title: Caffeic acid exhibits anti-pruritic effects by inhibition of multiple itch transmission pathways in mice.
abstract: Itch is an unpleasant sensation that evokes a desire to scratch. Although often regarded as a trivial 'alarming' sensation, itch may be debilitating and exhausting, leading to reduction in quality of life. In the current study, the question of whether caffeic acid can be used to alleviate itch sensation induced by various pruritic agents, including histamine, chloroquine, SLIGRL-NH2, and β-alanine was investigated. It turned out that histamine-induced intracellular calcium increase was significantly blocked by caffeic acid in HEK293T cells that express H1R and TRPV1, molecules required for transmission of histamine-induced itch in sensory neurons. In addition, inhibition of histamine-induced intracellular calcium increase by caffeic acid was demonstrated in primary cultures of mouse dorsal root ganglion (DRG). When chloroquine, an anti-malaria agent known to induce histamine-independent itch - was used, it was also found that caffeic acid inhibits the induced response in both DRG and HEK293T cells that express MRGPRA3 and TRPA1, underlying molecular entities responsible for chloroquine-mediated itch. Likewise, intracellular calcium changes by SLIGRL-NH2 - an itch-inducing agent via PAR2 and MRGPRC11 - were decreased by caffeic acid as well. However, it was found that caffeic acid is not capable of inhibiting β-alanine-induced responses via its specific receptor MRGPRD. Finally, in vivo scratching behavior tests showed that caffeic acid indeed has anti-scratching effects against histamine, chloroquine, and SLIGRL-NH2 administration but not by β-alanine. Overall, the current study demonstrated that caffeic acid has anti-itch effects by inhibition of multiple itch mechanisms induced by histamine, chloroquine and SLIGRL-NH2.
authors.affiliation: College of Pharmacy, Gachon University, Hambakmoeiro 191, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Sabindra
authors.initials: S
authors.lastname: Pradhananga
authors.affiliation: College of Pharmacy, Gachon University, Hambakmoeiro 191, Yeonsu-gu, Incheon 406-799, Republic of Korea. Electronic address: wsshim@gachon.ac.kr.
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Shim
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology; D057809:HEK293 Cells; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008610:Menthol / Q000494:pharmacology; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D044464:Receptor, PAR-2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects*; D050053:TRPM Cation Channels / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D002738:Chloroquine; D006632:Histamine; D008610:Menthol; D009842:Oligopeptides; D044464:Receptor, PAR-2; D043562:Receptors, G-Protein-Coupled; D011969:Receptors, Histamine H1; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C470192:Mrgprx1 protein, mouse; C492297:TRPM8 protein, mouse; C493921:TRPV1 protein, mouse; C099570:seryl-leucyl-isoleucyl-glycyl-arginyl-leucine; C040048:caffeic acid
keywords: Caffeic acid; Calcium imaging; Dorsal root ganglia; Itch; Scratching; Sensory neuron