Injury to peripheral or spinal nerves following either
trauma or disease has several consequences including the development of
neuropathic pain. This syndrome is often refractory against conventional
analgesics; and thus, novel medicaments are desired for its treatment. Recent studies have emphasized that dysfunction of inhibitory neuronal regulation of
pain signal transduction may be relevant to the development of
neuropathic pain. Glycinergic neurons are localized in specific brain regions and the spinal cord, where they play an important role in the prevention of pathological
pain symptoms. Thus, an enhancement of glycinergic control in the spinal cord is a promising strategy for
pain relief from
neuropathic pain.
Glycine transporter (GlyT) 1 and GlyT2, which are located in glial cells and neurons, respectively play important roles by clearing synaptically released
glycine or supplying
glycine to glycinergic neurons to regulate glycinergic neurotransmission. Thus, an inhibition of GlyTs could be used to modify
pain signal transmission in the spinal cord. Recently developed specific inhibitors of GlyTs have made this possibility a reality. Both GlyT1 and GlyT2 inhibitors produced potential anti-nociceptive effect in various
neuropathic pain models, chronic and acute inflammatory models in animals. Their anti-
allodynia effects are mediated by the inhibition of GlyTs following activation of spinal
glycine receptor alpha3. These results established GlyTs as target molecules for medicaments for
neuropathic pain. Moreover, the phase-dependent anti-
allodynia effects of GlyT inhibitors have provided important information on effective therapeutic strategies and also understanding the underlying molecular mechanisms of the development of
neuropathic pain.