Learning to promote recovery after spinal cord injury

Abstract

The present review explores the concept of learning within the context of neurorehabilitation after spinal cord injury (SCI). The aim of physical therapy and neurorehabilitation is to bring about a lasting change in function-to encourage learning. Traditionally, it was assumed that the adult spinal cord is hardwired-immutable and incapable of learning. Research has shown that neurons within the lower (lumbosacral) spinal cord can support learning after communication with the brain has been disrupted by means of a thoracic transection. Noxious stimulation can sensitize nociceptive circuits within the spinal cord, engaging signal pathways analogous to those implicated in brain-dependent learning and memory. After a spinal contusion injury, pain input can fuel hemorrhage, increase the area of tissue loss (secondary injury), and undermine long-term recovery. Neurons within the spinal cord are sensitive to environmental relations. This learning has a metaplastic effect that counters neural over-excitation and promotes adaptive learning through an up-regulation of brain-derived neurotrophic factor (BDNF). Exposure to rhythmic stimulation, treadmill training, and cycling also enhances the expression of BDNF and counters the development of nociceptive sensitization. SCI appears to enable plastic potential within the spinal cord by down-regulating the Cl^- co-transporter KCC2, which reduces GABAergic inhibition. This enables learning, but also fuels over-excitation and nociceptive sensitization. Pairing epidural stimulation with activation of motor pathways also promotes recovery after SCI. Stimulating motoneurons in response to activity within the motor cortex, or a targeted muscle, has a similar effect. It is suggested that a neurofunctionalist approach can foster the discovery of processes that impact spinal function and how they may be harnessed to foster recovery after SCI.

Keywords: BDNF; GABA; Ionic plasticity; Metaplasticity; Neurofunctionalism; Nociception; Pain; Relational learning; Sensitization; Timing.