title: 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.
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California , San Francisco, California.
authors.forename: J Russell
authors.initials: JR
authors.lastname: Huie
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California , San Francisco, California.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Morioka
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California , San Francisco, California.
authors.forename: Jenny
authors.initials: J
authors.lastname: Haefeli
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California , San Francisco, California.|2 San Francisco Veterans Affairs Medical Center , San Francisco, California.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D007155:Immunologic Factors
keywords: neuroplasticity; recovery; rehabilitation; spinal cord injury