John Lackey, who won the clinching Game 6 of last year's World Series, didn't fare as well in his latest matchup with St. Louis.
"I felt OK, to be honest," said Lackey. "I got to the pitch count I wanted to get to. I got some things accomplished in the bullpen before the game. I threw my cutter for the first time today. I came out of it healthy and I'll keep moving."
The righty gave up six hits and five runs over five innings, walking two and striking out three.
Shelby Miller wasn't at his best for the Cardinals either, giving up three hits, three walks and three runs over 3 2/3 innings.
"Obviously, he hit it good," Miller said of Pedroia's homer. "He's a good hitter, it's not luck. It was a backed-up curveball, coming inside and I just made a mistake. I should have kept it down a little bit, but he got it no question."
The Cardinals broke out to a 5-2 lead by scoring two in the third and three in the fourth against Lackey.
The big hits were two-run doubles by Descalso and Pete Kozma.
The Red Sox answered with a five-spot against lefty Tyler Lyons in the fifth that was fueled by Napoli's three-run blast and an RBI double off the Green Monster by Xander Bogaerts.
Second baseman Kolten Wong went 3-for-4 with a double and an RBI for the Cardinals.
Up next: Lefty Felix Doubront draws the start in Tuesday's 1:05 p.m. ET contest at the Yankees on MLB.TV. It is one of two meetings this spring between the perennial rivals. Xander Bogaerts, Jackie Bradley Jr., Jonny Gomes, Mike Carp and David Ross are among the position players making the trip.
Ian Browne is a reporter for MLB.com. Read his blog, Brownie Points, and follow him on Twitter @IanMBrowne. This story was not subject to the approval of Major League Baseball or its clubs.