Last week England suffered a major setback when Andrew Flintoff, who missed the drawn series opener at Lord's, was ruled out for the rest of the season with an ankle injury.
England had hoped the star all-rounder would return to captain them for the second match of the series at his Lancashire home ground on Thursday. Instead he faces a fresh operation.
And their pace bowling resources were further depleted Tuesday when Durham quick Liam Plunkett was ruled out of this match, and the third Test at Headingley, with a side strain.
Already without Ashes-winning captain Michael Vaughan (knee), fast bowler Simon Jones (knee) and spinner Ashley Giles (hip), England at least have the consolation of being at home where replacements from the county game are plentiful in number, if not quality.
Pakistan though have been equally hard-hit. They remain without the pace trio who were all absent at Lord's: Shoaib Akhtar (ankle), Mohammad Asif (elbow) and Rana Naved-ul-Hasan, who has been ruled out of the whole series with a groin problem.
Batsmen Younis Khan (knee) and Shoaib Malik (elbow) are, however, available for selection once again.
But there was futher bad news for Pakistan on Tuesday when leg-spinning all-rounder Shahid Afridi was hit on his right arm when batting in the nets and seamer Rao Iftikhar Anjum, summoned as a replacement, had to return home for a family bereavement.
The loss of Flintoff, however, will be keenly felt by his adoring Manchester crowd, but Pakistan coach Bob Woolmer said: "We can't look at individuals.
"We must look at the England team as it comes and get on with the game of cricket. We'll just carry on with the game."
As for Plunkett's injury, the ex-England batsman added: "Whether it reduces England's capacity to bowl us out remains to be seen. They have other bowlers - and as Kevin Pietersen has been pointing out, it gives other people the opportunity to show what they can do."
Sajid Mahmood, who could return to Test cricket on his Lancashire home ground, and Gloucestershire's Jon Lewis are the pace bowlers now vying for a spot in Flintoff's absence.
Left-arm spinner Monty Panesar bowled with guile and economy at Lord's without ever threatening to run through Pakistan on the final day.
England have uncapped off-spinner Jamie Dalrymple, one of the few success stories from their 5-0 one-day series thrashing by Sri Lanka, in what is now a 13-man squad and they could be tempted to give a debut to the Middlesex man on account of his supposedly superior batting to that of Panesar.
But whether Dalrymple is any more likely to dismiss Pakistan captain Inzamam-ul-Haq, who has now made nine consecutive Test fifties against England, or Mohammad Yousuf, whose double century at Lord's was his second in as many Tests against England, remains an open question.
Pakistan have slow bowling issues of their own with a decision on whether to recall leg-spinner Mushtaq Ahmed, currently playing for English county Sussex, still to be taken.
But although this week marks the 50th anniversary of England off-spin great Jim Laker's 19 for 90 against Australia at Old Trafford - the best individual match return in Test history - Woolmer said spin was no longer such a factor at the Manchester venue.
And, in any event, he was confident Afridi would be fit to take his place alongside fellow leg-spinner Danish Kaneria in the tourists' attack.
"We've looked at the pitch hard; we've seen the records over the last few years on the pitch, and the spinners haven't been that successful here," said Woolmer.
As for Afridi, he added: "He can move the arm - it's not broken.
"It was a little bit tender to start with. But touch wood he'll be available to play and he'll be 100 percent. He's a tough man from the north, a Pathan."
But he was more cautious about Akhtar's prospects for the series.
"Shoaib is reacting well to the first few days back bowling," Woolmer said. He wants to play in this Test. But we know better, so we won't rush him."