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Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

FRONTIERS IN PHYSIOLOGY (2012)

Journal

FRONTIERS IN PHYSIOLOGY

Volume 3, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA

DOI: 10.3389/fphys.2012.00399

Keywords

pain; nociception; plasticity; spinal cord injury; spinal cord learning; recovery of function

Funding

National Institute of Neurological Disorders and Stroke [NS063597, NS067092, NS041548]
National Institute of Child Health and Development [HD058412]

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Abstract

Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI.

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Activity-dependent plasticity and spinal cord stimulation for motor recovery following spinal cord injury

Soshi Samejima, Richard Henderson, Jared Pradarelli, Sarah E. Mondello, Chet T. Moritz

Summary: Spinal cord injuries often result in permanent physical impairments despite being incomplete disruptions. However, remaining connections between the brain and spinal cord can induce neural plasticity to improve sensorimotor function, even years post-injury. This review provides an overview of evidence for motor recovery, plasticity, and interventions in spinal cord stimulation for motor control restoration. It discusses both open-loop and closed-loop stimulation approaches, as well as mechanisms of spinal cord neuromodulation for sensorimotor recovery, aiming to advance rehabilitation for spinal cord injuries.

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