Electrical stimulation for the treatment of spinal cord injuries: A review of the cellular and molecular mechanisms that drive functional improvements

Spinal cord injury (SCI) is a devastating condition that leads to loss of motor, sensory, and autonomic functions, often accompanied by chronic neuropathic pain. Current treatments have limited efficacy, but electrical stimulation has emerged as a promising intervention. Electrical stimulation, including epidural electrical stimulation (EES), peripheral nerve stimulation (PNS), and functional electrical stimulation (FES), has demonstrated improvements in individuals with SCI, ranging from regaining weight-bearing locomotion to recovery of sexual function and neuropathic pain relief. The review explores cellular and molecular mechanisms involved in functional improvements from electrical stimulation, identify gaps in current knowledge and highlight potential research avenues for future studies.

• 1
  Electrical stimulation can induce local neuroplasticity between afferent fibers, interneurons, and motoneurons, resulting in greater motoneuron activation from afferent inputs, improving muscle recruitment.
• 2
  Residual descending pathways exist post-SCI, but they are considered “functionally inactive” and unable to produce meaningful movement without interventions. Electrical stimulation may raise the net excitability of the spinal cord circuitry to facilitate movement.
• 3
  Increased BDNF expression may promote spinal cord remodeling through several signaling pathways. After release, BDNF primarily binds to the TrkB receptor to exert downstream cellular effects.