These are my notes from the article "Mast cell activation syndrome and the vagus nerve"
written by Ross Hauser, MD of Caring Medical on February 4, 2023
Many patients diagnosed with MCAS (Mast Cell Activation Syndrome) also have neck pain that is diagnosed as (or can be described as) upper cervical instability or cervical spine instability. It is generally assumed that this pain is part of the existing illness, but in this article Dr Hauser explains that the causality could be going the other way. Many of these patients are also diagnosed with Chronic Fatigue Syndrome, Myalgic Encephalomyelitis (ME/CFS), POTS, or some other form of Dysautonomia. When these patients see specialists to see if the neck pain and problems could be causing some of their symptoms, some are then diagnosed with "degenerative disc disease in their cervical spine and a loss of the cervical curve contributing to kyphosis".Dr Hauser explains that:
"Which brings us to an important question, which came first? Autonomic nervous dysfunction or immune-mediated allergy? At a minimum, we know they are interconnected. A lot of antigen-antibody immune complexes and a host of histamine releases are going to excite the autonomic nervous system throughout and likewise, autonomic nervous system dysfunction makes antigen-antibody reactions more likely. The patient has the symptoms, is it the neck causing them? Is it the allergies?"
He explains that the way cervical instability could lead to symptoms of MCAS, etc, is because it may be causing the vagus nerve to be pinched or compressed in the neck or: "damaged cervical ligaments’ inability to hold the “wandering” vertebrae in place." The vagus nerve is how signals from the brain reach the viscera (the organs in your torso) in order to control them, so anything that impedes its function can have major consequences:
"When the vagal nerve sensory afferents are dysfunctional, the important body sensors for homeostasis are switched off. Cervicovagopthy or vagus nerve disorder brought on by cervical spine instability, has wide-ranging negative effects on mucosal barriers in the intestines and lungs, producing a large number of inflammatory mediators, including histamine."
Dr Hauser explains that many patients who fit this profile- having MCAS along with many of the following additional diagnoses- EDS (Ehlers-Danlos Syndrome, POTS (Postural Orthostatic Tachycardia Syndrome), Gastroparesis, Fibromyalgia, sleep disturbances, low blood pressure, serious gastrointestinal pain and dysfunction, "When someone has a myriad of symptoms like this, it is of course difficult to believe they all start spontaneously without a common thread linking them together. In a person like this, when all is a mystery, we follow the neurology, we look for short-circuiting messages between brain and body being caused by compression of the arteries, veins, and the nerves that travel through the cervical spine."
Dr Hauser notes that many of the different disorders and symptoms experienced by these patients Do have established connections and that these connections are further evidence of vagus nerve involvement. A key example of this is the interconnection between the immune system and the gut, mediated by the vagus nerve, in which modulating signals are sent both ways. Also, regulating signals and neurotransmitters in this system are part of the mechanism that the body uses to turn inflammation on and off. To explain this he quotes a may 2021 study in the journal Frontiers in Pharmacology:
“Inflammatory bowel disease, irritable bowel syndrome, and severe central nervous system injury (of which the vagus nerve plays a dominant role) can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation (movement, or better thought of as escaping to other parts of the body) to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases.”
"The researchers add that repairing the intestinal barrier represents a potential therapeutic target for many diseases. Repair means addressing the dysfunction of enteral afferent nerves, efferent nerves, and the intrinsic enteric nervous system that play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors."
"Histamine is synthesized by mast cells, basophils, platelets, histaminergic neurons, and enterochromaffin cells, where it is stored intracellularly and released upon stimulation. It can be found basically everywhere in the body, including the spinal cord and brain. Histamine causes smooth muscle cell contraction, vasodilation, increased vascular permeability and mucus secretion, tachycardia, alterations of blood pressure, and arrhythmias, while it stimulates gastric secretion and nociceptive nerve fibers. Histamine increases secretions such as hydrochloric acid in the stomach and is vital to protecting the lungs and gastrointestinal tract from infections. When histamine levels are high, increased secretions in the lungs, therefore, cause coughing, phlegm production, sneezing, and diarrhea occur in the digestive tract in an attempt by the body to rid itself of an infectious agent or toxin."
When the transmission of nerve impulses along the vagus nerve from the brain are interrupted or stopped, this can limit the body's ability to regulate and maintain homeostasis (balance of systems), which can keep the body from appropriately limiting the inflammatory response. It also results in higher histamine content of mast cells, mast cells being more responsive to nerve signals to react, which ultimately means a higher level of histamine in the organs systems.
"The GI tract harbors the largest population of mast cells in the body and is thus the main reservoir of the body’s histamine. The mast cells’ job is to maintain intestinal permeability and make sure that no microorganisms or antigens enter the body. (A dysfunction of this system can lead to Leaky Gut Syndrome and inflammation of the intestines.) The neurological control over mast cells and their various digestive functions is via the vagal influences on the enteric nervous system. Elevated histamine levels in the body occur when there is an increase in intestinal permeability (regardless of the cause), including that from synthetic foods (industrial food additives, chemicals in food, genetically modified foods), Ehlers-Danlos syndrome (EDS), and cervical spine instability induced cervicovagopathy."
The effects of histamine on gut function, and how this impacts other disease processes especially autoimmune, has been well-studied. Some common industrial food additives are known to trigger mast cells to make the gut more permeable (increase the amount of space between cells that line the gut and regulate what gets into the bloodstream and what doesn't), allowing larger proteins than usual into the bloodstream. Once there, these proteins can trigger allergic and other inflammatory responses and are especially associated with autoimmune disease.
"Histamine intolerance results from excessive histamine and a decreased ability to absorb or neutralize it. Elevated levels of histamine give symptoms that mimic allergic reactions, and these include diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritis, flushing, and skin lesions. A true allergy is tied to IgE-mediated histamine release, which is to be differentiated from histamine intolerance. The latter is associated with some forms of urticaria, eczema, asthma, food sensitivity, migraines, and chronic GI and neurological ailments, including inflammatory and irritable bowel syndromes."
"The reservoir of histamine in the body originates in the gut and comes from the breakdown of food that is ingested or the microbiota-generated histamine. Histamine intolerance is akin to lactose intolerance in that the body is missing a key enzyme to digest a food substance. In histamine intolerance, it is DAO in the digestive tract, a deficiency of which leads to elevated histamine levels in the body. DAO is synthesized by the intestinal villi (enterocytes) and is constantly released from the intestinal mucosa into the gut, as well as the blood circulation, during eating and digestion."
Mast cell dysfunction is also being increasingly recognized as a major part of many neurological and psychiatric disorders, especially neurodegenerative disease. "What is being suggested is that the Mast cells are causing runaway neurological inflammation by excerpting a disruptive influence (bad messages) on the central nervous system and brain and this is leading to neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease for example."
"vagal activity, partially driven by gastric mast cells, induces long-lasting changes in corticotrophin-releasing factor signaling in the amygdala that may be responsible for enhanced pain and enhanced anxiety- and depression-like behaviors."
"What they found was vagus nerve stimulation resulted in a significant reduction of the different inflammatory parameters assessed. They said their results underscore the anti-inflammatory properties of the vagus nerve and the potential of neuro-immune interactions in the intestine. In other words, if the vagus nerve is working correctly, anti-inflammatory and mast cell activation could be suppressed."
Further Information from Dr Hauser:
Can Chronic fatigue syndrome and Myalgic encephalomyelitis be caused by cervical stenosis and cervical spine instability?
Postural Orthostatic Tachycardia Syndrome (POTS), the Vagus Nerve and Cervical Spine instability
Cervical Curve Correction – Caring Cervical Realignment Therapy
Research Articles Cited in this Article (not all):
How to evaluate the patient with a suspected mast cell disorder and how/when to manage symptoms
Diagnosis of mast cell activation syndrome: a global "consensus-2"
Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay
The Gut's Little Brain in Control of Intestinal Immunity
Vagal gut-brain signaling mediates amygdaloid plasticity, affect, and pain in a functional dyspepsia model
