SAN FRANCISCO – Delivering his eighth pitch, Reds right-hander Johnny Cueto bounded off the mound in pain, and the complexion of Game 1 of this National League Division Series changed.

In a matchup of aces, the Reds were suddenly piecing together a stopgap plan, while the Giants still had theirs, Matt Cain, in place.

But until the ninth inning, against a succession of Reds relievers and one nemesis – starter Mat Latos, salvaging the middle innings – the Giants had only Buster Posey's solo home run to show for a barrage of hard-hit balls, while the Reds became the first team to score an earned run against Cain in the postseason.

Following their 5-2 loss Saturday night, the Giants, who did not lose a Game 1 in their run to a World Series title two years ago, now face that deficit with only tonight's game at AT&T Park before the series shifts to Cincinnati for good.

"It's a big game," right fielder Hunter Pence said bluntly. "It's a real big game. We've got to get back out there and get after it, hit some balls to find some holes."

The Giants brought the tying run to the plate in the ninth with one out against Reds closer Aroldis Chapman. But Pablo Sandoval popped out and, after a wild pitch brought Joaquin Arias in from third, Posey, amid chants of "M-V-P" from the announced sellout crowd of 43,492 at AT&T Park, struck out swinging at a high fastball.

The Giants now must win at least twice at Great American Ballpark to claim the series. It's unclear whom they will face in Game 3. It was slated to be Latos, but shortly after Cueto left the game because of back spasms in the first, Latos stabilized the game for the Reds.

As Cueto delivered a pitch to Marco Scutaro, Cueto bounced off the mound grimacing and shaking his head. Reds trainers came to the mound to check on him, and Cueto flipped the ball to manager Dusty Baker and walked off the field in obvious discomfort.

Right-hander Sam LeCure finished the inning, and Latos came on in the third for his first relief appearance in the majors – and his first at any level since 2009 in Class A.

"That was a little bit of a curveball, for both teams," said Pence, who added he prepared for the game by studying Cueto and the Reds' bullpen but had faced Latos before. "It's unfortunate that Cueto got hurt. He's a great pitcher."

While hitters prepare for the scheduled starter, Giants manager Bruce Bochy said, "We have all the information on the relievers, and Latos, who came in. They pitched well. It's a good staff."

Latos allowed only Posey's homer in the sixth and has a 1.72 ERA in 47 career innings at AT&T Park.

Cain, meanwhile, had his streak of postseason innings without an earned run allowed snapped at 23 1/3 in the third inning, when Brandon Phillips hit a mistake two-strike breaking ball into the seats in left for a two-run homer.

Jay Bruce then homered to lead off the fourth over the high wall in right-center, extending his mastery of Cain, against whom he is 8 for 15 in his career.

"The pitch to Bruce wasn't too terrible, but the hanging breaking ball to Phillips is just something that you don't want to happen in a big-game situation like this," Cain said. "The hanging breaking balls in these games, they always hurt a little bit more."

As did some of the balls the Giants hit that did not fall. Reds left fielder Ryan Ludwick dived to rob Brandon Belt of a flare hit in the sixth and reached up on a dead retreat to snag a liner by Scutaro in the seventh.

Belt's liner in the fourth with Pence on first appeared headed down the right-field line until Joey Votto reached up, speared it and easily doubled up Pence as Belt put both hands on his helmet in disbelief.

Cain, who was lifted for a pinch hitter in the fifth as he was scheduled to lead off, said the Giants will keep level heads despite falling behind in the quick best-of-five series.

"It'll be fine," Cain said. "These guys show what they're made of, and we'll find out what tomorrow brings."

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