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3. A short-handed running back room

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The absence of Pacheco is a blow, considering Buffalo allows 4.7 yards per rush this season — the fourth-highest rate in the NFL. The Chiefs’ offense will still want to establish a presence on the ground.

Clyde Edwards-Helaire will be the primary ball carrier; he hasn’t seen more than three carries in a game since Week 3. I believe the team will opt to elevate rookie Deneric Prince from the practice squad again and mix him in too.

Veteran Jerick McKinnon should be reserved for pass downs; he has not looked as explosive on run plays as he has in past years.

Watch for wide receiver Kadarius Toney to be used from the backfield, getting handoffs from shotgun like he did against the Philadelphia Eagles.

4. Matching up with Bills’ pass catchers

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Wide receiver Stefon Diggs is the alpha male in the Buffalo receiving corps. He will draw the attention of cornerback L’Jarius Sneed, but there are other intriguing matchups to consider.

Typically aligned on the outside, wide receiver Gabe Davis is a big-bodied, downfield threat (as Chiefs fans remember). The defense will want to match him up with either cornerback Jaylen Watson or Joshua Williams, avoiding the size mismatch between Davis and Trent McDuffie.

McDuffie will have a challenge of his own in the slot: Khalil Shakir, a second-year wideout who can make big plays after the catch.

After starting the year with more two-tight end sets, Buffalo has shifted to 11 personnel with Dawson Knox hurt. Rookie Dalton Kincaid has caught at least five passes in each of the last six games. Safety Justin Reid will be tested at all levels of the field, covering Kincaid’s athleticism.

5. The return of Nick Bolton

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With running back Jerick McKinnon designated as questionable for the game, starting running back Isiah Pacheco is trending for more and more touches. It’s deserving — and many times, it’s what the offense has needed to get going.

There is, however, a lot of season left for a position group that seems as thin as it ever has during the last few years. Running back Clyde Edwards-Helaire has been running hard — but not effectively enough to spell Pacheco. That’s why I believe running back La’Mical Perine needs more snaps — sooner rather than later.

That could happen against the Packers, who have faced the third-most rushing attempts per game — and have allowed the eighth-highest yards per rush (4.4).