In case of direct conflict between the nuclear powers, whichever one finds themselves on the cusp of defeat will probably use nukes. (This assumes an actual shooting war between them directly, not a proxy war.)
Iran IS that crazy. And a new government in Pakistan could become that crazy. (Remember, the Pakis - at least some of them - were hiding Osama.)
Israel won't accept defeat and being overrun by anyone (which would mean their actual destruction and genocide) without going nuclear.