Endometriosis is a condition where tissue similar to the lining of the uterus, known as the endometrium, grows outside the uterine cavity. These growths, or lesions, are most often found in the pelvic region, including the ovaries, fallopian tubes, and the outer surfaces of the uterus and bladder. The hallmark symptom that drives patients to seek help is severe, often chronic pain. This pain is complex and multifactorial, stemming from a combination of chemical irritation, nerve changes, and structural damage within the pelvic cavity.
Inflammation and Chemical Irritation
The ectopic tissue found outside the uterus still responds to the body’s hormonal cycle, specifically to estrogen. During the menstrual cycle, this tissue attempts to thicken and then shed, just like the normal uterine lining. Since the lesions are trapped inside the body, the resulting blood and tissue debris have no way to exit, leading to localized internal bleeding and breakdown in the pelvic cavity.
This internal event triggers an intense inflammatory response from the immune system. The lesions and nearby immune cells release inflammatory mediators, including prostaglandins, interleukins, and tumor necrosis factor (TNF-α). These chemicals directly irritate the surrounding tissues and nerve endings, causing acute and cyclical pain, known as dysmenorrhea. Prostaglandin E2, in particular, is elevated and is a powerful pain-sensitizing molecule that drives severe cramping and heightened pain perception.
The continuous presence of this inflammatory fluid creates a hostile environment that perpetuates chronic irritation. Estrogen further amplifies this process by promoting the release of more inflammatory cytokines. This chemical environment not only causes pain but also contributes to the growth and persistence of the lesions themselves.
Nerve Growth and Hypersensitivity
Beyond chemical irritation, the lesions actively interact with the nervous system. Endometriosis lesions stimulate the growth of new nerve fibers, a process called neurogenesis, making the lesions themselves highly innervated and sensitive. The lesions produce high levels of neurotrophic factors, such as Nerve Growth Factor (NGF), which recruit sensory and sympathetic nerve fibers to grow directly into the ectopic tissue.
This increased density of nerve fibers means that the lesions send more pain signals to the spinal cord and brain. This constant barrage of signals can lead to peripheral sensitization, where the nerve endings at the site of the lesion become hyper-responsive to even minor stimuli. The pelvic region becomes overly sensitive, causing disproportionate pain.
Furthermore, the chronic pain input leads to central sensitization, which “rewires” the nervous system. The spinal cord and brain become persistently hyper-excitable, essentially turning up the volume on all pain signals. This means that the central nervous system continues to perceive pain severely, resulting in chronic pelvic pain that persists outside of the menstrual cycle and can include painful responses to non-painful stimuli (allodynia).
Structural Damage and Adhesions
The repeated cycles of bleeding, inflammation, and healing in the pelvis cause structural changes. The body’s attempt to repair the inflamed areas leads to the formation of scar tissue, a process known as fibrosis. These bands of scar tissue, called adhesions, bind organs together that are normally separate and mobile.
Adhesions can attach the uterus to the bowel or the ovaries to the pelvic sidewall. When a person moves, digests food, or undergoes their menstrual cycle, these stuck organs are pulled and stretched by the inflexible scar tissue. This mechanical tethering causes chronic, non-cyclical pain, often described as a sharp, pulling, or tugging sensation.
In severe cases, extensive scar tissue can cause a “frozen pelvis,” where the organs are so densely bound together that their normal function is significantly restricted. This structural restriction is a purely mechanical source of pain. It can cause symptoms like painful intercourse, painful bowel movements, and chronic tension.
Impact of Deep Lesion Location
The location and depth of the endometriotic lesions influence the severity and type of pain. When the tissue infiltrates more than five millimeters deep into the underlying tissue, it is classified as Deep Infiltrating Endometriosis (DIE). These lesions commonly involve the walls of the bowel, the bladder, the uterosacral ligaments, and the pelvic nerves.
The pain is amplified in these locations because the lesions are embedded in organs with high nerve density and functional requirements. For example, DIE on the bowel can cause severe pain with defecation, while lesions on the bladder can lead to painful, frequent urination.
Deep lesions are more likely to involve and compress the large pelvic nerves, a phenomenon known as perineural invasion. This direct involvement of major nerve trunks results in severe neuropathic pain, which can manifest as burning, shooting, or radiating pain into the legs or back. The combination of inflammation, nerve growth, and physical invasion makes DIE debilitating and often correlates with high patient-reported pain scores.