UC Irvine

Spinal cord injury (SCI) often causes sensitization of spinal dorsal horn excitatory neurons via disruption of inhibitory output that results in exaggerated nociceptive transmission. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter and thought to be critical for spinal inhibitory synaptic transmission. However, SCI causes hypofunctional GABAergic inhibitory output via multiple mechanisms, including loss of GABAergic neurons, downregulation of GABA synthesis enzymes, decrease of primary afferent innervation into GABAergic neurons, and shifts of Cl− gradient in the spinal dorsal horn. These disruptions of GABAergic inhibitory output critically contribute to neuronal hyperexcitability in the spinal dorsal horn and chronic neuropathic pain states following SCI. In this book chapter, we focus on spinal GABAergic mechanisms of chronic neuropathic pain development following SCI in rodent animals.