The quarter-final exit at the 2011 World Cup was sandwiched between two successive Six Nations reverses, with the latest loss coming courtesy of a last-gasp penalty from Leigh Halfpenny and the previous defeat featuring Mike Phillip's controversial winning try.
O'Brien admits the pain of those setbacks still lingers and will act as an extra driving force as Ireland look for a repeat of their 2009 Grand Slam triumph at the Millennium Stadium.
"Wales has become a championship-defining match," said O'Brien, who will start Saturday's fixture on the openside flank.
"You can't win a Grand Slam on the first day, but you can lose one if you don't make a good start.
"There's a bit of hurt on our part after losing the last three and we want to put that right.
"Things didn't go our way last year, which was unfortunate because we played so well at times during the game. But we didn't play for the full 80 minutes, which is what we're looking to do this time.
"Wales may have lost seven in a row, but I don't think they'll be nervous at all.
"It's obviously a massive game for us. Wales are very tough opposition. The set-piece and breakdown will be massive."
Leinster star O'Brien insists clubmate Jonny Sexton's decision to move to France next season won't have any impact whatsoever on the mood within the Ireland camp.
O'Brien, whose own contract expires next year, supports Sexton's decision but insists he doesn't envisage many other Irish internationals following him to the Top 14.
"It's Jonny's decision and I'd back him wherever he goes. He's a good friend who has done a lot for Leinster since being in the academy," added O'Brien.
"We're a big club. People come and go and I'm sure it will happen again at some stage.
"I don't think there are too many lads who will follow suit. People are happy where they are at the moment as the provinces are doing well.
"The IRFU look after players pretty well and that's a factor in any decision.
"When the time comes, if clubs are after you, you're going to take into consideration what's on offer. You've only so long in the game and you have to look after yourself. They're tough decisions to make, but you live and die by them."