Astrocytes--multitaskers in chronic pain

Treatment of chronic pain remains a clinical challenge and sufficient pharmacological management is difficult to achieve without concurrent adverse drug effects. Recently the concept of chronic pain as a solely neuron-mediated phenomenon has evolved and it is now appreciated that also glial cells are of critical importance in pain generation and modulation. Astrocytes are macroglial cells that have close structural relationships with neurons; they contact neuronal somata and dendrites and enwrap synapses, where small astrocytic processes have been shown to be highly motile. This organization allows astrocytes to directly influence and coordinate neurons located within their structural domains. Moreover, astrocytes form astroglial networks and calcium wave propagations can spread through neighbouring astrocytes. ATP, which is released from astrocytes in response to elevated intracellular calcium concentrations, can contribute to the central mechanisms in chronic pain via purinergic receptors. In this review we highlight the structural organization and the functionalities of astrocytes that allow them to undertake critical roles in pain processing and we stress the possibility that astrocytes contribute to chronic pain not via a single pathway, but by undertaking various roles depending on the pain condition.