My thumb, index finger and middle finger lock up and cause serious pain. why?

Couple things: You may have carpal tunnel syndrome (cts). The median nerve which is affected in cts innervates your thumb, index and part of our middle fingers. It could be that, especially if you notice it more often when your wrist is flexed. A couple of other things it could be: arthritis (especially if you use those three fingers most at work), combo of dequervaines and trigger fingers, or trauma.

?Trigger fingers: If they are truly locking, the it is probably a form of tendonitis knows as trigger finger. You should see a doctor, possibly a hand or orthopedic surgeon for treatment. Usually they respond to injection. If it is really a spasm, there are a number of possible reasons, including carpal tunnel syndrome, that should be checked out.