FIGURE 1.

Schematic overview of an enhanced immune response leading to chronic pelvic pain in endometriosis. Endometrial fragments in the peritoneum, originating from the uterus during retrograde menstruation, lead to the production and build-up of iron, reactive oxygen species (ROS), prostaglandins (PGE₂) and acidosis in the peritoneal fluid (peritoneal inflammation). This immune response is also seen at lesions sites throughout the peritoneal cavity, where the increased production of cytokines, chemokines, growth factors and neutrophils also contribute to an enhanced inflammatory environment present in the peritoneal cavity of women with endometriosis (lesion inflammation). Of these inflammatory mediators, PGE₂, tumor necrosis factor α (TNFα), nerve growth factor (NGF), RANTES and interleukins (IL) IL-8 and IL-1β are able to directly activate sensory nerve endings and activate a positive feedback loop, further increasing proinflammatory modulator production (neurogenic inflammation). The enhanced stimulation and activation of peripheral nerve endings in the peritoneal cavity (peripheral sensitization) increases the painful stimuli transmitted to the spinal cord, initiating and maintaining chronic pelvic pain (central sensitization).