MPC HC is shorthand for Media Player Classic Home Cinema. A popular, open source media player. It has keyboard shortcuts, but they are not global shortcuts. MPC HC needs focus for them to work. They do not interfere with any other program except Paint.NET
It seems there is a bug with Paint.NET because another program should not be able to cause issues like this. The Ctrl, Shift and R keys all work OK and can be tested, so Paint.NET should activate the shortcut when pressed.