The Purinergic System and Glial Cells: Emerging Costars in Nociception

Figure 1

Central role of microglial P2X4 receptors in mediating a molecular cascade leading to hypersensitivity after peripheral nerve injury (PNI). The upper left cartoon shows the neuron-to-microglia cross talk triggered by neuronal injury, leading to the appearance of an “activated” microglia phenotype, which expresses higher levels of the P2X4 receptor. The dotted rectangle is expanded in the lower panel, showing the complex molecular network responsible for P2X4 receptor upregulation and involving chemokines, growth factors, and integrins. Activation of the P2X4 receptor ultimately leads to the recruitment and activation of p38 MAP kinase. Reproduced from [56] with permission from Nature Publishing Group.