Neuropathic pain resulting from nerve injury or from diseases such as diabetes, HIV
AIDS or
cancer, that damage the peripheral nerves, can be agonizing, persistent over long periods, and, unfortunately, is often resistant to known
pain-killers. The P2X receptors, of which seven subtypes (P2X1-P2X7) have been cloned, are a family of
ligand-gated
cation channels activated by extracellular
ATP and have important roles in regulating neuronal and glial functions in the nervous system. Recent advances in our understanding of the mechanisms underlying
neuropathic pain have been made by defining important roles of P2X4 receptors and spinal microglia in the pathogenesis of
neuropathic pain. Within the spinal dorsal horn,
peripheral nerve injury leads to a progressive series of changes in microglia including morphological
hypertrophy of the cell body and proliferation that are considered indicative of activation. Furthermore, P2X4 receptors that which are upregulated in activated microglia, have been found to be essential molecular mediators. The activation of P2X4 receptors releases
brain-derived neurotrophic factor from microglia; this mediates the signaling from microglia to neurons, which in turn leads to
pain hypersensitivity. We expect that understanding the key roles of these molecules in spinal microglia may lead to new strategies for the management of
neuropathic pain.