Mast cells are best known for their role in allergic reactions, but recent research shows they also contribute to itching and pain in many other conditions via neuroimmune interactions. Inhibiting their activity may offer new treatment strategies for these distressing symptoms.
Omnipresent in the body, mast cells are central regulators of the immune system. However, they can also turn against our well-being, and not just in the form of allergies and anaphylactic reactions. In an invited review published in Immunological Reviews, Professor Ilkka Harvima of the University of Eastern Finland and Professor Kalpna Gupta of the University of Minnesota explain how the interactions of mast cells with the neural system contribute to a variety of pathological conditions. These include itch symptoms common in psoriasis and atopic dermatitis. Mast cells also contribute to pain in conditions such as mastocytosis, sickle cell disease and cancer.
Mast cells can release substances and mediators like histamine, tryptase and substance P, known for their ability to produce itching and pain. The resulting feedback from neural nociceptors may cause a vicious circle of mast cell activation and peripheral nerve sensitisation, leading to neurogenic inflammation and itching or pain, and possibly even promoting a transition from acute to chronic symptoms. Similarly, mast cells can amplify neuroinflammation in the brain.
Thus, researchers have started to seek new treatments based on mast cell inhibition. For example, in atopic dermatitis, the combined antagonism of histamine receptors H1 and H4 on sensory nerves has shown promising signs in the relief of itching and inflammation. Other, non-histaminergic targets for anti-itch treatments could be the cytokine IL-31, the nerve growth factor NGF, and the PAR-2 receptor.
In the treatment of chronic pain, the use of opioids has been shown to activate mast cells, which may even worsen the symptoms. According to the review, this could possibly be avoided and opioid dosage could be reduced by administering mast cell stabilising agents together with opioids.