Initially aspirin can help extreme pain (4)
I believe the answer is:
ache
'pain' is the definition.
(ache is a kind of pain)
'initially aspirin can help extreme' is the wordplay.
'initially' says to take the initial letters.
The initial letters of 'aspirin can help extreme' is 'ACHE'.
(Other definitions for ache that I've seen before include "Twinge" , "burn" , "Play up" , "Suffer dull pain" , "Persistent dull pain" .)