Nerves
Histamine has a profound impact on the nervous system and the experience of pain. It can sensitize nerve endings, amplifying pain signals and contributing to conditions like migraines, fibromyalgia, and chronic widespread pain.
When mast cells release histamine near nerves, it can lead to heightened sensitivity, burning sensations, or even neuropathic pain. This neuroinflammatory response is also linked to dysregulation of the autonomic nervous system—manifesting as symptoms like dizziness, heart palpitations, and temperature intolerance. For many with unexplained or persistent pain, histamine-driven nervous system activation may be a hidden driver.
Fibromyalgia
Pain is a massive sign of MCAS. Mast cells live near nerves. They are in constant communication with nerves. Imagine mast cells leaking inflammatory chemicals right in the neighbourhood of a family of nerves. This is pain.
Other pain conditions associated with mast cells are migraines, endometriosis, painful bladder syndrome and vulvodynia.
Other clues to the connection between fibromyalgia and histamine is in the treatment. DAO can significantly reduce pain when supplemented in pain syndromes. In fact, women with fibromyalgia tend to have lower DAO levels.
POTS/Dysautonomia
What is the relationship between POTS and MCAS?
POTS is a medically poorly understood condition. Layer that onto MCAS, another murky medical puzzle, things become easily misdiagnosed and overlooked.
MCAS is a condition that often affects our nervous system. The overlap between POTS and MCAS is estimated to be around 30%. The more dysfunction there is in our nervous system as in POTS, the more overactivation of the immune system there is, as in MCAS.
Honouring the interactions between these two conditions is key to developing a comprehensive plan to manage them.
Let’s clear up the muddy waters in our online course. Dive on in.
Ehler’s Danlos Syndrome (EDS)
Connective tissue disorders have strong overlap with MCAS and respond well to MCAS treatments.
24% of MCAS patients also have EDS.
Up to 95% of patients with EDS benefit from anti-histamine therapy.
EDS and MCAS coexist, creating a complex clinical picture marked by widespread, multisystem symptoms. In EDS, dysfunctional connective tissue may predispose mast cells—located throughout connective structures—to inappropriate activation, leading to excessive release of histamine and other inflammatory mediators. This can contribute to symptoms like flushing, GI distress, fatigue, and neurological issues, which often overlap with the effects of autonomic dysfunction, particularly in patients who also have POTS (Postural Orthostatic Tachycardia Syndrome). Together, this triad—EDS, MCAS, and POTS—represents a challenging yet increasingly recognized constellation that demands an integrative, patient-specific approach to diagnosis and treatment.
