When using Multiplicity, I span 5 screens using seamless mode.
Is that the 5th screen attached to a single PC?
I can use the mouse and manipulate icons, tasks, etc. The far right PC wont receive keyboard functionality, but the mouse still works.
This is to say that you can see the mouse move, but it can't interact with anything, yes?
The ability to bring the mouse back to the main PC is gone. I can not return to my main pc.
You can set up a hotkey to get it to the main PC

This is what I would recommend if your issue was immediate, not just after 'a few hours'
https://support.stardock.com/space/SHC/1288044590/I+can+move+my+mouse+to+the+Secondary+but+cant+interact+with+the+desktop
That said, something is likely happening with your firewall to prevent MP from working properly. Were I you, I would try to correlate it happening with something I have done, a 'it happens just after I do, run, change this'.
Sean Drohan
Stardock Product Lifecycle Manager