I know I'm late to the party, but perhaps I have useful information for future reference for anyone needing it.
I used to live in that area. 160 is bad enough in a small sports car. I think there's some sort of height or weight restriction for big trucks somewhere between Branson and Gainsville also. Taller 5th wheels might want to take note.
U.S. 60 is by far the best east-west route in the area. It's easily worth the extra 30 miles or so up to Springfield to hop on that.
Those ancient bridges crossing from Missouri into Illinois and then into Kentucky (all on U.S. 60) are also something to avoid unless you just really want to do some sight-seeing. Once in Kentucky, the roads (60 and/or some other state road that runs parallel to it) are possibly worse and narrower than 160 in Missouri, just not as hilly.
It's few miles out of the way to head up into Cairo on I-57 then meander across to Metropolis on state roads then to points beyond on I-24. Out of the way a little, but totally worth it if you don't like uneven narrow roads.
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Trailer:2019 Cherokee Wolfpup 16BHS
Truck: 2010 Toyota Tundra 4.6L
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