Itching, chloroquine, and malaria: a review of recent molecular and neuroscience advances and their contribution to mechanistic understanding and therapeutics of chronic non ‐histaminergic pruritus

AbstractChloroquine (CQ) is an antimalarial drug that elicits severe pruritus in black Africans with malaria fever. This acute itching (2 –7 days duration) exhibits age dependency and a racial and genetic predilection. CQ itch is non‐histaminergic, which makes it both a good model and a tool to probe the mechanisms of chronic itch. This review focuses on recently discovered mechanisms, neuroscience, mediators, and receptors that are implicated in molecular studies of CQ pruritus. CQ pruritus mechanisms are also compared to that of itching following other systemic diseases, such as chronic kidney disease, chronic liver disease, skin disorders, and burns. There are striking similarities between CQ itching pathways and other c hronic itch secondary to systemic disease with or without skin lesions, which have not been previously highlighted. Prominent among these are the shared roles of skin, neural and spinalμ opiate receptors, kappa opiate receptor, nitric oxide, serotonin via 5HT1B/D receptors, cytokines, especially interleukins, and tumor necrosis factor. There is elaborate “cross talk” among the diverse mediators and receptors involved in CQ‐induced pruritus. CQ also binds to the mas‐related G protein coupled receptors MrgprA3/MrgprX1 present in a small proportion (4–5%) of dorsal root ganglion neurons and skin. The mrgprA3 CQ receptors are coupled to PLC‐β3 and a chloride channel to initiate skin itch action potentials in C nerve fibers. Mrgpra3/X1 couple...
Source: International Journal of Dermatology - Category: Dermatology Authors: Tags: Review Source Type: research