γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in spinal dorsal horn. GABA activates Cl−-permeable GABAA receptors and G-protein coupled GABAB receptors at synaptic and extra-synaptic sites. GABAergic neurons are numerous in spinal dorsal horn, constituting 30% of the neuron population in laminae I and II where nociceptive nerve fibers terminate. Synaptic transmission from nociceptive nerve fibers to spinal dorsal horn neurons is under permanent and powerful inhibitory control, mainly by neurons that use GABA as a neurotransmitter [1,2,3]. Impaired spinal inhibition may contribute to hyperalgesia and may also lead to touch-evoked pain.
We study transgenic mice which express the green fluorescent protein under the promoter of GAD67, a GABA synthesizing enzyme. Our group has shown that the normal excitatory drive to GABAergic neurons is reduced under conditions of a painful neuropathy. The impaired recruitment of inhibition then causes higher-than-normal excitation of spinal neurons upon painful stimuli. Normal inhibition is indispensable for the orderly processing of sensory information in the spinal cord . We demonstrated that insufficient inhibition leads to a breakdown of functional modality borders in the spinal cord . In this case a weak sensory stimulus that normally causes a touch sensation also gains access to the nociceptive system and excites spinal neurons that are otherwise excited only by noxious stimuli. Thus, when inhibition is impaired the abnormal processing of touch-related and nociceptive information may lead to hyperalgesia and allodynia.