Spinal Astrocytes in Pain Processing: Non-Neuronal Cells as Therapeutic Targets

Topographical interrelationships among astrocytes, microglia, and neurons in the CNS. Astrocytes (green) interact with a number of elements: i) capillaries (red; the typical astrocyte endfoot–vessel interaction is indicated); ii) neurons and synapses (blue), thereby giving rise to tripartite synapses; and iii) other astrocytes via gap junctions that permit calcium waves to spread over long distances in the astrocyte network. Astrocytes may release a number of “gliotransmitters” at the tripartite synapses or directly into the extracellular space. Increasing evidence indicates that microglial cells (white) may also be a part of the functional unit of the synapse (thereby constituting a tetrapartite synapse as indicated at bottom of figure). Glial cells are depicted in their resting state. (Oligodendrocytes, which constitute the third major class of glia, are not shown).