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The visit of third-place City to Old Trafford always generates a heated atmosphere, and it is certain to do so on Saturday with both teams in contention for the title for the first time in a generation.
That pressure could intimidate a United squad aiming to recover from last week's shock 2-1 loss at relegation contender Wolverhampton Wanderers, but midfielder Darren Fletcher wants it to inspire his teammates.
"This is when the big games come, the matches that ultimately win you trophies," Fletcher said. "We enjoy big games here and this club is all about performing and rising to those challenges."
United's players have mostly done so this season but were unable to rouse themselves against a defensively tenacious Wolves side.
At least the motivation will be there against City, who are five points behind United having played one game more.
Second-place Arsenal, four points off the lead, will expect victory against visiting Wolves, while Tottenham can take fourth place for two days if they win at Sunderland since current occupant Chelsea is at Fulham in Monday's only match.
"We've got to go to Liverpool, Chelsea and Arsenal and we play Manchester City this weekend," Fletcher said. "We know all of that lies ahead of us and we've never naively thought that the league is over. There is a lot of hard work to come, lots of big games and plenty of twists and turns I'm sure.
"You have got to earn the title. Nobody is going to give you the trophy lightly."
United will be without central defender Rio Ferdinand after straining his calf warming up for the 2-1 defeat by Wolves, giving City and star striker Carlos Tevez real hope of improving upon a record of just one goal in five matches this season against the other teams in the top five.
"When you are on a good run like United were on and you lose, everything becomes harder," City defender Kolo Toure said. "It shakes your confidence. Maybe that can happen to them but derbies are different games."
City have won just once at Old Trafford since 1974, but drew 0-0 against United earlier this season and drew 0-0 at Tottenham and Arsenal.
Arsenal get the chance to show how things should be done against Wolves at Emirates Stadium, but Wolves are on a high after making it off the bottom of the table last weekend and have beaten United, Chelsea and City this season.
Like United, Chelsea also need to get over a surprise loss following Liverpool's 1-0 win at Stamford Bridge. That loss dampened the enthusiasm generated by the British-record signing of Fernando Torres and left Chelsea with an uncharacteristically weak record of six defeats from its past 15 Premier League matches.
Also on Saturday, Stoke are at Birmingham, Newcastle are at Blackburn, Aston Villa are at Blackpool, Wigan are at Liverpool and West Ham are at West Bromwich Albion.
Bolton host Everton on Sunday.
