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$_="FourThreeTwoOne, Three, Four, One, Two";
$1="Three";
$second="&&&&";
s/$2/$second/g;
print;

$1="Three";

s/$2/$second/g;

{
    local $_="FourThreeTwoOne, Three, Four, One, Two";
    # ...
}

use strict;
use warnings;

my $second="&&&&";