Mast Cells and Histamine Receptors Cause Pain in Interstital Cystitis (IC) and We Must Deal Better With Peripheral Pain Generators

Startling findings from gene deletion mice experiments implicate mast cells and histamine receptors in IC. It is also implicated that other peripheral sensitizations might follow that process.

PLoS ONE. 2008 May 7;3(5):e2096.
Mast cell-derived histamine mediates cystitis pain.
Rudick CN, Bryce PJ, Guichelaar LA, Berry RE, Klumpp DJ.
abstract here

1) Bladder insult via pseudorabies virus infection induces “neurogenic cystitis” – neurologically based continued inflammation. Interestingly, this can be done by chemical based damage to the bowel, which hypersensitizes nerves both bladder and bowel nerves.

2) “both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow.”

3) Tumor Necrosis Factor (TNF) is an inflammatory chemical released by the neurogenic inflammation; it induces damage to the bladder barrier. In TNF receptor deficient mice, these pathological changes did not occur, but the pain still occurred.

4) “genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology”.

Comment –

  • mast cells are becoming more and more implicated as the cause of peripheral neurogenic inflammation.
  • It is my belief that much of the central sensitization is peripherally driven and that religious devotion to central sensitization approaches through exercise and mindfulness approaches will not give sufficent relief without attention to these peripheral generators.
  • Case in point:

Pain. 2007 Sep;131(1-2):219-25. Epub 2007 May 16.A role for peripheral afferents in the pathophysiology and treatment of at-level neuropathic pain in spinal cord injury? A case report.

Wasner G, Naleschinski D, Baron R. Prince of Wales Medical Research Institute, Gate 1 Barker St., Randwick, Sydney, NSW 2031, Australia. g.wasner@unsw.edu.au

At-level neuropathic pain is a frequent symptom following spinal cord injury, but the underlying pathophysiology is not completely understood. We report a patient suffering from treatment-resistant at-level pain characterized by ongoing pain and mechanical allodynia for three years after an incomplete spinal lesion. Quantitative sensory testing revealed severe thermosensory deficits in the neuropathic pain area. However, topical application of capsaicin in the neuropathic pain area induced a burning pain sensation, a marked decrease in heat pain threshold and an increase in mechanical allodynia. Treatment with topical lidocaine patches (5%) led to considerable pain relief. These results indicate a functional connection between peripheral, spinal and supraspinal nociceptive pathways and that peripheral afferents may contribute to at-level neuropathic pain after spinal cord injury in this patient. Lesioned peripheral afferents in combination with central neuronal hyperexcitability are discussed as a likely underlying pain mechanism.

  • I suspect other peripherally directed measures would have worked too. But my feeling was again “My god, didn’t anybody bother to turn out the lights???” [ie the peripheral pain generators]. Opioids and central acting agents are fine but I still feel that people actually have to get their hands dirty and deal with peripheral pain generators – a phenomenon done less and less by opioid based medical approaches and exercise based physiotherapy approaches. It took the above case THREE years of constant pain to get that undertaken.
  • I have new respect for histamine as a source of pain. In IC, I use hydroxyzine, a H1 anti-histamine found to help, but have neglected to add a H2 blocker like ranitidiine (Zantac). I now use both. SO Hydroxyzine 10-50 mg QID and Ranitidine 150 bid (although I have heard of using 300 mg BID).
  • There are Histamine receptors in the brain, and dysfunction of them in the cingulate (the pain suffer centre) is associated with depression. abstract here When people with multiple chemical sensitivity smell something, the smell center is not so much activated as areas like the cingulate which I wonder is part of their suffering.
  • Mast cells do double duty – they are also allergy cells. In irritable bowel, mast cells congregate around bowel nerves that I presume have signaled them in for a peripheral sensitization frenzy and are three times higher than “normal” bowels. Although system allergy is rare, one wonders if these sensitized mast cells might be trigger happy to certain foods beyond actual allergy. Years ago, it was found prostaglandin output in the bowel secretions was considerably higher in irritable bowel. I suspect these increased and sensitized mast cells have found something to do…
  • Foods are a problem in IC and what factors contribute is important as well.

One wonders how much mast cells contribute to other peripheral sensizations (in TMJ, facets, and so one.). Also – what cross reactivity to food are present – am interested in views and what has been found helpful…

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One Response to Mast Cells and Histamine Receptors Cause Pain in Interstital Cystitis (IC) and We Must Deal Better With Peripheral Pain Generators

  1. Tania Nordli says:

    I am a physician working in a centre where patients are referred by primary care physicians.
    I find in a number of people, that a significant proportion of patients’ pain relates to histamine and tyramine intake in the diet. Tools useful in evaluating this are an allergy and sensitivity evaluation form and a week long diet and symptom history.

    I find the work of Janice Joneja PhD, RD originally developed for treating people with allergy, most useful.

    Also, I find a number of people with chronic pain seem to have an autoimmune response triggered by antigens in food, the focus may be at sites of previous trauma, or a more generalized response. I wonder if it is a similar phenomenon to that of the koebner phenomenon in psoriasis.

    The only tools I find useful at this point in evaluating who might benefit from diet interventions are: allergy and sensitivity evaluation forms, diet and symptom records, lab ;antitransglutaminase, IgA, ANA, CRP, ESR, vitamin D levels, ferritin;
    and then as appropriate diet trials such as few foods elimination diet and sequential incremental dose challenge, irritable bowel diet, histmaine reduced diet, as directed by history, physical, lab and patient willingness.

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