After being spurned during the offseason by New England Patriots offensive coordinator Josh McDaniels for the then-vacant head coach position in Indianapolis, Colts general manager Chris Ballard provided a comment to fuel future matchups.
"The rivalry is back on," Ballard said on Feb. 7 as he walked away from the podium.
The rivalry between the two teams peaked during numerous Peyton Manning-Tom Brady showdowns. And the high-profile competition between the two teams drew further national attention on the heels of the 2014 AFC Conference Championship game, which produced the Deflategate scandal and later a four-game suspension for Brady in 2016.
While there are off-field matters to add fire to the matchup, the players still have a game to play, of course.
So, with that in mind, here are five areas to watch Thursday night at 8:20 p.m. ET (watch the game on FOX, NFL Network, or streaming on Amazon Prime Video):
1. Is it really a rivalry if recent contests produced one-sided results?
Let's start with the obvious because the win-loss record doesn't lie.
The Patriots have dominated this matchup in recent years by winning seven straight games, including the postseason, against the Colts with an average margin of victory of 19 points. The last time the Colts defeated the Patriots occurred in Week 10 of the 2010 season in Indy, and the Colts haven't won in New England since 2006.
Colts quarterback Andrew Luck is 0-5 on his career, including the playoffs, against the Patriots and has totaled more losses and interceptions (10) against New England than any other opponent. The glare of a national audience also doesn't bode well for Luck, who is 7-8 on his career in prime-time games, including going 1-5 in the last six.
Brady also provides a historical sidebar to monitor. The Patriots quarterback enters Week 5 with 497 career touchdown passes, which currently ranks third all-time and one ahead of New Orleans Saints signal-caller Drew Brees. With three TDs Thursday night, Brady can join an exclusive 500 Club with Peyton Manning (539) and Hall of Famer Brett Favre (508).
2. How effective will the Colts' aerial attack without T.Y Hilton?
Hilton (hamstring, chest) did not participate in the Colts' walkthrough practices Monday and Tuesday and was officially ruled out Wednesday.
While Colts will be without Hilton, there shouldn't be a need to panic when considering what Luck has done with the other receivers.
Hilton leads the Colts with 21 catches for 294 yards on 38 targets, but Luck's completion percentage is just 55.3 when compared to a combined 75.9 when throwing to wide receivers Ryan Grant, Chester Rogers, Zach Pascal and Marcus Johnson.
The Colts will also be missing tight end Jack Doyle (hip), but Eric Ebron (knee) is good to go. Ebron leads the Colts with three receiving touchdowns.
3. What will Julian Edelman do?
The Patriots enter Week 5 ranked 22nd in the league in passing, but Brady and the offense get a boost with the return of wide receiver Julian Edelman, who served a four-game suspension to start the season.
How much does Edelman's role as a reliable slot receiver mean to Brady and the Patriots' offense?
Since 2013, the Patriots are 46-9 with Edelman in the lineup, but 19-10 without him. Before missing the 2017 season with a torn ACL, Edelman proved himself as a major spark within the offense, totaling the most receptions and yards receiving for Brady from 2013 to 2016. During the 2016 season, Edelman led the offense with 98 receptions for 1,106 yards receiving on a head-turning 158 targets.
While the Patriots should get more productivity on the outside from wide receiver Josh Gordon, who made his debut last week, going forward, Edelman's presence goes beyond his individual statistics.
Edelman's ability to work routes underneath will free up defensive coverage on tight end Rob Gronkowski, who has been consistently mugged by double teams this season. Gronkowski (ankle) didn't practice Monday or Tuesday, but the injury is minor and he is considered day to day.
4. Can the Colts put together a run game?
Indianapolis hasn't succeeded in establishing the running game so far and currently ranks 29th in the league, averaging 72 yards per game.
But not having running back Marlon Mack, who has been dealing with a hamstring injury, the past two games certainly doesn't help. Mack will miss another game Thursday, so the Colts once again will rely on rookies Nyheim Hines and Jordan Wilkins.
The matchup suggests the Colts could have success when considering the Patriots enter Week 5 ranked 26th in the league against the run, allowing 121.5 yards per game. In New England's two losses, they allowed 104 total yards rushing to the Jacksonville Jaguars in Week 2 and 159 yards to the Detroit Lions in Week 3.
The Colts rushed for 104 yards as a team in their lone win against the Washington Redskins in Week 2, while failing to top 75 yards in three losses.
5. Can the Patriots use Thursday night to jump-start the season?
Different season, but the Patriots maintain the status quo of starting slow.
Since 2016, New England is 7-5 in the first four weeks. Something always happens, however, from Weeks 5-17 to energize the team to finish strong, evidenced by a 22-2 record with just one loss at home during that span.
The Patriots have started 2-2 or worse a total of seven times in the Tom Brady era, but shook off the sluggish starts by winning the Super Bowl in three of the six previous instances.