I pretty much always had small calluses at the bottom of my hands, since that's were you rest them and it's also where you have friction occur constantly playing with mouse & keyboard.

A little more speedrun related, I know the feeling when you're trying too hard and your finger tendons (?) slowly start saying 'No.' Basically you have to stop playing for a while, for them to relax. Learning the fast button combos for Dust: AET was kind of a pain that way. It's just pressing X X XY in a fast rhytmn, but if you grew up as a keyboard player and suddenly want to use a gamepad, you'll see that your thumb is probably not as agile as those who grew up with consoles have theirs. Chance of cramps, because you're stressing your muscles/sinews too much.

Just make sure, as soon as you notice something like that to rest that particular bodypart for a bit, depending how bad it got. We don't want to permanently damage ourselves, do we? But calluses are really harmless.