The Indianapolis Colts thought they'd suffered a big blow when they ruled their four-time MVP quarterback out for the season opener. Now they may have lost Peyton Manning for the entire season.

Manning underwent more neck surgery Thursday, his third procedure in 19 months, and his return this season is uncertain.

Losing Manning for any stretch of time is something the Colts would love to avoid, and it's certain to throw the race for the AFC South wide open. Manning hasn't missed a game in 14 NFL seasons, with 227 consecutive starts, including the postseason.

"Rehabilitation from such surgery is typically an involved process," the team said in a statement, calling the procedure "uneventful."

The Colts said there would be "no estimation of a return date at this time. We will keep Peyton on the active roster until we have a clear picture of his recovery process."

Team owner Jim Irsay tweeted that the 35-year-old Manning would be out "awhile."

The Colts could have put Manning on injured reserve to open a roster spot, but it would have meant him not playing at all during a season that ends with a Super Bowl at Lucas Oil Stadium in downtown Indianapolis.

Manning underwent an anterior fusion procedure to treat a nerve problem that still bothered him after his previous surgery, on May 23. Such a procedure usually involves making an incision in the front of the neck, removing soft disk tissue between the vertebrae and fusing the bones together with a graft. The goal is to ease pain or address a disk problem.

Recovery typically takes at least eight to 10 weeks, said Dr. Victor Khabie, co-chief of the Orthopedics and Spine Institute at Northern Westchester Hospital in New York. He did not treat Manning, but is familiar with the procedure and how athletes recover from it.

"It could be season-ending, seeing the piggybacking off of another surgery," Khabie said. "But the athletes I've known over the years, I never count out because they are such great competitors and such great healers."

If Manning recovered in 10 weeks, he could be back for a Nov. 13 game against Jacksonville, the week before the Colts have a bye.

Dr. Andrew Hecht, director of spine surgery at Mount Sinai School of Medicine in New York, doesn't believe the injury will prematurely end Manning's career.

Hecht, who works with the New York Jets and New York Islanders, said the biggest risk is healing. He said it typically takes three months for the fusion to occur, though some people heal faster.

"The odds are that he'll end his career when he wants to end his career," Hecht said.

Manning, who signed a five-year, $90 million contract in July, also had neck surgery in February 2010. This, however, has been one of the most frustrating offseasons of his career.

The 4½-month lockout prevented him from working out with team trainers and he couldn't negotiate a new contract with the Colts during that time. He started training camp on the physically unable to perform list, which prevented him from working out with teammates until Aug. 29.

With Manning, the Colts have been a perennial Super Bowl contender. Without him, the most dominant team in the AFC South since its creation faces a daunting challenge: trying to become the first team to play a Super Bowl in its home stadium without having Manning behind center for possibly the entire season.

Since being taken with the No. 1 overall pick in 1998, Manning has led the Colts to 11 playoff appearances, 11 double-digit winning seasons, eight division crowns, two AFC titles and a Super Bowl championship.

The biggest question is when he will return.

"None of us know," coach Jim Caldwell. "It is a little bit in flux at this point."

Khabie said the fact that Manning has had neck surgery three times in such a short period is reason for concern.

If Manning does return this season, he will also be playing behind a revamped line that has three new starters and a fourth playing a new position. Longtime right tackle Ryan Diem has moved inside to guard.

The player who can empathize most with Manning is running back Joseph Addai, who injured a nerve in his left shoulder Oct. 17 against Washington, then missed the next eight games.

There were times, Addai recalled, he would wake up during the night with sudden pain. There were other times he couldn't hold a microphone or the ball would drop out of his hands with a slight bump.

Addai figured the ensuing bye week would give him enough time to heal, but it took more than two months to get back into a game and he still didn't feel 100 percent until this season.

"After a while it came back, but you don't really know when it's going to come back," Addai said. "It's frustrating."

Addai said Manning asked him about the experience, something the two discussed at length since players reported to camp July 31.

Addai said he's worried about playing the Texans without Manning.

"You know how important Peyton is," Addai said. "I think everybody has to step it up."

Kerry Collins will replace Manning in the lineup Sunday, making him the first Colts quarterback other than Manning to start a game since Jim Harbaugh — now the head coach of the San Francisco 49ers — on Dec. 21, 1997.

The only other time Manning has missed a regular-season snap because of injury was in 2001 against Miami. Backup Mark Rypien fumbled. The Dolphins recovered and drove 59 yards for the winning score. Manning returned on the next series with a bloody mouth. He was later diagnosed with a hairline fracture in his jaw.

Manning, who rarely misses a snap even at practice, has occasionally been sidelined during the preseason.

He sat out one week of training camp in 1998 before signing his rookie contract. A decade later, he missed all of training camp after having surgery twice to remove an infected bursa sac from his left knee. He also missed some practices after injuring his knee during a preseason game against Minnesota in 2001.