Endometriosis Is a Nervous System Disease

I had my first excision surgery at 24. Two expert surgeons. Lesions everywhere — rectum, bladder, peritoneum. They got it all, or so we thought. I remember waking up with this fluttering hope. This is it. I'm fixed. I'm going back to my life.

Three months later, the pain came back. Not the same pain. A different pain. A pain that seemed to exist everywhere and nowhere at once. A pain that didn't match my imaging anymore. A pain that made me wonder if I was losing my mind.

I wasn't. My nervous system was just learning.

This is the piece of endometriosis that almost nobody talks about, and it's the piece that changed everything about how I practice. Endometriosis isn't just a disease of the pelvis. After years of signaling danger to your brain, it becomes a disease of your nervous system. Your brain learns that your pelvis is a threat. And once the brain learns something, the pain persists even when the original threat is gone.

Central Sensitization: The Alarm System That Won't Reset

In one study of endometriosis patients, 41.4% showed evidence of central sensitization. That's nearly half. Central sensitization is when your nervous system gets stuck in a state of amplified pain perception. The smoke detector in your house doesn't just go off when there's a fire anymore — it goes off at the smell of toast.

Here's what happens physiologically: chronic pain sends repeated signals to your spinal cord and brain. Pain neurotransmitters like glutamate and substance P flood the synapses. The system becomes hyperexcitable. The threshold for pain gets lower. A stimulus that used to register as "pressure" now registers as "pain." The brain resets its alarm sensitivity upward.

This is called wind-up. The nervous system literally becomes more responsive to pain signaling. It's not your imagination. It's not psychological. It's a measurable change in nociceptive processing.

And here's what makes it tricky: even after you remove the source of the pain signals — even after surgery removes the lesions — the nervous system doesn't automatically reset. The alarm is still set to "hair-trigger." Your brain remembers that your pelvis was dangerous. It protects you by keeping the pain signal amplified.

Neuroangiogenesis: When Lesions Grow Their Own Nerve Supply

But here's the thing that really matters: it's not just about the brain learning. The lesions themselves are recruiting nerves. This is called neuroangiogenesis — the growth of new blood vessels and nerve fibers into abnormal tissue.

Endometrial lesions produce growth factors like nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). These chemicals are like a beacon to nerve fibers: "Come here. Grow toward me." And the nerve fibers do. They innervate the lesion. They integrate into the abnormal tissue.

The result is that endo lesions become densely innervated. They have far more nerve fibers than normal endometrium. They're not just inflamed — they're wired to send pain signals directly to your spinal cord and brain.

One study found nerve fiber density in endometrial lesions was significantly elevated compared to normal endometrium. Another found that lesion size actually didn't correlate with pain severity, but innervation density did. Meaning the number of nerves in a lesion was a better predictor of pain than the size of the lesion.

This is crucial because it means: removing the lesion doesn't always remove all the nerve fibers. Some of those nerves have already integrated into your pelvic nervous system. They've become part of the local neural architecture. That's why pain can persist.

The Vagus Nerve: Your Built-In Anti-Inflammatory Highway

Now here's where it gets hopeful. Your body has a built-in system to counteract this. It's called the vagal anti-inflammatory pathway, and it's mediated by the vagus nerve — the longest cranial nerve in your body.

The vagus nerve connects your brain directly to your organs. When you stimulate vagal tone — through deep breathing, cold water exposure, gentle movement, certain types of meditation — you trigger the parasympathetic nervous system. That releases acetylcholine, which signals macrophages: "Stand down. This isn't a threat."

In other words, vagal tone is how your brain tells your immune system to stop fighting. When you have chronic inflammation from endometriosis, your vagal tone is often suppressed. You're stuck in a state of sympathetic dominance — fight-or-flight mode. Your nervous system is primed for danger.

But here's what's remarkable: vagal tone can be trained. It's not fixed. You can literally practice activating your parasympathetic system, and over time, the system becomes more responsive. The alarm becomes easier to turn off.

Pain Reprocessing Therapy: Teaching Your Brain to Unlearn

In one landmark study, people with chronic back pain underwent Pain Reprocessing Therapy (PRT). The treatment involved understanding the neuroscience of pain, reconceptualizing the pain as a learned response rather than a threat signal, and gradually reengaging with activities while monitoring for safety.

The results: 66% of participants achieved meaningful pain reduction. Two-thirds. And the changes persisted at follow-up.

I want to be clear: this study was in back pain, not endometriosis-specific. But the mechanism matters. The brain learned pain. The brain can unlearn it. Not by denying the pain or thinking positively about it — by actually understanding how the nervous system works and helping it recalibrate.

This is why a comprehensive approach to endo sometimes involves working with someone trained in pain neuroscience, somatic therapy, or trauma-informed care. Not instead of treating the disease. Alongside it. Because you're treating both the tissue and the nervous system that's learned to protect it.

Neuroplasticity: Your Brain Isn't Fixed

The word that matters here is neuroplasticity. Your nervous system isn't a fixed circuit. It's constantly rewiring itself based on what you do, what you practice, what you pay attention to.

If you've spent ten years sending danger signals to your brain every time you move, your brain wires itself to expect danger with movement. But if you start — gradually, gently — challenging that expectation, the wiring starts to change. New pathways form. The old pathways weaken from disuse.

This doesn't mean "mind over matter." It means understanding that your pain is real, your nervous system's learning is real, and the capacity to reshape that learning is also real.

What This Actually Looks Like

If you've had surgery and your pain persists, asking "Did they get it all?" might be the wrong question. A better question is: "Is my nervous system in a state of central sensitization? Are my lesions heavily innervated? Is my vagal tone suppressed?"

Those questions lead to different treatment strategies. Addressing central sensitization might mean working with someone trained in pain science, neuroscience-informed therapy, or somatic practice. Improving vagal tone might mean specific breathwork or gentle nervous system interventions. Reducing ongoing inflammation — even subclinical inflammation — still matters, because it's still sending signals to your brain.

And here's the thing that gets me emotional when I think about it: your brain is plastic. Capable of change. This doesn't mean your pain is your fault. But it does mean it's not permanent. You're not stuck with the alarm setting your nervous system learned.

You can teach it something different.

Heather Yoshimura, MSN, AGNP-BC

UCSF-trained nurse practitioner specializing in endometriosis. Founder of Luteal Health. Author of The Endo Dilemma.