Senate Majority Leader Harry Reid’s ability to cut key deals and pass legislation over the protests of Republicans is being put to the test these days, making advancing even run-of-the-mill bills a significant political lift.

The Nevada Democrat’s challenges are many: Difficult midterm elections are closing in, the GOP has launched a successful messaging operation against his party’s initiatives, and many Democrats are wary of tough votes after a year of twisting on health care reform, lawmakers and aides said.

That, in turn, is forcing Reid, who also is up for re-election this year, to offer concessions to move legislation extending popular tax cuts and unemployment insurance.

One senior Senate Democratic aide acknowledged that Reid and other Democratic leaders have “very little room to bargain” given that Senators from both parties are tapping into voter frustration about “spending that is out of control, deficits mounting and politicians in Washington who seem tone deaf to that issue.”

Because of that, the aide said, “We may be in a position where in order to attract Republican votes now, we may need to make deeper concessions than previously. … But deals are still there to be made. Harry Reid is still a consummate deal-maker.”

But the fact that a dozen Democrats joined Republicans on Wednesday to defeat a watered-down version of a tax extender bill that passed in March had the GOP crowing.

“Twelve Democrats joining all of us, that’s a significant signal,” Senate Republican Conference Chairman Lamar Alexander (Tenn.) said.

Alexander argued that while Reid in the past had been able to rely on a handful of GOP moderates to get him to the 60-vote threshold to beat back a filibuster, the Democratic leader is finding it increasingly difficult to use “a shooting gallery approach and just picking off one or two of us.”

Republican Policy Committee Chairman John Thune (S.D.) said the public and Senators alike have “debt fatigue.” He said the issue has become too big of a concern and that Reid can no longer rely on sweeteners and arm-twisting to pass pricey legislation.

“Debt fatigue is really effecting this president’s and this leadership’s ability to get any more of their agenda through, and it’s playing out with this legislation on the floor,” Thune said.

Sen. Claire McCaskill (D-Mo.) said centrists like her are feeling “some pressure because we all know it’s time to start being serious about trying to pay for everything.”

She predicted, “I think it’s going to be a lot harder to pass anything that spends lots of money that’s not paid for.”

Sen. Mark Begich (D-Alaska) agreed, saying, “All the money ones are harder asks for me.” He noted that the debate over deficits within the Democratic Party has just begun: “What you’re seeing is the evolution of this debate, really right in front of you.”

One Democratic lawmaker said Reid still has pull in the caucus for things he really wants, and suggested that the Majority Leader did not push moderates on Wednesday to back the extenders bill.

Instead, the lawmaker said, the vote was intended to show liberals that centrists were unwilling to write blank checks.

On a recent vote that was important to Reid, this Senator waited until it was clear the Democrat’s vote would not be decisive.

A veteran Democratic aide argued that while Reid may be having an increasingly hard time pushing through even relatively mundane items like the extenders package, he has still been effective.

“I think he’s also had an incredibly successful year too,” the aide said. “We’re going to pass financial regulatory reform. We passed health care reform, which no one thought we’d get anytime soon.”

Though most Democrats rejected the notion that Reid’s influence has waned in recent months, Democrats have begun to defect in larger numbers and Republicans are harder to win over.

When the Senate passed the first version of the tax extenders bill — which would have increased the deficit by more than $98 billion — three months ago, Reid lost only one Democrat, moderate Sen. Ben Nelson (Neb.), and he secured the votes of six Republicans.

But on Wednesday that same bill — which, pared back by the House would only increase the deficit by 78.7 billion — lost support from 12 Democrats and received zero GOP votes.

Sen. Olympia Snowe (R-Maine), who voted for the bill in March but against it on Wednesday, said she is very sensitive to adding to the deficit and questions the Democrats’ push for more spending in a tough fiscal environment.

“It’s just that their packages are so big in terms of taxes and spending. That’s the problem, you know,” she said. “It makes it impractical in terms of today’s economic environment.”

And even Democrats acknowledge that the amount of political capital Reid had to expend to pass health care reform, stimulus measures and other controversial items has weakened his lobbying ability.

Sen. Tom Carper (D-Del.) said that comprehensive energy legislation, particularly if it includes controversial cap-and-trade language, could be impossible at this point given the difficult votes many Members have already cast this year.

“For a lot of people looking at the election they may feel … this is a bridge too far,” he said.