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This acute itching (2\u20137\u00a0days duration) exhibits age dependency and a racial and genetic predilection. <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content> itch is non\u2010histaminergic, 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 <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content> 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 <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content> itching pathways and other chronic 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 spinal <jats:italic>\u03bc<\/jats:italic> opiate receptors, kappa opiate receptor, nitric oxide, serotonin via 5<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>1B\/D receptors, cytokines, especially interleukins, and tumor necrosis factor. There is elaborate \u201ccross talk\u201d among the diverse mediators and receptors involved in <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>\u2010induced pruritus. <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content> also binds to the mas\u2010related G protein coupled receptors MrgprA3\/MrgprX1 present in a small proportion (4\u20135%) of dorsal root ganglion neurons and skin. The mrgprA3 <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content> receptors are coupled to <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u2010<jats:italic>\u03b2<\/jats:italic>3 and a chloride channel to initiate skin itch action potentials in C nerve fibers. Mrgpra3\/X1 couples to <jats:styled-content style=\"fixed-case\">TRPA<\/jats:styled-content>1 for calcium influx into neuronal cells at noncutaneous sites. Central <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content> itch occurs via gastrin\u2010related peptide (<jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>) and its receptor (<jats:styled-content style=\"fixed-case\">GRPR<\/jats:styled-content>) in the dorsal spinothalamic tracts, as well as glutamic mediated <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content> projection to parabrachial nucleus. The possibility of chronic itch therapy based on personalized medicine, genetics, and transcriptomics or the use of itch \u201cpolypill\/polycream\u201d are discussed.<\/jats:p>","DOI":"10.1111\/ijd.14252","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T09:39:38Z","timestamp":1540546778000},"page":"880-891","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Itching, chloroquine, and malaria: a review of recent molecular and neuroscience advances and their contribution to mechanistic understanding and therapeutics of chronic non\u2010histaminergic pruritus"],"prefix":"10.1111","volume":"58","author":[{"given":"Adesuyi A. 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