Fig. 3

Macrophage and nerve fiber interaction contributes to inflammatory response and hypersensitivity in endometriosis. NE from decreased sympathetic nerve fibers binds the β2 receptor on macrophages and then activates the PKA signaling leading to the increased TNF-α from macrophages and therefore regulating the inflammatory response. SP released from sensory nerve fibers stimulates the macrophage to release pro-inflammatory cytokines. TNF-α and MCP-1 secreted from macrophages bind to SCNA and TRPV1 on the surface of the neuron. This process enhances the currents in the nerve fibers and leads to hypersensitivity and hyperalgesia. Both inflammation and hypersensitivity in the endometriotic lesion contribute to the generation of pain sensation. NE: norepinephrine; TNF-α: tumor necrosis factor alpha; SP: substance P; MCP-1: monocyte chemoattractant protein 1; SCNA: sodium channel protein; TRPV1: transient receptor potential vanilloid 1