No. The max g-force on launch is 4g, which is very tolerable with minimal training, especially when in the optimal sitting position (basically reclined on your back).

I’ve flown up to 7g and it’s never panful, just requires focus and proper breathing and muscle clenching technique to not start to experience greying out of vision or loss of consciousness. Another factor is to avoid abrupt onset of Gs, which the astronauts shouldn’t have a problem with. I wore a G-suit but people can handle Gs without them just fine, like the Blue Angels pilots.

The other factor you may be thinking of is pressurization changes, but the maximum cabin altitude of the Orion will be about 8000’ feet, which will give about a 12 psi difference between the inside and outside of the capsule when in a vacuum. The change from sea level to that altitude is 8000’ feet and just over 2psi, but the automatic pressurization systems of aircraft and spacecraft are set up in a way to make that change gradually for occupant safety. It wouldn’t increase to that altitude as fast as the actual spacecraft climbed to 8000 feet, as that would indeed be very uncomfortable.

Besides those considerations, nothing else about rapid altitude or velocity changes would be painful, as the occupants are not exposed to any forces besides internal acceleration and pressurization changes.