England boss Martin Johnson has described Jonny Wilkinson's latest cruel injury setback as "very upsetting".
Wilkinson will not be in England contention again until the RBS 6 Nations Championship later this season.
A dislocated knee-cap suffered while on Guinness Premiership duty for Newcastle against Gloucester nine days ago means the Falcons fly-half faces a probable four-month recovery period.
He underwent successful surgery last week, but it leaves Johnson without England's record points-scorer for Twickenham clashes against the Pacific Islands, Australia, South Africa and New Zealand next month.
Danny Cipriani, who ended last season's Six Nations as England fly-half, is likely to be promoted from the England Saxons squad to replace Wilkinson in Johnson's 32-man elite group.
Cipriani began his comeback from an horrific ankle injury just 24 hours after Wilkinson was hurt.
Johnson said: "It's great for Danny to be back. I spoke to him on the Monday after he had hurt himself and he was already talking about getting back.
"We have been in contact the whole way with him, as we would do with any injured player.
"Danny has worked incredibly hard, as have the people around him.
"But the day before he comes back, Jonny gets hurt.
"It is very upsetting when you see that for a guy who has had a lot of injuries during the last four or five years to get hurt again.
"But he's a strong guy. He's had surgery, which has gone well, and we look forward to him coming back.
"The number 10 position is very competitive - there is some good depth there.
"Jonny is obviously the most experienced guy there, but Toby Flood is playing well at Leicester, Olly Barkley can play 10 and 12, so can Shane Geraghty, and Danny's back as well, with Andy Goode and Ryan Lamb in the Saxons."
England's big November examinations might be against the Tri-Nations heavyweights, but Johnson has warned of the Pacific Islands' danger in his first match as team manager.
"With the teams we are playing against, you want to keep the ball away from them, which starts in the first game against the Pacific Islands," Johnson told the http://www.rfu.com podcast.
"Those guys will look to play off poor kicks, from broken play and turnover ball. They will kill you if you do that.
"They don't play that many games. We know the players they've got, but you have less to go on in terms of the style they will play.
"We do know they've got some great athletes in players like (Seilala) Mapusua and (Sailosi) Tagicakibau, who can really run the ball and are powerful and strong.
"They will want to come and play. They will feel they've got nothing to lose in a way, coming to Twickenham.
"They will be dangerous - it is not a warm-up game, it is a full-on Test match."