I think Gorn and jnuts are both correct.
I agree with Gorn that improved technique increases relaxation, decreases muscle over-excursion, which results in decreased lactic acid buildup in the arm/hand muscles... which results in less and perhaps even no cramping. Furthermore, tendons begin to travel in more direct, anatomically correct pathways from origin to insertion across joints, thus allowing those wrist and finger joints to act only within their designed axis’.... In other words, less stress on the joints, and less chance to develop arthritis or inflammation that can lead to deformity and/or syndromes such Carpal Tunnel in the wrist.
That said, jnuts is also correct in saying different players will respond to different instruments from an ergonomic perspective. As much as I’ve wanted to play one, I just could not get without left wrist pain when playing a Warwick, whereas I never have any pain playing my Fenders, Sadowsky, MTD, or Smith.
Finally - I agree with pcake and others who suggest that neck thickness (front to back) is a huge factor in hand fatigue. Despite having average-sized man-hands and pretty well-developed technique, I just can’t get along with super-thin necks - I just seem to like ‘em on the chunky side.
YMMV