I have a couple of ways that I open Spyderco knives. When I use both the thumb and index finger, I hold the blade by the hole and flick the handle downward to open the knife. Folks these days call that a "Spyderdrop" even though people have been doing the same thing with Buck knives since the '60s or earlier.
The thumb only method does apply a bit of lateral force to the blade, but it does when using thumbstuds as well. My thumbs are long enough and limber enough that I snag the edge of the hole with my thumbnail rather than the pad of my thumb, so even if the edge of the hole is fairly sharp, it is not uncomfortable for me. Thumbstuds are often too close to the handle for me to snag with my thumbnail, so I end up using the pad of my thumb, which I find less comfortable. It depends on what you are used to.
Unlike Kaizen, I have read of people finding Spyderco thumb holes uncomfortable, some even being sharp enough to cut an unwary thumb. A piece of sandpaper will fix that in a jiffy.