USC team explores the nervous-system pathways that heighten endometriosis pain

In women and girls with endometriosis, tissue usually found in the lining of the uterus grows where it shouldn’t — on the ovaries, bladder or intestines. The resulting pain, heavy bleeding, exhaustion and emotional toll can upend every part of life, from school and work to relationships. The World Health Organization considers it a significant global health issue, affecting roughly 190 million women and girls worldwide, and a major cause of infertility. Even so, the condition has been largely overlooked until recently, and therefore, poorly understood.

At USC, two researchers — Jason Kutch, who studies chronic pelvic pain, and Neda Jahanshad, an expert in neuroimaging — are collaborating on a project to provide greater clarity on the condition and treatments. They recently won a $3 million grant from the National Institutes of Health to look at pain pathways in the brain to better understand which patients respond to treatment for endometriosis, who doesn’t, and why.

USC News sat down to talk about the project with Kutch, an associate professor in the USC Division of Biokinesiology and Physical Therapy, and Jahanshad, associate professor of neurology and biomedical engineering at the Keck School of Medicine of USC and part of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute.

Endometriosis is usually treated either through surgery or hormonal therapy. But that doesn’t always help, correct?

Kutch: About 25% to 40% of patients don’t get sustained relief from those interventions. That leads many people to undergo multiple surgeries with only limited success.

What’s interesting is that there’s often a limited correlation between how much endometrial tissue is present and how much pain someone feels. Some people with extensive lesions report little pain, while others with minimal visible disease experience extreme pain. It’s a real puzzle.

In this project, you’re focusing on brain imaging data, rather than tissue in the pelvic region. What are you looking for?

Kutch: There’s growing recognition that chronic pain involves a complex interplay between biological pain drivers and how the nervous system detects and interprets those signals. One key concept is central sensitization, where the nervous system becomes overactive and amplifies pain.

In this project, we’re trying to understand that component better: Can we predict who will respond to surgical or hormonal treatment, and who may not?

This builds on my past 14 years studying general pelvic pain — bladder pain, prostate pain and other related conditions — where we’ve seen brain markers that suggest this central sensitization process. The pain experience is far more complicated than just what’s happening in the body.

Jahanshad: This study brings together several independently collected datasets to explore various aspects of pelvic pain and endometriosis, including data from individuals who have undergone treatment. My team specializes in merging different types of data that were collected independently and finding ways to harmonize them.

The goal is to see whether there are brain signatures — before treatment — that can help predict who will respond successfully. We often see that some patients experience pain relapse after treatment or have coexisting conditions such as depression or anxiety that may influence their pain outcomes. We are looking to build a model that can help optimize treatment plans for women with endometriosis.

People often feel dismissed when told their pain is “in their head.” But what you’re saying is that aspects of pain processing literally are in the brain — and understanding that could help.

Kutch: Exactly. The goal is to understand the relative contributions — the body and the brain. Peripheral treatments (aimed at the tissues or organs where the pain originates) remain crucial, but sometimes they need to be paired with approaches that help the nervous system rewire how it processes pain.

Jahanshad: Yes, there are detectable biological differences in the brain that can contribute to pain processing, and we will be trying to define the role of specific structural and functional brain patterns in this process. Female brain health has been very understudied, so this is all very new and exciting work!

If you identify definite abnormalities in pain processing, are there interventions that could help?

Kutch: There are several possibilities. I’m completing a clinical trial using noninvasive brain stimulation in women with interstitial cystitis, a related bladder pain condition, so neuromodulation may ultimately play a role.

There are also centrally acting medications that might be more effective if we can identify the patients whose neural mechanisms make them the most likely to benefit.

And for those who want them, there are supportive strategies that can help reduce nervous-system sensitization — not as a substitute for medical treatment, but as adjuncts that may help some individuals feel a bit more in control of their symptoms.

The best interventions will probably combine different strategies, depending on the severity of the brain’s pain remodeling.