Development of next-generation
analgesics requires a better understanding of the molecular and cellular mechanisms underlying pathological
pain. Accumulating evidence suggests that the activation of glia contributes to the central sensitization of
pain signaling in the spinal cord. The role of microglia in pathological
pain has been well documented, while that of astrocytes still remains unclear. After peripheral nerve
inflammation or
injury, spinal microglia are initially activated and subsequently sustained activation of astrocytes is precipitated, which are implicated in the induction and maintenance of pathological
pain. Astrocytic activation is caused by the production of diffusible factors from primary afferent neurons (neuron-to-astrocyte signals) and activated microglia (microglia-to-astrocyte signals). Although astrocyte-to-neuron signals implicated in pathological
pain is poorly understood, activated astrocytes, as well as microglia, produce proinflammatory
cytokines and
chemokines, which lead to adaptation of the dorsal horn neurons. Furthermore, it has been suggested that glial
glutamate transporters in the spinal astrocytes are down-regulated in pathological
pain and that up-regulation or functional enhancement of these transporters prevents pathological
pain. This review will briefly discuss novel findings on the role of spinal astrocytes in pathological
pain and their potential as a therapeutic target for novel
analgesics.