Spinal Cord Injury Provoked Neuropathic Pain and Spasticity, and Their GABAergic Connection

Traumatic spinal cord injury (SCI) is the devastating neurological damage to the spinal cord that becomes more complicated in the secondary phase. The secondary injury comes with inevitable long-lasting complications, such as chronic neuropathic pain (CNP) and spastic­ity which interfere with day to day activities of SCI patients. Mechanisms underlying CNP post-SCI are complex and remain refractory to current medical treatment. Due to the dam­age, extensive inhibitory, excitatory tone dysregulation causes maladaptive synaptic trans­missions, further altering the nociceptive and nonnociceptive pathways. The present article will discuss CNP and spasticity post-SCI, understanding their pathophysiological mechanisms, especially GABA-glutamate-related mechanisms, therapeutic interventions targeting them, and progress regarding how regulating the excit­atory-inhibitory tone may lead to more targeted treatments for these distressing complica­tions.

• 1
  Excitotoxicity me­diated GABAergic cell loss, downregulation of glutamate acid decarboxylase enzyme, up­regulation of gamma-aminobutyric acid (GABA) transporters, overactivation of glutamate receptors are some of the key evidence for hypoactive inhibitory tone contributing to CNP and spasticity post-SCI.
• 2
  Restoring the inhibitory GABAergic tone and preventing damage-induced excitotoxicity by employing various strategies provide neuroprotective and analge­sic effects.
• 3
  Various reports provide evidence of hypo­active GABAergic inhibition post-SCI as a major cause of spas­ticity development.