Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain

Pathological pain is caused by abnormal activity in the neural circuit that transmits nociceptive stimuli. Beyond homeostatic functions, astrocytes actively participate in regulating synaptic transmission as members of tripartite synapses. The perisynaptic astrocytic process (PAP) is the key structure that allows astrocytes to play these roles and not only physically supports synapse formation through cell adhesion molecules (CAMs) but also regulates the efficiency of chemical signaling. Accumulating evidence has revealed that spinal astrocytes are involved in pathological pain by modulating the efficacy of neurotransmitters such as glutamate and GABA through transporters located in the PAP and by directly regulating synaptic transmission through various gliotransmitters. Although various CAMs contribute to pathological pain, insufficient evidence is available as to whether astrocytic CAMs also have this role. Therefore, more in-depth research is needed on how pathological pain is induced and maintained by astrocytes, especially in the PAP surrounding the synapse, and this will subsequently increase our understanding and treatment of pathological pain.