[The mechanism and control of neuropathic pain].
Neuropathic pain is a debilitating pain that occurs after nerve injury and is generally resistant to currently available treatments including morphine. Such pain involves aberrant excitability in dorsal horn neurons after nerve injury. Emerging evidence indicate that the enhanced activity of dorsal horn neurons requires a communication with microglia. Results of our laboratory have shown that activating P2X4R upregulated in spinal microglia after nerve injury contributes to neuropathic pain through a release of BDNF from microglia, which is a crucial factor to signal to dorsal horn neurons to cause neuronal hyperexcitability. Activated spinal microglia also express P2Y12R, and P2Y12R-KO mice display impaired neuropathic pain. The mechanisms of microglia activation are unknown, but our recent study shows that interferon-gamma (IFN-gamma) can be an important factor that causes spinal microglia activation after nerve injury. IFN-beta upregulates P2X4R in microglia and causes P2X4R-dependent allodynia. These findings suggest that purinoceptors in spinal microglia is crucial for pathological intractable pain.
Inoue
Kazuhide
K
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University.
D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D016623:Ion Pumps / Q000502:physiology; D017628:Microglia / Q000378:metabolism* / Q000502:physiology; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology*; D010812:Physical Stimulation; D018048:Receptors, Purinergic P2 / Q000378:metabolism* / Q000502:physiology; D058848:Receptors, Purinergic P2X4; D058925:Receptors, Purinergic P2Y12; D013116:Spinal Cord; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D016623:Ion Pumps; C548226:P2RX4 protein, human; C548576:P2RY12 protein, human; C548227:P2rx4 protein, mouse; C548577:P2ry12 protein, mouse; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D058925:Receptors, Purinergic P2Y12; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; D007371:Interferon-gamma