Played this for the first time today, incredibly cool game and really impressive for the 3DS... but also ouch oof my wrist hurts now
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I recommend getting a 3DS grip. I got the Hori Monster Hunter grip (I have the New 3DS XL) and its been great. Only other recommendation is to play lying down and putting something like a pillow between you and the 3DS. One hand keeps the balance, other uses the stylus.