Neuropathic pain is caused by lesion or dysfunction of the peripheral sensory nervous system. Up-regulation of the voltage-gated Ca2+ channel subunit α2δ-1 in DRG (dorsal root ganglion) neurons and the spinal cord correlates with the onset of neuropathic pain symptoms such as allodynia in several animal models of neuropathic pain. The clinically important anti-allodynic drugs gabapentin and pregabalin are α2δ-1 ligands, but how these drugs alleviate neuropathic pain is poorly understood. In the present paper, we review recent advances in our understanding of their molecular mechanisms.

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