Figure 2: Schematic of primary afferent releasing factors that are responsible for microglial activation. Microglial cells are activated by factors released from hyperexcitable primary afferents such as CCL2 (MCP-1), ATP, and CX3CL1 (fractalkine). Respective activation of CCR2, P2X4/P2X7, and CX3CR1 receptors on microglia causes phosphorylation of p38 in microglia, leading to increased synthesis and release of TNFα, IL-1β, and BDNF.