Spinal glial activation contributes to pathological pain states

Chronic pain, a pathological state, affects millions of people worldwide. Despite decades of study on the neuronal processing of pain, mechanisms underlying the creation and maintenance of enhanced pain states after injury or inflammation remain far from clear. In the last decade, however, the discovery that glial activation amplifies pain has challenged classic neuronal views of "pain". This review focuses on recent developments in understanding that spinal cord glia are involved in pathological pain. We overview the action of spinal glia (both microglia and astrocytes) in several persistent pain models, and provide new evidence that spinal glia activation contributes to the development and maintenance of arthritic pain facilitation. We also attempt to discuss some critical questions, such as how signals are conveyed from primary afferents to spinal glia following peripheral nerve injury and inflammation. What causes glia to become activated after peripheral/central injury/inflammation? And how the activated glia alter neuronal sensitivity and pain processing? Answers to these questions might open a new approach for treatment of pathological pain. (C) 2008 Elsevier Ltd. All rights reserved.