Nettle rash itchy, less excruciating first of all (4)
I believe the answer is:
rile
'nettle' is the definition.
(I know that nettle can be written as rile)
'rash itchy less excruciating first of all' is the wordplay.
'first of all' says to take the initial letters.
The first letters of 'rash itchy less excruciating' is 'RILE'.
(Other definitions for rile that I've seen before include "Informally, annoy or irritate" , "Make angry" , "Exasperate" , "Provoke" , "Bother" .)