I wish I liked the MX but I'm not sure if I have bigger than average hands (I don't think so by much!).. I believe the issue is that with putting my hand on the MX mouse the only contact I have with the desk is my wrist and that puts pressure on my wrist.

However with a mouse that doesn't have the thumb support like the MX does, my thumb and left side of my (right) hand distributes more pressure along my hand and down to including my wrist so it distributes the pressure more evenly.

It's also not necessarily just pain but ergonomic uncomfortable in a way that was super distracting, like warning signs that if I kept it up then I'll eventually be in pain.