You could be holding it incorrectly for your hands. I suggest you do this, don't put your index fingers on the shoulder buttons, wrap them behind the 3ds and only use them when you have to press the button. That's how I hold my 3ds and don't have much hand cramping issues. If you always have them on the triggers your hands WILL cramp.
This is how I do it as well. It can still take a while for your hands to adjust, but personally I just can't do the trigger thing - so that might be the problem.
I just rest my indexes at the back, and when it's needed, I move my index up to push those buttons. I did see a few after market 3DS "hand grip" controllers - you might wanna check something like that out. I've no experience with them, however, so no idea if they help.