The reaction "typically" comes from the "annointing" that is splat over their backs. When my hands start to bother me, I know it's bath time. However, I have also noticed that people that are not used to handling hedgehog, will tend to have a slight reaction whether the hedgie had a bath or not. Thus, I'm not sure if there is proof that you eventually build up an immunity to them with constant handling...or not. When I first started with hedgies, my hands did itch or sting quite a bit. But now, I rarely have any problems with it. Hope that helps!