Elsevier Inc. Bdkrb2 Bdkrb1 KD ---> vasodilation KD ---> inflammatory mediators release kinin signaling pathway Kng1 des-Arg-kinins ---> vasodilation inflammatory mediators release des-Arg-kinins ---> sensory neuron stimulation vasodilation sensory neuron stimulation KD BK lowKng1 highKng1 Serping1 Serping1 ---| Klkb1 Serping1 ---| F12a KD ---> des-Arg-kinins Bdkrb2 ---- KD Bdkrb1 ---- des-Arg-kinins des-Arg-kinins ---> inactive kinins pKlkb1 highKng1 ---- pKlkb1 F12 --+> F12a F12 Kng1 ---> highKng1 F12a BK ---> inactive kinins KD ---> inactive kinins Kng1 ---> lowKng1 coagulation cascade pathway classical complement pathway Serpina4 Prcp Klkb1 Klk1 Cpn1 Cpm A2m Klkb1 --+> F12a F12a --+> coagulation cascade pathway F12a --+> classical complement pathway A2m ---| Klkb1 F12a --+> Klkb1 Prcp --+> Klkb1 lowKng1 ---> KD highKng1 ---> BK Serpina4 ---| Klk1 BK ---> des-Arg-kinins BK ---> vasodilation BK ---> inflammatory mediators release KD ---> sensory neuron stimulation BK ---> sensory neuron stimulation des-Arg-kinins ---> inflammatory mediators release inactive kinins kininases des-Arg-kinins Bdkrb2 ---- BK