That 26-19 defeat - and injuries to five key players - has left England in a state of disarray.
And matters could be compounded if captain Phil Vickery fails to recover in time from a calf muscle injury suffered during training.
If Vickery misses out - a decision is likely later on Saturday - then Bath's Matt Stevens will deputise at tighthead prop with his club colleague Steve Borthwick, not Jonny Wilkinson, probably taking over as skipper.
England's four previous Six Nations trips to Rome have harvested 185 points and a 100% winning record, but the Azzurri will fancy their chances of halting that sequence, especially as their opponents have lost Mike Tindall, David Strettle, Andrew Sheridan, Lewis Moody and Tom Rees.
Wells said: "I think Italy went through the Six Nations last year and gave everybody a hard time to some degree or another.
"They made it very difficult for England to do anything other than scrape a victory at Twickenham.
"There is a massive amount of experience in the Italian side, and part of the challenge is playing against mentally and physically tough opposition, on their own pitch, who are going to want to knock our blocks off.
"Italy come from a scrummaging, driving, mauling, brawling background, and we know we are going to a place where it is becoming harder and harder to get wins.
"There is no point going there with our heads down. We need a really positive environment and a positive vibe from within."
Key to England's victory bid could be how they use juggernaut wing Lesley Vainikolo.
The former Bradford Bulls rugby league star was chronically under-used against Wales, and it is vital England utilise his power and pace at every given opportunity.
England defence coach Mike Ford added: "I am really looking forward to seeing him pop up here, there and everywhere. We are going there with a very positive attitude."