I have carpal tunnel problems severe enough to preclude me using a mouse at work - I alleviate this by using a finger operated trackball (the thumb operated types make it worse, not better) and careful positioning of it so that my hand and wrist are always relaxed when operating my pointing device...
It depends on the HOTAS and its placement.
Firstly, your HOTAS must fit your hand. Before you even think about plugging one into your computer, test both components for "fit". With each controller in turn, start by resting your hand on it with the controller in neutral position. No deflection on the stick, throttle at midpoint. Move your hand around a little without deflecting the control. You're looking for a natural and relaxed hold on the controller that has you "holding" it but not "gripping" it. If you need tension in your fingers or thumb to keep your hand there, that's not the position you're looking for. You want your hand and digits to be touching the controller and as relaxed as possible, exerting little or no pressure on it. If you can find such a position, make a note of it, because it will factor into how you might mount the controllers at your gaming rig. If you can't find any such position for your hands, try other HOTAS models until you find one that you can get as close as possible to this ideal with. Fortunately, you're still likely to have more than one choice at this stage.
Next, with your hands in that relaxed and neutral position on the controller, operate every control on the device and see if any of them present awkwardness or strain. For controls mounted on the stick or throttle you really want them all to be easy and natural actions. For controls on the device bases you want to be able to operate them and return your hand to that neutral position without awkwardness. With the throttle, repeat this test at the two extremes of throttle travel. With the stick, repeat this test at the extremes of each axis (including twist, if present) and with deflections on a combination of axes but ignoring any controls mounted on the stick base - you'll always be returning to neutral/center after taking your hand off the stick to operate those so you don't need to worry about them at extreme deflections.
Finally, "swirl" the controls - moving the stick and throttle through their full range of motion in all axes - VERY SLOWLY. If its not a strain to do this, then you're not going to tense up from long periods of fine control. Indications of problems are if you can't do this particularly slowly while keeping your hand relaxed. You are most likely to encounter issues with a stick twist than other axes on this test but if that's not particularly severe it's not a deal-breaker. On any of the other axes it is a more significant issue.
If you get this far, you'll have one or two candidates for your new HOTAS. When you get over the "OMGSQUEEESHINY!!!!!!!" from unboxing your choice, make sure you mount it such that when your hands are in that relaxed/neutral position on the controllers and you're sitting in your usual position for playing, your arms and shoulders are relaxed. If you don't, all that testing for fit won't help you, the tension will either flow down into your hands or up into your neck and upper back and after a long game session you'll be feeling it. Sit in your usual gaming position with the unconnected HOTAS in your lap and just relax. Put your arms in a neutral relaxed position. Now pick up the controllers, letting their bases dangle, and put your arms back in that relaxed posture. Wherever the bases of the controllers are dangling, that's where you want to mount them. Engineering of chair and desk, I leave as an exercise for the reader
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