Emerging Perspectives on Chronic Pelvic Pain and Sexual Health
By Jandra Mueller, DPT, MS, PHRC Encinitas
Last fall (2024), I attended a mast cell conference where my colleague Alyssa Yee, MD and I were invited to speak about the topic of pelvic pain conditions and the role of mast cells; specifically on the topic of endometriosis and neuroproliferative vestibulodynia (NPV) – a specific type of vestibulodynia characterized by excessive nerve endings and mast cells. Over the last few years, sexual medicine and pelvic health providers have been hard at work researching the involvement mast cells play in some of these more difficult, and very painful conditions causing debilitating pelvic pain and sexual dysfunction.
If you’re one of the many individuals dealing with chronic pelvic pain, painful periods, or discomfort with intimacy, you’re not alone—and you’re not imagining it. These symptoms are common, but they’re often misunderstood, misdiagnosed, or minimized. New research and clinical observations are shedding light on an overlooked contributor to this pain: mast cells.
In this blog, we’ll explore what mast cells are, how they relate to conditions like endometriosis and vestibulodynia, and why understanding their role could be the key to better diagnosis and treatment for many people, and ultimately, better treatment options.
What Are Mast Cells?
Mast cells are part of your immune system. Mast cells are commonly found in tissues that have exposure to the outside environment like the respiratory system, the gut, the genitourinary tract, our skin, and our connective tissue. When a substance comes into contact with a mast cell, the mast cell may be triggered and release a variety of substances like histamine, leukotrienes, and tryptase (and many, many more) in response to these triggers. Most people associate them with allergies, but recent findings show that mast cells can also play a role in chronic inflammation, pain, and even tissue remodeling.
What is Mast Cell Activation Syndrome?
Mast cell activation syndrome is a condition where mast cells become over reactive and inappropriately release too many of their mediators (often inflammatory) and typically involve a wide range of symptoms and typically involve multiple body systems. This syndrome was defined and distinguished from a more rare condition, mastocytosis (increased number of mast cells) and allergic reactions.
Mast Cells and the Body Systems They Affect
A very thorough article by Dr. Lawrence Afrin and colleagues (2020) reviewed the diagnosis of MCAS, and we’ve summarized various symptoms specific to each body system below. Mast cell activation syndrome (MCAS) can affect nearly every organ system in the body. Chronic activation of mast cells results in a wide range of symptoms, making the condition hard to identify. Here are some of the key systems impacted:
- Skin: Flushing, itching, rashes, dermatographism (skin writing), and hives.
- Eyes: Irritated or often dry eyes, episodic difficulty focusing, lid tremors/tic
- Gastrointestinal: Nausea, abdominal pain, bloating, reflux, constipation, or diarrhea.
- Genitourinary: Bladder pain, urinary frequency, interstitial cystitis, vaginal pain (vulvodynia), and menstrual irregularities.
- Neurological: Headaches, dizziness, nerve pain, brain fog, memory issues, and sensory hypersensitivities.
- Cardiovascular: Heart palpitations, blood pressure swings, and lightheadedness or fainting.
- Respiratory: Shortness of breath, wheezing, cough, and sinus congestion.
- Musculoskeletal/Connective tissue: Muscle and joint pain, hypermobility (especially in conditions like Ehlers-Danlos Syndrome).
- Endocrine and Immune: Hormonal imbalances, thyroid dysfunction, and increased susceptibility to allergies and infections, hypersensitivity reactions, impaired healing
Understanding this broad impact helps explain why so many patients experience a long diagnostic journey—MCAS often mimics or overlaps with many other disorders.
Mast Cells, MCAS, and Pelvic Pain
Many people with chronic pelvic pain have conditions such as endometriosis, irritable bowel syndrome (IBS), vulvodynia, or painful sex (dyspareunia). While each of these conditions has its own unique features, what they often have in common is inflammation (and pelvic floor dysfunction!)—and for some people, mast cells may be a key factor in driving this inflammation.
A few years ago, Dr. Paul Yong, a sexual medicine OBGYN and researcher, presented a novel concept: Neuroproliferative Dyspareunia. Based on his research, he compared endometriosis and neuroproliferative vestibulodynia, demonstrating similarities in demographics, inflammatory factors, and the role of mast cells. In addition to the work of Dr. Irwin Goldstein and colleagues in NPV pathology over the last few years, along with many of us seeing individuals presenting with both endometriosis and NPV, further research to support Dr. Yong’s theory has begun; looking at both the pathology of the endometriosis lesions and vestibule in individuals with both conditions.
Let’s break it down with two key conditions where mast cells are now being studied more closely: endometriosis and vestibulodynia.
Endometriosis and Mast Cells
Endometriosis is a condition where tissue similar to the lining of the uterus grows on tissues and organs throughout the abdominopelvic cavity as well as distant sites throughout the body. These lesions have many different appearances, are often innervated, and respond to hormones which lead to inflammation, scarring, and pain.
A study by McCallion et al. (2022) demonstrates that endometriosis lesions can actually attract mast cells. These mast cells then release inflammatory substances that contribute to the pain and worsen the disease. In fact, mast cells and estrogen appear to work together, creating an environment that supports ongoing inflammation and nerve growth—both major sources of pain.
This means treatments that only target hormones (like birth control) might miss a key piece of the puzzle. Addressing immune and inflammatory responses, including mast cell activity, could offer new relief.
Vestibulodynia and Mast Cells
Vestibulodynia is simply defined as pain at the entrance of the vagina, often described as burning, stinging, or sharp discomfort, especially with touch, tampon use, or intercourse. Many people are told “nothing is wrong” or are misdiagnosed for years.
There are several causes and associated factors related to vestibulodynia, often related to a reduction in hormones from the use of birth control pills or certain stages of life such as menopause and breastfeeding. Another type is neuroproliferative vestibulodynia, either lifelong or acquired, that does not necessarily involve hormones. Neuroproliferative vestibulodynia is characterized by:
- Higher nerve density in the vulvar tissue (more nerves = more pain signals).
- Increased mast cells in the tissue, contributing to both inflammation and nerve growth.
This is not psychological—it’s a real biological process that can be seen under a microscope.
Why It Matters: A New Way to Look at Old Problems
Traditionally, pelvic pain has been explained through hysteria, psychological blocks, trauma, hormones or mechanical issues. Patients were often told to ‘it’s all in your head’ or to just manage their pain with birth control, surgery, or even a hysterectomy. While there may be a role for some of these interventions in certain cases, they don’t address the underlying immune system activity—like the involvement of mast cells.
By understanding that mast cells are active in both endometriosis and vestibulodynia, along with a wide range of symptoms in patients with chronic pelvic pain, our hope is that more research results in more understanding and more treatment options.
Chronic pelvic pain is rarely caused by a single issue. It often involves the immune system, neuromuscular system, hormones, and emotional well-being. That’s why the best care usually includes a team approach and persistence.
How PHRC and Pelvic Floor Physical Therapy Can Help with Mast Cell-Mediated Pelvic Pain
If you’ve been dealing with ongoing pelvic pain, painful sex, bladder discomfort, or vulvar burning, and haven’t gotten clear answers, you’re not alone. At the Pelvic Health and Rehabilitation Center (PHRC), we specialize in helping people with complex pelvic pain.
Pelvic floor physical therapy (PFPT) is more than just exercise, it’s hands-on, expert care for the muscles, nerves, and tissues of the pelvic region. At PHRC, we’re trained to understand how all of these pieces are connected and interact to cause pain and disrupt your life. Conditions that are mediated or impacted by mast cells aren’t new to us, but our understanding of the condition is constantly evolving.
Our work focuses on:
- Manual therapy directed towards restrictions in the fascial and muscular system impacting the pelvic floor
- Calming down overactive nerves and reducing pain signals
- Improving blood flow and tissue healing
- Teaching you how to manage flares and avoid triggers
- Addressing posture and movement patterns that may be worsening symptoms
- Collaborating with your other healthcare providers (like pelvic pain specialists, allergists, or endometriosis surgeons)
Our evaluations and follow-up sessions are an hour long, one-on-one with an actual physical therapist – no aides or assistants, and very comprehensive.
Our therapists are very familiar with the very complex cases and diagnoses, not only are we trained to help address the myofascial implications, we can help screen for, and direct you, to the various professionals that can help with medical management.
Even if your condition hasn’t been formally diagnosed, we can help you start feeling better through targeted pelvic floor therapy and whole-body strategies; we will also help to facilitate the appropriate referrals and can provide helpful resources. We understand that seeing provider after provider is overwhelming and exhausting. We work with an extensive network of specialists and can help you navigate this journey, get a proper diagnosis, and an effective treatment plan.
If you’ve been struggling with pelvic pain, painful sex, or unrelenting vulvar discomfort and haven’t found relief, don’t give up. There is growing awareness and research into mast cell-mediated pain, and perhaps mast cells will be a key factor in managing some of these more complex conditions. We understand and we can help. At the Pelvic Health and Rehabilitation Center, we offer both in-person physical therapy in the Bay Area, Southern California, and New England, as well as virtual consults. If you are struggling with finding help, please reach out or visit our website for more information.
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Check out our recently published e-book titled “Vulvodynia, Vestibulodynia, and Vaginismus,” designed to empower and inform individuals on their journey towards healing and understanding.
Are you unable to come see us in person in the Bay Area, Southern California or New England? We offer virtual physical therapy appointments too!
Virtual sessions are available with PHRC pelvic floor physical therapists via our video platform, Zoom, or via phone. For more information and to schedule, please visit our digital healthcare page.
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tags: immune cells, mast cell mediators, blood vessels, mature mast cells, other immune cells,