Mast Cell Medications: A Potential Key to the Treatment of Chronic Pain

I have recently accepted medical students back into my practice to observe and learn with me. One student asked me if I ever made a mistake in diagnosis and prescribed a mast cell stabilizer medication to someone who did not have mast cell activation syndrome. 

This really made me think, and I realized how much my world has changed since studying the impact that mast cells have on human health. I realized that I have jumped way beyond just mast cell activation syndrome. I like to think about how mast cells relate to all aspects of chronic illness where inflammation is involved, not just with patients who have mast cell activation syndrome. 

Pain is the number one reason why patients seek out medical care.¹ Many of the patients I treat suffer from constant or intermittent pain. As always, I seek the root cause of healthcare concerns. I have found that using mast cell stabilizing medications can relieve the symptoms of pain while also allowing us to better understand what contributes to the symptoms of pain itself. 

Within the last several years, new research has demonstrated the key role that mast cells have in individuals with chronic pain. 

I’m not diagnosing everyone I treat with mast cell activation syndrome – this is a specific clinical diagnosis with unique signs and symptoms. But what I have realized is how much pain has to do with the activation of mast cells. When activated, mast cells work as both innate and acquired immune cells that communicate with the autonomic nervous system to warn the body and the mind of danger. 

It does not matter whether one has mast cell activation syndrome or not; this process occurs in everyone. When mast cells activate, their communication with the autonomic nervous system has the potential to result in pain. 

It is this connection between mast cells and the autonomic nervous system that communicates the perception of pain in many of my patients. When used as an adjunctive therapy, mast cell stabilizers are proven to be effective in the treatment of chronic pain. This is because they work to decrease the release of inflammatory mediators between mast cells and the autonomic nervous system. This is why I continue to recommend mast cell stabilizers for pain even in my patients without mast cell activation syndrome. 

What Are Mast Cells? And What Do They Have to Do With Your Chronic Pain?

Mast cells work with the immune system to act as a first line of defense in the body. While they’re located all over the body, higher amounts of mast cells can be found in areas that are in contact with the external environment. This includes the intestines, airways, and the skin.²

The location of mast cells is what allows them to protect the body. I like to describe mast cells as your own private bouncer for the night club of your immune system. When mast cells become aware of something outside of the body that is potentially harmful, they are activated and release several compounds. This process is called mast cell degranulation.³

One of the main compounds released by mast cells is called histamine. When released, histamine as well as other pro-inflammatory compounds notify nerve endings of potential damage to the body. This signal then gets sent to the brain and can ultimately result in the feeling of pain. 

Research shows that mast cells and nerves have a close, working relationship.⁴ This relationship between mast cells and the nervous system is what causes pain in many of my patients. By decreasing the activity of mast cells with a mast cell stabilizer, pain can be treated. 

Which Mast Cell Stabilizers Treat Chronic Pain?

Mast cell stabilizers treat the pain while we search for the root cause of mast cell activation. Mast cell stabilizers decrease the activation of mast cells which means that less compounds like histamine are released. This results in less stimulation of nearby nerve endings, which means that fewer pain signals are sent to the brain and felt by the body. 

There are several types of mast cell stabilizers that I like to prescribe: Ketotifen, Quercetin, and Urtica dioica.

Ketotifen

One of my favorite pharmaceuticals is called Ketotifen. This is typically my number one choice to try because it is highly effective while also having a low side effect profile. This allows many of my patients to be able to tolerate it well.

Ketotifen belongs to a class of medications called antihistamines, though its antihistamine mechanism is slight compared with other medications in the same class. Ketotifen has been shown to decrease inflammation and pain by inhibiting the release of inflammatory compounds from mast cells.⁵

Although Ketotifen is discussed as being a medication specifically for the treatment of asthma and allergies, I use it all of the time in my patients with pain. Examples of pain that can be treated with ketotifen include:

  • Chronic musculoskeletal and joint pain

  • Pain of the digestive system

  • Chronic headaches and brain fog


The United States is currently the only country that does not have a patented name brand medication with Ketotifen. Luckily, I am able to get Ketotifen for my patients through a compounding pharmacy. This gives me the ability to prescribe Ketotifen in a variety of forms including lozenges and drops, which are great for my pediatric population, and tablets and capsules, which are great for my adult population. 

When first started on Ketotifen, some patients may experience fatigue. Because of this, I tend to start patients on a very tiny dose and then increase the dose as tolerated. I find that it usually takes about a month for patients to work their way up to a dose that works for them without experiencing too much fatigue. However, many of my patients with chronic pain also have difficulty sleeping. So Ketotifen can be really helpful if insomnia is a part of your symptom picture.

Quercetin

Quercetin is a naturally-occurring polyphenol flavonoid that has antioxidant and anti-inflammatory effects. It is can be found in several fruits, vegetables, and teas:

  • Onions

  • Capers

  • Apples

  • Berries

  • Tomatoes

  • Grapes

  • Brassica vegetables such as broccoli

  • Black and green tea

Quercetin is considered safe and has even been shown to protect the cells of the liver and kidney.⁶ Quercetin is used to treat pain because of its ability to stabilize the membrane of the mast cell.⁷ Stabilization of the mast cell membrane decreases the amount of histamine and other pro-inflammatory compounds that are released. Because pain is a result of the compounds that are released by mast cells, a mast cell stabilizer can help treat pain. 

Depending on the patient, the dosage of Quercetin ranges from 500 mg to 3000 mg daily. When taking Quercetin, it is important to make sure you use a brand without fillers. This is how Quercetin is the most effective. There are several brands that I recommend. 

The Jarrow brand comes in 500 mg capsules, which makes it easier if you need a higher dose of Quercetin to stabilize your mast cells and treat your pain. 

There is also a company called bulksupplements.com which is one of the only stores to sell supplements in bulk without any fillers. 

Urtica dioica

Urtica dioica is a wild flowering plant that is commonly known as stinging nettle. Stinging nettle has long been used to treat conditions such as joint pain, rheumatism pains, and even allergies. Stinging nettle has been found to suppress the inflammatory compounds that are released by mast cells. By doing so, pain that is caused by mast cell activity can be treated. 

Furthermore, stinging nettle has been found to contain similar anti-inflammatory properties to pain medications like ibuprofen and aleve. Stinging nettle leaf has been shown to have anti-nociceptive effects. In other words, stinging nettle helps the body not feel as much pain as the nerves are expressing. In addition to treating pain and inflammation, stinging nettle can also help to:⁸

  • lower blood pressure 

  • fight off viruses

  • decrease toxins in the body

Urtica dioica can be a safe and effective way to manage chronic pain by decreasing inflammation in the body. 

The Importance of Mast Cell Stabilizers in Pain Management

When taken consistently, mast cell stabilizers have the potential to effectively treat pain in those who suffer from chronic pain.⁵ Since chronic pain is not something we can clinically test, often times a trial of one of these medications that decreases mast cell activation can be helpful to treat as well as to diagnose how much mast cell activity is contributing to chronic pain. 

Research continues to be conducted on mast cells, their communication with the autonomic nervous system, and their overall impact on human health. Because mast cells are located all over the body, mast cell activity can not only result in pain, but it can also contribute to other disease processes that are the result of chronic inflammation.