The Indianapolis Colts head to Mile High to face the Denver Broncos on Thursday in a game between two teams with compromised ground attacks.
The Colts will be without last season's NFL rushing champion Jonathan Taylor, who is dealing with a bad ankle after back-to-back games in which he failed to sparkle.
The Broncos picked up a new running back from the New Orleans Saints' practice squad this week after losing starter Javonte Williams for the rest of the year with a knee injury.
It could mean the game turns into a battle between veteran QBs Matt Ryan and Russell Wilson, both still yet to really find their passing rhythm after switching teams this past offseason.
Indianapolis Colts @ Denver Broncos
Empower Field at Mile High, Denver
01:15, Friday 7th October 2022
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Sky Sports NFL, NFL Game Pass & bet365 Sports Live Streaming
IND Colts 6/4 , DEN Broncos 10/17
A prolonged absence for Williams, believed to have torn his ACL and LCL, is really bad news for the Broncos and it was no surprise to see them act swiftly to sign up Latavius Murray.
Murray scored a touchdown for the Saints in their 28-25 NFL London loss to the Minnesota Vikings on Sunday, gaining 57 yards on 11 carries.
He probably won't figure much - if at all - against the Colts as he learns a new playbook, with others needed to pick up the slack.
Second-stringer Melvin Gordon was benched in the second quarter of last week's loss to the Las Vegas Raiders after he coughed up the fumble that Amik Robertson returned 68 yards for a touchdown.
Mike Boone, previously third on the depth chart, got his first three carries of the season against the Raiders, but Williams' load will have to be shared around.
Indianapolis' running game hasn't hit its stride in 2022, with the Colts averaging just 87.8 yards per game to rank 26th in the NFL, after establishing the league's second-ranked rush offense last year.
The offensive line has struggled mightily through the first few weeks, giving up 15 sacks and failing open the sort of holes between the tackles that Taylor exploited last year.
With Taylor out, Nyheim Hines should see more snaps, but at 5-9 and just 196 pounds he will still be regarded as primarily a receiving back for third-down usage.
Deon Jackson and Phillip Lindsay, who had a good career going in Denver before his production dropped, are in contention to replace Taylor on first and second downs.
Lindsay still has a healthy career average of 4.5 yards per carry, but averaged just 2.8 on 88 rushing attempts last season.
Expect both offensive coordinators to put the gameplan in the hands of their respective, highly-paid, quarterbacks with Wilson just starting to show signs of finding his feet within Nathaniel Hackett's system.
The ex-Seattle Seahawks star threw for 237 yards and two TDs last week while compiling a quarterback rating of 124.9.
Colts counterpart Ryan is coming off his best game for Indy, despite their 24-17 home defeat to Tennessee last week.
The former Atlanta Falcons star threw for 356 yards and two TDs with one pick, recording a 73% completion rate against the Titans.
And Ryan catches a break this week with the news that Broncos pass rusher Randy Gregory misses out through injury, leaving linebacker Bradley Chubb, who has registered three sacks this season, as the man to avoid.
The star of Denver's defence in 2022 has been cornerback Patrick Surtain, who had a career-high eight tackles in Week 4 when he held Las Vegas' WR1 Davante Adams in check.
They match up well as a unit to Indianapolis right now, as the Broncos' strength has been in defending the passing game - for which they rank fifth overall - while stopping the rush has been a relative weakness so far.
In contrast, the Colts have the sixth-best run defence and rank tenth against the pass, although they are tied 24th in scoring defence.
Both teams have struggled in the red zone, but the Broncos' defence has been able to keep them in games when their offense has misfired, allowing the second-fewest passing touchdowns and the sixth-fewest rushing touchdowns in 2022.
Denver, who are 8-3 all-time at home in the series, appear to be worthy favourites for this one and the -3.5 point Spread may not be beyond their powers to cover.