ISLAMABAD (AP) — You know a friendship has gone sour when you start making mean jokes about your friend in front of his most bitter nemesis.

So it was a bad sign this week when the U.S. defense secretary joshed in front of an audience of Indians about how Washington kept Pakistan in the dark about the raid that killed al-Qaida leader Osama bin Laden a year ago.

"They didn't know about our operation. That was the whole idea," Leon Panetta said with a chuckle at a Q&A session after a speech in New Delhi, raising laughs from the audience. The Bin Laden raid by U.S. commandos in a Pakistani town infuriated Islamabad because it had no advance notice, and it was seen by Pakistan's powerful military as a humiliation.

The U.S. and Pakistan are starting to look more like enemies than allies, threatening the U.S. fight against Taliban and al-Qaida militants based in the country and efforts to stabilize neighboring Afghanistan before American troops withdraw.

Long plagued by frustration and mistrust, the relationship has plunged to its lowest level since the 9/11 attacks forced the countries into a tight but awkward embrace over a decade ago. The U.S. has lost its patience with Pakistan and taken the gloves off to make its anger clear.

"It has taken on attributes and characteristics now of a near adversarial relationship, even though neither side wants it to be that way," said Maleeha Lodhi, who was serving as Pakistan's ambassador to the U.S. at the time of the Sept. 11, 2001 terror attacks and was key in hurriedly putting together the two countries' alliance.

The latest irritant is Pakistan's refusal to end its six-month blockade of NATO troop supplies meant for Afghanistan. Even if that issue is resolved, however, the relationship may be on an irreversible downward slide. The main source of U.S. anger is Pakistan's unwillingness to go after militants using its territory to launch attacks against American troops in Afghanistan.

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On the Pakistani side, officials are fed up with Washington's constant demands for more without addressing Islamabad's concerns or sufficiently appreciating the country's sacrifice. Pakistan has lost thousands of troops fighting a domestic Taliban insurgency fueled partly by resentment of the alliance with the U.S.

Panetta's comments about the bin Laden raid may have been unscripted, but others he made while in India and Afghanistan seemed calculated to step up pressure on Pakistan. He stressed Washington's strong relationship with India — which Islamabad considers its main, historic enemy — and defended unpopular American drone attacks in Pakistan.

He also said in unusually sharp terms that the U.S. was running out of patience with Islamabad's failure to go after the Pakistan-based Haqqani network, considered the most dangerous militant group fighting in Afghanistan.

Many analysts believe Pakistan is reluctant to target the Haqqanis and other Afghan militants based on its soil because they could be useful allies in Afghanistan after foreign forces withdraw, especially in countering the influence of India.

Pakistan lashed out at Panetta on Saturday and denied the country was providing safe havens for militants.

Panetta "is oversimplifying some of the very complex issues we are dealing with in our efforts against extremism and terrorism," the Foreign Ministry said. "We strongly believe that such statements are misplaced and unhelpful in bringing about peace and stability in the region."

A senior U.S. official described the relationship as "the worst it has ever been."

"This is from Washington's point of view and from Pakistan's point of view, and even among the real well-wishers on both sides who are appalled and befuddled that we can't get past all of this and move beyond," said the official, speaking on condition of anonymity because of the sensitivity of the issue.

After years of frosty relations caused by Pakistan's nuclear weapons program, Washington and Islamabad were thrust together on Sept. 11, 2001, when al-Qaida attacked New York and Washington. The U.S. demanded Pakistan support the war against bin Laden and his Taliban hosts in Afghanistan. The U.S. directed billions of dollars in aid to Pakistan and sought to convince Islamabad it was not simply interested in a "transactional" relationship based on counterterrorism cooperation, but wanted a long-term strategic partnership.

U.S. officials have largely abandoned that argument over the past 18 months as the relationship has suffered repeated crises.

"Because of the toxic atmosphere on both sides, the two countries cannot even work in a transactional way," said Lodhi, the former Pakistani ambassador.

In January 2011, a CIA contractor sparked outrage when he shot to death two Pakistanis in the city of Lahore who he claimed were trying to rob him. Anger over the incident was still simmering when the U.S. killed bin Laden in May.

In November, American airstrikes killed 24 Pakistani troops at two Afghan border posts. The U.S. has said it was an accident, but the Pakistani army claims it was deliberate.

Pakistan retaliated by kicking the U.S. out of a base used by American drones and closing its border to NATO supplies meant for troops in Afghanistan. Negotiations to reopen the route have been hampered by Islamabad's demand for much higher transit fees and Washington's refusal to apologize for the deaths of the Pakistani troops.

The U.S. has attempted to bridge the difference over money by offering to repave highways used by the supply trucks, said a U.S. official, speaking on condition of anonymity because of the sensitivity of the issue.

But Pakistani officials have made clear the route will not reopen without some kind of apology. The U.S. has expressed its regret over the incident but has refused to apologize for fear it could open the Obama administration up to criticism by Republicans upset with Pakistan.

A senior U.S. defense official, Peter Lavoy, arrived in Pakistan on Friday to participate in the negotiations. But Panetta's comments could complicate matters.

Such statements do "water down the willingness to cooperate with the United States," said Imtiaz Gul, director of the Islamabad-based Center for Research and Security Studies.

President Barack Obama showed U.S. anger over the supply issue at a NATO summit last month in Chicago by refusing a one-on-one meeting with Pakistani President Asif Ali Zardari.

However, the U.S. and Pakistan both have reasons to walk the relationship back from the brink.

The U.S. continues to receive some intelligence cooperation from Pakistan on militants and has been able to continue drone strikes in Pakistan's tribal region despite public protests, likely because of tacit agreement by Pakistani military leaders. Both could be threatened if the relationship heads farther south.

Just as important is Pakistan's support on the Afghan war. Pakistan is seen as key to striking a peace deal with the Taliban and their allies in Afghanistan that will allow the U.S. to withdraw most of its combat forces by the end of 2014 without the country descending into further chaos.

Pakistan is keen on freeing up over a billion dollars in frozen U.S. aid, which will only be released if it reopens the supply line. Also, Pakistan can ill afford to become a true enemy of the U.S. at a time when it is struggling to contain its own Taliban insurgency and right its stuttering economy.

But politics on both sides make breaking the impasse difficult, particularly with U.S. elections this fall and Pakistani elections due early next year — possibly even sooner.

Historically, Pakistan's army has steered the relationship with the U.S. But fearing public backlash in a country where anti-American sentiment is rampant, the generals have tossed the NATO supply line issue to Pakistan's weak and unpopular civilian government. The politicians are reluctant to do anything that could hurt their election prospects.

"The longer Islamabad delays and dithers, the opinion in Washington is hardening," said Lodhi. "Time is the enemy of a reset in relations."

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AP Special Regional Correspondent for Afghanistan and Pakistan Kathy Gannon contributed to this report.