It's most hurtful - therefore take a break (6)
I believe the answer is:
sorest
'it's most hurtful' is the definition.
I can't tell whether this definition defines the answer.
'therefore take a break' is the wordplay.
'therefore' becomes 'so' ('so' can mean 'consequently' or 'therefore').
'take a break' becomes 'rest' (to have a rest is to take a break).
'so'+'rest'='SOREST'
Can you help me to learn more?
(Other definitions for sorest that I've seen before include "Stores in most painful way" , "In greatest discomfort" , "Most aggrieved" , "Most wounded" , "Most tender" .)