Neuropathic pain and spinal microglia: a big problem from molecules in "small" glia.
Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Such pain can be experienced after nerve injury or as part of diseases that affect peripheral nerve function, such as diabetes and AIDS; it can also be a component of pain in other conditions, such as cancer. Following peripheral nerve injury, microglia in the spinal cord become activated. Recent evidence indicates that activated microglia are key cellular intermediaries in the pathogenesis of nerve injury-induced pain hypersensitivity because P2X(4) purinoceptors and p38 mitogen-activated protein kinase, which are present in activated microglia, are required molecular mediators. It is important to establish how these molecules are activated in spinal microglia following nerve injury and how they cause signaling to neurons in the dorsal horn pain transmission network. Answers to these questions could lead to new strategies that assist in the diagnosis and management of neuropathic pain--strategies not previously anticipated by a neuron-centric view of pain plasticity in the dorsal horn.
Tsuda
Makoto
M
Division of Biosignaling, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
Inoue
Kazuhide
K
Salter
Michael W
MW
D000818:Animals; D006801:Humans; D017628:Microglia / Q000502:physiology*; D008954:Models, Biological; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000378:metabolism*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058848:Receptors, Purinergic P2X4; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C515334:CCR2 protein, human; C548226:P2RX4 protein, human; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D048051:p38 Mitogen-Activated Protein Kinases