I do a lot of hand sewing. If my hand begins to hurt while appliquing, I change needles, usually switching to a straw needle. My hand rarely hurts when I hand quilt, unless I prick myself. :(
My hands usually don't hurt, but my wrist will bother me from time to time. I blame the computer for that - I use one all day at work. If it hurts a lot I use a wrist brace, even wearing it to bed. It keeps the wrist straight and helps ease the pain.