Italy are bottom of the tournament table after defeats to Ireland (26-3) and England (47-17), the latter reverse taking its toll on Brunel's strugglers.
Injuries have ravaged his squad, although it was a 'domestic incident' that ruled experienced Toulon prop Martin Castrogiovanni out of action after he received a nasty bite on the nose from a friend's dog last week, prompting hospital treatment, 14 stitches and a course of antibiotics.
"Castro is not training so as to avoid any risk of infection, and is still following a course of antibiotics," said team manager Luigi Troiani.
"He will not be available for the trip to Scotland, but we'll be counting on him returning as soon as possible."
Castrogiovanni is replaced by Dario Chistolini.
In all, six changes were made by French coach Brunel, who has handed full debuts to Michele Visentin and Enrico Bacchin.
It remains to be seen how Italy's reshuffled squad face up to the challenge of the Scots in Edinburgh, but Brunel admitted: "For us, Scotland represent one of our most difficult opponents.
"From 2013 until now we've lost to them, twice by only a point, after we lost control of things at the end of the game.
"They're a side without any particularly strong points, but they have few weak points.
"Against France they were always in contention and against Wales they had a great start. They're difficult opponents, especially at home."
Visentin comes in for injured right wing Leonardo Sarto, while Bacchin replaces injured Andrea Masi at inside centre.
"We have a few changes in the three-quarters because of injuries," added Brunel.
"We started the tournament with (Michele) Campagnaro and Morisi in the centres and after Michele suffered his injury we brought in Masi, who has experience in this position.
"When Masi was also ruled out, we decided to opt for Bacchin, who, from the start of the season, has played alongside Morisi the most. It seems to us the logical choice."
Brunel has kept faith with the half-back partnership of Kelly Haimona and Edoardo Gori for the sixth game in succession, while in the pack Simone Favaro comes off the bench to replace Mauro Bergamasco.
His choice of Haimona over Tomasso Allan augurs well for the New Zealand-born player ahead of this year's World Cup.
"Haimona did well in our first two Tests in November, struggled a bit against South Africa and although he had few chances to make a real difference against Ireland he showed promise against England at Twickenham," said Brunel.
"He was involved in our first try and managed to create a chance for Masi…he showed some good stuff.
"It's a pity he missed some points with the boot but we have to show some faith in him. From here to the World Cup there are only six games, we need some consistency in a key role like fly-half."
In the second row, Joshua Furno steps in to replace injured Marco Bortolami to partner George Biagi, who has secured his third successive start in this year's tournament.
Chistolini's inclusion is one of two changes in the front row with Alberto De Marchi dropping to the bench in place of Matias Aguero.
Italy have beaten Scotland seven times in their previous 22 meetings although the Scots have won their past three meetings.
In the last two, the Scots came away with last-gasp victories – 21-20 in last year's tournament in Rome and 30-29 during a summer test in Pretoria in 2013.
Italy last got the better of Scotland in a 13-6 win at the Stadio Olimpico in 2012.
Luke McLean; Michele Visentin, Luca Morisi, Enrico Bacchin, Giovambattista Venditti; Kelly Haimona, Edoardo Gori; Sergio Parisse (capt), Simone Favaro, Francesco Minto; Joshua Furno, George Biagi; Dario Chistolini, Leonardo Ghiraldini, Matias Aguero.
Replacements: Andrea Manici, Alberto De Marchi, Lorenzo Cittadini, Marco Fuser, Samuela Vunisa, Guglielmo Palazzani, Tommaso Allan, Giulio Bisegni