So you've ergonomically optimised your workspace, but your wrist is still having some trouble working that mouse. If your wrist pain just won't seem to go away, try a vertical mouse that completely changes your stance.
Redditor bmaya was having a bit of wrist trouble, so he put together this DIY vertical mouse out of a wooden block, a few buttons, and a bit of electronics work. It isn't pretty, but it works, and if you know your way around a circuit board, it's a cheap way to see if a vertical mouse is right for you.
Of course, if you decide that you do like it, you can actually buy a vertical mouse like the ever-popular Evoluent Vertical Mouse or the slightly cheaper, joystick-like 3M Ergonomic Mouse. If minor adjustments aren't helping your RSI, it could be a good solution.
Built myself a vertical mouse [Reddit]