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

Abstract

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. 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. Restoring the inhibitory GABAergic tone and preventing damage-induced excitotoxicity by employing various strategies provide neuroprotective and analgesic effects. 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. Taking background knowledge of GABAergic analgesia and recent advancements, we aim to highlight how far we have reached in promoting inhibitory GABAergic tone for SCI-CNP and spasticity.