The major cellular contributors of chronic pain states and their interface with the microvasculature, including neurons, microglia, astrocytes, perivascular microglia and T-leukocytes are illustrated. Potential drug targets to modulate glial-neuronal function include: (1) inhibiting microglial proliferation and migration, (2) enhancing astrocytic GLT-1 expression, (3) enhancing perivascular ED2/CD163 expression, and (4) interfering with specific neuronal-glial and/or neuronal-immune interactions.