For the Irish to stay in contention for the championship, they will need to beat Italy - something that surprisingly was beyond them last season when they lost 22-15 in Rome. That was Ireland's first Six Nations defeat to the Azzurri in 14 meetings and proved to be the last match for head coach Declan Kidney.
"We can use it as a bit of a spur on," Ireland lock Devin Toner said. "No one wants to feel like that again."
O'Driscoll will beat the test appearance record he held jointly with former Australia halfback George Gregan. Eight matches for the British and Irish Lions are included in O'Driscoll's total.
"The head is still willing, but the body not as much," O'Driscoll said. "I want to get out of the game relatively unscathed. Now is the time to do it. I'm not bored of answering questions or signing autographs or doing pictures; I could go on another dozen years doing all that. It's simply that age does catch up on you and physically you can't do what younger guys can do."
Jonathan Sexton has recovered from a thumb ligament injury to keep his place at first five-eighth. The only change from the team that lost 13-10 to England at Twickenham in Round 3 sees Iain Henderson starting as blindside flanker, replacing the injured Peter O'Mahony.
With three straight losses, the most recent to Scotland, the Italians are heading for another wooden spoon. And their chances of getting anything from their trip to Dublin haven't been helped by coach Jacques Brunel's decision to rest his one world-class player, captain and No8 Sergio Parisse, who is nursing a calf injury.
Appearing to be saving some players for the finale at home against England, Brunel has made some makeshift choices: A lock (Joshua Furno) will make only his second start as a flanker, a flanker (Robert Barbieri) will make his first start at No8 in the championship, and Wales-based halfback Tito Tebaldi has been summoned for his first test in almost two years. "Ireland are certainly a better squad than last year," Brunel said. "But we have to remember that we beat them barely a year ago in Rome and in a rather convincing fashion."