriate pharmacological control prescribed by a physician, we supposed that he was exposed to overloaded intensities at the end of the training by which an inappropriate afferent input on spinal cord motor plasticity generated a maladaptive hyper‐excitability response . Our hypothesis is that, at the beginning of the experiment, the low intensities of stimulation and training provided by kinematic and electrical inputs were suitable to modulate the motoneuron excitability preventing spasticity and other involuntary reactions.…”

Ambulation in Dogs With Absent Pain Perception After Acute Thoracolumbar Spinal Cord Injury

“…There is increased importance of the integration between sensory input and CPG activity to coordinate motor output due to limited or lack of supraspinal control (29). Alterations in both motor neuron pool excitability and sensory input to the dorsal horn occur and likely contribute to functional status after injury (38,(58)(59)(60)(61)(62). For example, pharmacologic inhibition of postsynaptic inhibition with strychnine has been used to facilitate spinal walking in experimentally transected dogs (63).…”

“…For example, pharmacologic inhibition of post-synaptic inhibition with strychnine has been used to facilitate spinal walking in experimentally transected dogs ( 63 ). However, maladaptive plasticity and development of aberrant neuronal circuits commonly manifested as neuropathic pain or spasticity can also occur and impair functional recovery ( 58 , 60 ).…”

Inhibition of Nkcc1 promotes axonal growth and motor recovery in ischemic rats

“…Current treatment options for stroke patients are limited. Evidence is emerging to suggest that the brain is able to respond to injury to restore lost functions (Carmichael, 2003;Huie et al, 2017). The repair mechanisms include axonal and dendritic reorganization, altered excitability, neurogenesis and angiogenesis; these processes are activated with a delay, thus opening a wider therapeutic window for treatment.…”