As has been stated by a few here already, the .38 special loaded mildly as would be appropriate for squirrels or other small game, is a probably a safer load than a .22LR. A wadcutter, which is ideal for punching a big hole with no meat damage, like a hi-vel .22 round would possibly create depending on the bullet design, is ideal. That .38 will travel less than half the distance of a .22, so get a load in the 750fps range with a WC bullet and use it and feel comfortable with it. The real danger with shooting up, as in squirel hunting, is not knowing who is a mile away, not 1-200 yards. Sure it's possible there are people/property withing a couple hundred yards, but it's far more likely you won't know about it if it's a mile away. If you zero a Speer 148gr HBWC@750fps at 25yards, you'll be able to hit a 1" target out to about 32 yards, which is about as far away as most folks can hit a 1" target with a open sight revolver. At a quarter mile, this load is 88 FEET below the line of sight. I realize this does not truly represent shooting up into a tree, but it gives you an idea of how much less likely it is to land somewhere you don't want it to than a .22LR
At 800 yards, it is 1166 FEET below the line of sight.