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Chronic Pain and the Histamine / Mast Cell Connection

Updated: Feb 27

Pain is a debilitating symptom. It can have a profound impact on quality of sleep and be correlated to depression (1).

Pain can originate from the nervous system. This is different than pain that comes from injury to tissues such as muscle or bone.

When pain comes from the nervous system it is called neuropathic pain or neuropathy.

What role does histamine play here?

Histamine and histamine receptors play an integral role in neuropathic pain. Histamine is one of the neurotransmitters involved in the normal pain response. It is normally released when tissue injury occurs. With high histamine levels due to Histamine Intolerance or Mast Cell Activation Syndrome, a pain response can be triggered without injury.

Histamine binds to 4 different types of receptors on cells. H3 receptors are one type of histamine receptor that is found predominately in neurons (nerve cells). (Remember neurons, from yesterday's blog? Check it out here.)

Studies using rat models demonstrate that blocking the H3 receptor with an antagonist reduces neuropathic pain (2). Antagonist in this sense means a drug that counteracts the effects of the histamine on that receptor.

These studies demonstrate the significant role of histamine in neuropathy. Human studies have yet to be conducted, and these antagonists are currently not commercially available.

H1 and H2 blockers may provide some relief (3). Discuss these with your doctor. If you have Mast Cell Activation Syndrome, you may want to discuss compounded versions of these with your doctor to avoid the risk of reacting to fillers in the over-the-counter versions.

Linking histamine and mast cell activation with chronic pain symptoms

Histamine and mast cell activation have been correlated to numerous conditions that have pain as part of the symptom profile. These include:

  • Burning Mouth Syndrome (4)

  • Complex regional pain syndrome (5)

  • Chronic Fatigue (6)

  • Crohn’s/colitis (7, 8)

  • Endometriosis (9)

  • Fibromyalgia (10, 11)

  • IBS (12)

  • Hypermobile Ehlers-Danlos Syndrome (EDS) (13)

  • Interstitial Cystitis (14)

  • Rheumatoid Arthritis (15)

  • Systemic Lupus (16)

Have you been diagnosed with any of these conditions? Could your pain possibly be histamine mediated?

First up, check out our Histamine Symptom List to see if any of your other symptoms could be histamine mediated too. Is it time to consider a dietary approach to manage histamine levels, in order to alleviate some of the contributing factors to your chronic pain?


Want to learn more about histamine issues, and how it can play in to your symptoms you experience on a daily basis?

Join us at our next live Master Class, The Histamine Connection. We talk about the role histamine and mast cells can play in the driving of your symptoms, including pain. Need help in making that connection? Register for the next one by heading to this page.

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