Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus

Background: Histamine is a potent mediator of itch in humans, yet histamine H-1 receptor antagonists have been shown to be of limited use in the treatment of certain chronic pruritic diseases. The histamine H-4 receptor is a recently described histamine receptor, expressed on hematopoietic cells, linked to the pathology of allergy and asthma. Objective: The contribution of the novel histamine H-4 receptor to histaminergic and allergic pruritus was investigated. Results: Histamine and a selective histamine H-4 receptor agonist caused scratching responses in mice, which were almost completely attenuated in histamine H-4 receptor knockout mice or by pretreatment with the selective histamine H-4 receptor antagonist, JNJ 7777120. Pruritus induced by allergic mechanisms was also potently inhibited with histamine H-4 receptor antagonist treatment or in histamine H-4 receptor knockout mice. In all cases, the inhibitory effect of histamine H-4 receptor antagonist was greater than those observed with histamine H-1 receptor antagonists. The histamine H-4 receptor-mediated pruritus was shown to be independent of mast cells or other hematopoietic cells and may result from actions on peripheral neurons. Conclusion: These results demonstrate that the histamine H-4 receptor is involved in pruritic responses in mice to a greater extent than the histamine H-1 receptor. Clinical implications: Histamine H-4 receptor antagonists may have therapeutic utility for treating chronic pruritic diseases in humans where histamine H, receptor antagonists are not effective.