Joe Schmidt had already lost CJ Stander, Devin Toner and Garry Ringrose from the team beaten 32-20 by England in Dublin last weekend.
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Munster Rugby centre Chris Farrell is also brought back instead of Leinster's Garry Ringrose, who picked up an injury against England.
"He just got a dead leg and it hasn't recovered sufficiently so we're just gonna have to forge ahead".
Replacements: Sean Cronin, Dave Kilcoyne, Andrew Porter, Ultan Dillane, Josh van der Flier, John Cooney, Joey Carbery, Jordan Larmour.
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"It's just a bit of aggravation after having a knock", Schmidt said of Henshaw. He stepped in only once a year ago and got man of the match.
'It does make it hard; the problem is he maybe could have played, but if you get another bump on it, it debilitates you quickly, and then you have to make another change'.
"You've got Chris Farrell sitting in the wings, massively motivated to do his best". It's a great opportunity to get him in.
This is Schmidt's last Six Nations in charge of Ireland before he stands down after this year's World Cup in Japan.
"That hurt for sure and there weren't too many guys who slept well on Saturday night".
IRELAND: Rob Kearney; Keith Earls, Chris Farrell, Bundee Aki, Jacob Stockdale; Johnny Sexton, Conor Murray; Cian Healy, Rory Best (capt), Tadhg Furlong; Quinn Roux, James Ryan; Peter O'Mahony, Seán O'Brien, Jack Conan.