Firstly: RSI is no joke - if you're experiencing pain, there's a non-zero chance it'll develop into a serious medical condition. (At MIT's Media Lab, someone's RSI got so bad he couldn't type at all and had to invent an interface using vocal phonemes to encode common OS actions/lexical keywords to control his OS (OS X) / editor (emacs) / language of choice (python)).
If you feel even the slightest bit of pain, that's your body signalling to you 'hey buddy, don't do this'. I was suffering from emacs pinky to the point where my hands were aching hours after leaving my desk. On weekends, my tennis racket grip was significantly weaker and form poorer. Mapping Ctrl to caps, right shift to Esc, and buying a $30 MS Ergonomic keyboard solved my issues. My friends who have had worse issues spent the $300 on a Kinesis (which I had up until then considered to be snake oil) but it seems to have solved their issues entirely (and for $300 it's definitely a cheap investment compared to the opportunity cost of the time invested in physical therapy).
If you're on Linux, you can at the os-level make modal changes. I made the right-alt key move into a different mode, so I effectively get an entirely separate key-mapping when that key is depressed. (E.g., hjkl for me is OS-wide, and sdfg lets me move the cursor. nb. Were I to make this decision again, I'd use Caps as my primary modifier, [ as my secondary, effectively giving me four full keyboard maps. Probably overkill but if I were using something like SolidWorks or Illustrator where having both keyboard and mouse access available often, I'd be experimenting with a setup like that -- keeping my right hand always on the mouse, and left for keyboard shortcuts -- biasing all of the shortcut keys to the left-hand region of the keyboard.)
ErgoDox implements a similar system but on the micro-controller level so you don't even have to putz with modifiers and it's cross OS. I don't have one but I would have bought one if I used a desktop more often, simply due to the trackball-feature (effectively letting one use a mouse without leaving the home-row -- a 'must-have' for me).