Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain.
When you hurt yourself, you become consciously aware of the pain because a chain of neurons carries the pain message from the injury to the spinal cord, and then from the spinal cord up to consciousness in the brain. However, it has been known for more than two decades that neural circuits within the spinal cord can cause your conscious experience of pain to be amplified-that is, the pain you perceive is out of proportion to the injury that caused it. Until now, all research aimed at understanding how pain amplification occurs in the spinal cord and all drug therapies aimed at curing exaggerated pain have focused exclusively on neurons. This is because neurons were the only type of cell believed to be important in pain. The present review argues that neurons in fact are not the only cell type involved. Rather, that spinal cord cells called "glia" are also critically important. Indeed, when glia become activated, they begin releasing a variety of chemical substances that causes the pain message to become amplified, thus causing pain to hurt more. This review discusses evidence that glia cause pain to become amplified and describes how the glia cause this to happen. The take-home message is that drugs that target glia and the chemical substances that these glia release are predicted to be powerful remedies for pain problems in people.
Watkins
Linda R
LR
Department of Psychology, Center for Neurosciences, University of Colorado at Boulder, USA.
Milligan
Erin D
ED
Maier
Steven F
SF
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000503:physiopathology; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology; D007378:Interleukins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D008959:Models, Neurological; D009457:Neuroglia / Q000378:metabolism*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000503:physiopathology; D013116:Spinal Cord / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha