Mast Cell Disease & Fibromyalgia (FM): Can Mast Cell Degranulation Cause FM Symptoms?

Along with a multitude of other coexisting conditions, many mast cell disease (MCD) patients have been diagnosed with fibromyalgia (FM). Unfortunately, most fibromyalgia patients have never heard of mast cell disease and neither have their doctors.

Many of us with MCD get our FM diagnosis before we ever hear the words “mast cell” but once we understand the connection between these two diseases it’s easy to see how our dysfunctional mast cells can contribute to some of the pain and suffering brought on by FM.

First, what is fibromyalgia?

Fibromyalgia is a disorder that causes aches and pain all over the body. Patients have “tender points” throughout their bodies. These are specific places on the neck, shoulders, back, hips, arms, and legs that hurt when pressure is put on them.

What are the symptoms of fibromyalgia?

In addition to pain, people with fibromyalgia may also experience:

  • Cognitive and memory problems (sometimes called “fibro fog”)
  • Sleep issues
  • Morning stiffness
  • Headaches/Migraines
  • Irritable bowel syndrome
  • Painful menstrual periods
  • Numbness or tingling of hands and feet
  • Restless leg syndrome
  • Heat/cold sensitivity
  • Sensitivity to loud noises or bright lights

These are identical to many of the symptoms of mast cell disease. Is this just a coincidence? Perhaps not. There is a lot of research that shows a connection between mast cell degranulation and fibromyalgia.

In one study published on PubMed, the title says it all, really:

“Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells.”

In it, the researchers report:

We had previously shown that CRH and SP stimulate IL-6 and TNF release from mast cells (MCs). Our current results indicate that neuropeptides could stimulate MCs to secrete inflammatory cytokines that contribute importantly to the symptoms of FMS. Treatment directed at preventing the secretion or antagonizing these elevated neuroimmune markers, both centrally and peripherally, may prove to be useful in the management of FMS.

In another research study, also from PubMed, the experts question whether it is skin mast cells directly contributing to FM symptoms or instead the sensory nervous system’s response to certain harmful or potentially harmful stimuli triggering mast cells to degranulate.

They also tested ketotifen, a mast cell stabilizer, on patients with FM. The results? Not that promising. Oral ketotifen was not shown to improve pain levels at the doses given in the study:

The study results question whether skin mast cells play a major role in the pathogenesis of FM. However, given the role of mast cells in peripheral and central nociception, and the minimal side effects of ketotifen, a randomized clinical trial using increasing doses of ketotifen may be warranted.

Another group of researchers looked into skin MCs contributing to FM and had a similar finding:

Our results indicate that FMS is a MC-associated condition. MCs are present in skin and mucosal surfaces throughout the human body, and are easily stimulated by a number of physical, psychological, and chemical triggers to degranulate, releasing several proinflammatory products which are able to generate nervous peripheral stimuli causing CNS hypersensitivity, local, and systemic symptoms. Our findings open new avenues of research on FMS mechanisms and will benefit the diagnosis of patients and the development of therapeutics.

Tricyclic antidepressants (TCAs), like Doxepin, have proven helpful in treating both MCAD and Fibromyalgia, according to research published here:

Amitriptyline and doxepin are the most commonly studied TCAs in fibromyalgia. A meta-analysis of nine controlled studies of tricyclics showed significant improvement in pain, stiffness, tenderness, fatigue and sleep quality when compared with placebo.

In yet another study, the experts hypothesize that using mast cell disease approved therapies and other mast cell stabilizing agents, such as doxepin, luteolin and quercetin, may help with FM:

The hypothesis is put forward that FMS is a neuro-immunoendocrine disorder where increased release of CRH and SP from neurons in specific muscle sites triggers local mast cells to release proinflammatory and neurosensitizing molecules. There is no curative treatment although low doses of tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron, are helpful. Recent nutraceutical formulations containing the natural anti-inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they can be used together with other treatment modalities.

Of course, fibromyalgia is a complex and difficult to treat condition. It is still poorly misunderstood and more research needs to be done to determine the connection between mast cell activation and the true pathogenesis of this disease. Some treatments for MCAD may be more effective than others for treating fibromyalgia.

The experts all seem to agree on this, and the general consensus is:

Effective management of fibromyalgia symptoms is complex and requires a multidisciplinary approach evaluating pain, function and the psychosocial milieu of the fibromyalgia patient. Response and tolerance to treatment varies among patients. Nonpharmacological interventions are a necessity and complement drug therapy. A ‘strategic polypharmacy’ approach using drugs with different mechanisms of action can be helpful. An organized approach that manages the worst symptom first can facilitate easier management of the other symptoms. Effective symptom control is expanding as the underlying pathophysiology of fibromyalgia becomes clearer. The emergence of novel agents that are more effective in shutting down central sensitization may be more effective in treating this disabling condition. The provider can help by believing in the patient, and evaluating and treating the patient systematically.

One thought on “Mast Cell Disease & Fibromyalgia (FM): Can Mast Cell Degranulation Cause FM Symptoms?

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