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A high-ranking spokeswoman for former Pakistan prime minister Imran Khan quit their party on Tuesday after days of repeated arrests and release that followed deadly protests over Khan's detention.
Khan was detained two weeks ago on graft charges, sparking days of street violence, before the Supreme Court declared his arrest illegal and freed him.
Pakistan Tehreek-e-Insaf (PTI) senior vice-president Shireen Mazari said she had been subjected to "12 days of arrest, release, abduction and release".
"I have decided that I am leaving active politics. From today onwards I am not a part of PTI or any political party," she told reporters.
"All I can say is that I am not feeling well," she said, appearing dejected in a brief news conference where she cited health and family issues for her resignation.
Mazari was among the most vocal critics of the military-backed establishment and its role in the downfall of Khan, who was ousted in a parliamentary no-confidence vote in April last year.
PTI said Mazari had been arrested and released five times since the protests, including on charges of inciting the protest violence.
More than a dozen senior party leaders have also been arrested, with at least eight still in detention.
Analyst Hasan Askari predicted more resignations in the coming days.
"It is a part of the process of isolating Imran Khan and telling him that one can't be an effective political player in Pakistani politics if one fights with the establishment," he told AFP.
Since he was ousted from office, 70-year-old Khan has waged an unprecedented campaign of defiance against the military establishment.
He accuses the top brass of orchestrating his downfall and even plotting a November assassination attempt in which he was shot in the leg, allegations that the army denies.
His arrest at the Islamabad High Court came just hours after he repeated the claim and was seen by his party as a bid to quash support ahead of elections due no later than October.
People rampaged through cities, setting fire to buildings, blocking roads and clashing with police outside military installations during unrest in which nine people were killed.
The military has denied claims by Khan that "agencies" planned the violence to smear his party.
Islamabad has pledged to try in military courts those accused of violence against army installations during riots.
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