Manning has started every game for the Colts since 1998, but had a second surgery on his neck in May and was only activated off the team's physically unable to perform (PUP) list on August 29.
On Monday, however, following several media reports, the Colts issued a statement on the four-time MVP's status:
"During the last week, the rate of improvement in Peyton's rehabilitation process slowed. Over the weekend Peyton experienced soreness in his back. It was originally thought to be a normal reaction to his rehabilitation regimen. When the soreness persisted, the Colts medical team decided to initiate diagnostic tests and to consult with a number of specialists around the country who have been involved in Peyton's case from the outset. That process continues. As a result of the most recent development the doctors have decided that Peyton will not practice. His participation therefore, in Sunday's game versus Houston will likely be doubtful. We will update his playing status as required by NFL policy as the week goes on.
"At the conclusion of the diagnostic process, if there are any new developments in the prognosis which we outlined for Peyton at the start of training camp we will report them. As of now Peyton continues to deal with a complicated neurological recovery, the end date of which is unpredictable.
"As was stated at the outset, it serves no useful purpose to speculate about hypothetical outcomes. When and if there are concrete medical facts to report we will do so."
With Manning likely not playing Sunday, that means Kerry Collins will step in to start against the Texans. Collins, who quarterbacked the New York Giants to the Super Bowl after the 2000 season and spent the past five years in Tennessee, had announced his retirement on July 7. He was signed by the Colts on August 24 as insurance in case Manning wasn't ready.
"I feel comfortable with the offense," Collins said. "I feel like I've come a long way in the short time since I've been here. I've really buckled down and grinded on it. Certainly I've got a lot to learn, but as far as my comfort level it's pretty high."
The Colts signed Manning to a five-year, $90 million contract in July -- the long-term deal that was envisioned when the team put its franchise tag on him before the NFL lockout.
Manning has passed for 54,828 yards and 399 touchdowns in 208 consecutive regular season starts and guided the team to a Super Bowl title after the 2006 season.
He has stated that he wouldn't consider playing just to keep his consecutive starts streak alive, saying that he respects football too much to take the field without being ready.
"Obviously, when you look at it it's been an incredible feat," Colts coach Jim Caldwell said. "He's been an ironman. I don't know what other way to put it. He's been there every step of the way. And obviously it's doubtful that he'll play this weekend, but nevertheless, it takes a very unusual individual to put that kind of string together."
Manning also had surgery in March 2010 to relieve pain in his neck caused by a pinched nerve and didn't miss camp. This time around, however, he was unable to meet with team medical personnel because of the lockout.