pd-168368 and Dermatitis--Allergic-Contact

Neuromedin B is expressed in nociceptive and itch-sensitive dorsal root ganglia neurons, but its peripheral pruritogenic potential is not well described. The potential of neuromedin B as a pruritogen and pro-inflammatory peptide in the skin was tested in vivo in an acute model in mice and monkeys as well as an allergic dermatitis model in mice. To identify the underlying mechanisms in vitro real time PCR analysis for neuromedin B and its receptor expression in murine mast cells and dorsal root ganglia as well as functional calcium imaging in the ganglia was applied. Neuromedin B induces itch when injected intradermally, and the peripheral signal is likely transmitted through the activation of dorsal root ganglia. Thus, neuromedin B could be an interesting new therapeutic target for peripheral processing of itch at the level of sensory neurons.

Topics: Animals; Calcium; Cell Degranulation; Cells, Cultured; Dermatitis, Allergic Contact; Female; Ganglia, Spinal; Gene Expression; Indoles; Injections, Intradermal; Macaca mulatta; Male; Mast Cells; Mice; Neurokinin B; Pruritus; Pyridines; Receptors, Bombesin; RNA, Messenger; Sensory Receptor Cells; Single-Cell Analysis; Toluene 2,4-Diisocyanate