NEUROPATHY EDUCATION
Updated: Oct 14
Nerve pain, burning, numbness and tingling are some of the most common struggles I hear about from people with Lyme and co-infections. For me personally, I had random shock pains and some neuropathy symptoms during heavy treatment, but then I was fine for years. My hardest struggle with it came when menopause and MCAS decided to become friends, and then brought severe neuropathy into their friend group. It has been awful. Here is what may be behind it, and what the research shows.
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IN THIS POST
-What neuropathy can feel like
-Two types you may hear about
-What can cause it
-My personal experience
-Mast cells and neuropathy
-Hormones and mast cells
-Stress and mast cells
-What your doctor may check
-What research has shown
WHAT NEUROPATHY CAN FEEL LIKE
-Numbness
-Tingling or prickling
-Burning
-Sharp, stabbing or electric feelings
-Aching pain
-Feet that feel colder than the rest of your body
TWO TYPES YOU MAY HEAR ABOUT
-Peripheral neuropathy: an injury to the nerves outside the brain and spinal cord. Dr. Marty Ross notes it is common in chronic Lyme.
-Small fiber neuropathy: affects the tiny nerves that carry pain and temperature signals from the skin. These small nerves also help run things you never think about, like your heartbeat, breathing, digestion and bladder.
-Standard nerve tests can miss small fiber neuropathy. A skin biopsy is one way doctors can find it.
WHAT CAN CAUSE IT
-Infections: Lyme, Bartonella and Babesia can all injure nerves. Lyme and Bartonella are thought to be more likely causes than Babesia.
-Overactive mast cells (MCAS), covered below.
-Inflammation: extra inflammation chemicals (cytokines) can inflame the nerves.
-Blood sugar problems, even when an A1c looks normal.
-Low vitamin B12, too much vitamin B6, or thyroid problems.
-Mold toxins, which can harm nerves and the energy centers (mitochondria) inside nerve cells.
-Heavy metals like lead and mercury.
-Some medications, including fluconazole, itraconazole, metronidazole, tinidazole, hydroxychloroquine (Plaquenil) and disulfiram.
MY PERSONAL EXPERIENCE
This one is personal for me. In May, after starting hormone replacement therapy, I noticed my toes turning red. Over the next month it got worse, with tingling, massive burning, and a hard time walking. At first I worried it was Bartonella. Sometimes it would turn one hand and one foot red. It became horrible and mentally draining, and I could not find help locally. I have had four horrible months of foot torture that took over my life, physically and mentally.
My doctor connected it to my mast cells and my hormones. When Pepcid was added, it shockingly reduced the neuropathy in my feet and hands.
I have also seen stress set off my flares many times. When stress hits me suddenly, my face turns red and flushed right away, and then the tingling and burning start. I kept wondering what I ate or what I took, but it was an internal trigger. I am sharing this because it is an uncommon connection, and it may be part of your story too.
MAST CELLS AND NEUROPATHY
Mast cells are immune cells that release histamine and many other chemicals. When they become overactive, called mast cell activation syndrome (MCAS), they can affect many parts of the body, including the nerves.
-A 2022 study led by Dr. Peter Novak, with Dr. Matthew Hamilton, tested people with mast cell disorders who had nerve symptoms. Skin biopsies showed small fiber neuropathy in 81% of those with MCAS, and in 80% of those with an inherited mast cell condition called hereditary alpha tryptasemia. All of them also had mild to moderate dysautonomia, and as a group, they had less blood flow to the brain when standing.
-Dr. Leonard Weinstock and colleagues (2023) list sensory neuropathies among the nerve symptoms of MCAS. They suggest mast cell chemicals may affect the nervous system, including the small nerve fibers.
-MCAS, POTS and hypermobile Ehlers-Danlos syndrome often show up together, and doctors think small fiber neuropathy may share some of the same causes.
-Mast cell triggers named by Dr. Weinstock include infections, mold toxins, SIBO, heavy metals, stress, certain foods and estrogen.
HORMONES AND MAST CELLS
-Dr. Tania Dempsey explains that mast cells have receptors for estrogen, progesterone and testosterone, so they can respond when your hormones shift. Estrogen tends to switch mast cells on, while progesterone may help calm them. Much of this research so far comes from animal studies.
-Dr. Jill Carnahan explains that estrogen can trigger histamine release from mast cells and lowers DAO, the enzyme that clears histamine. In midlife, progesterone often drops before estrogen does, which may let mast cell symptoms flare.
-Symptoms can change with the monthly cycle, in perimenopause and in menopause.
-Putting it together: hormone shifts can stir up mast cells, and overactive mast cells have been linked to small fiber neuropathy. Research has not proven that hormones cause neuropathy directly. If your symptoms change with your cycle or your hormones, ask your doctor whether mast cells could be part of your picture.
STRESS AND MAST CELLS
-Stress is a known mast cell trigger. Dr. Weinstock lists it among the triggers that can set off mast cells.
-Dr. Jill Carnahan explains that mast cells, the vagus nerve and the brain's emotion center communicate with each other. Ongoing stress and a body stuck in "fight or flight" can make mast cells more reactive.
-Mast Cell Action's 2026 pain guide, written by pain specialist Dr. Johanna Theron, explains that stress releases chemicals from mast cells and can make MCAS symptoms worse. It also explains that MCAS pain can feel burning, and that one mast cell chemical, tryptase, adds to nerve-type pain.
-A red, flushed face is one of the common signs of mast cells releasing their chemicals. Dr. Weinstock lists flushing among MCAS symptoms.
-Research has not yet shown that stress causes neuropathy flares directly, but stress stirs up mast cells, and overactive mast cells have been linked to small fiber neuropathy.
WHAT YOUR DOCTOR MAY CHECK
Neuropathy specialists often start with blood work to look for causes that can be treated. Ask your doctor which of these make sense for you.
Blood sugar
-Fasting glucose and A1c
-A 2-hour glucose tolerance test. Dr. Amro Stino of Michigan Medicine notes that a normal A1c alone does not rule out blood sugar related neuropathy.
-Fasting insulin, triglycerides and HDL cholesterol
Vitamins and minerals
-Vitamin B12, plus methylmalonic acid (MMA), which can show a B12 problem even when B12 looks normal
-Vitamin B6
-Thiamine (vitamin B1)
-Folate
-Vitamin D
-Ferritin and iron saturation
Immune and autoimmune
-ANA and ENA, which screen for autoimmune conditions
-Celiac disease (tTG-IgA)
-Protein electrophoresis and immunofixation, which look for abnormal proteins in the blood
General health
-Complete blood count (CBC)
-Kidney and liver function
-Thyroid (TSH, and ask about Free T3 and Free T4)
-Hepatitis C and HIV
Toxins and infections
-Heavy metals (urine test)
-Lyme and co-infection testing, including Bartonella and Babesia
Mast cells (if MCAS may be involved)
Dr. Weinstock's paper lists these tests used to help diagnose MCAS:
-Blood: tryptase, histamine, prostaglandin D2, chromogranin A and heparin
-Urine: N-methylhistamine, leukotriene E4 and 2,3-dinor prostaglandin F2 alpha
-Tryptase is most helpful when checked during a flare and compared with your normal level, and these tests can come back normal when you are not flaring.
Hormones (if they may be involved)
-If your symptoms started or changed with hormone therapy, your cycle, perimenopause or menopause, ask your doctor about checking estrogen (estradiol), progesterone and testosterone.
WHAT RESEARCH HAS SHOWN
-2024, Tulane University: in a lab study, live Lyme bacteria and even dead bacterial pieces caused inflammation and nerve cell death in nerve tissue taken from monkeys. Blocking certain receptors calmed this down. This was done in the lab and has not been tested in people yet.
-2019, journal PLOS ONE: 10 people with lingering Lyme symptoms after treatment all had small fiber neuropathy on skin biopsy, and all showed changes in blood flow to the brain. Their standard large nerve tests were normal. All 10 had aching pain.
Other common symptoms included numbness or prickling, lightheadedness, dry mouth or eyes, and cold feet. It was a small study, and the researchers said larger studies are needed.
RELATED POSTS
SOURCES
Lefaucheur et al., Lab Tests for Small Fiber Neuropathy, Frontiers in Neurology (2026)
Mast Cell Action, Dr. Johanna Theron, MCAS and Pain (2026)
Tulane University, Frontiers in Immunology (2024)
Weinstock et al., Journal of Personalized Medicine (2023)
Dr. Amro Stino, Michigan Medicine, Foundation for Peripheral Neuropathy (2022)
Novak et al., Annals of Allergy, Asthma and Immunology (2022)
LymeDisease.org, Lonnie Marcum, Nerve Damage in Chronic Lyme (2019)
Novak et al., PLOS ONE (2019)
Dr. Jill Carnahan, Hormones and Histamine (2026)
Dr. Marty Ross, Neuropathy guide (updated 2026)
Dr. Tania Dempsey, Hormones and Mast Cells (2024)
Disclaimer: Rise Above Lyme makes no claims about any possible benefit of using any product mentioned within this site. Always consult with your doctor before adding anything. The information shared is based on personal experience, years of accumulated researched resources from Lyme Literate doctors and polls conducted within Lyme groups from actual patient experience using these solution ideas.
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