In "Ren's Toothache", the fly's complaints about Ren airing out his gum holes was based on the reaction of the customer at a restaurant who overheard John Kricfalusi discussing gross-out gags with a co-worker.
Originally, an episode named "Mans best friend" was supposed to air as the second segment of this episode after "Rens toothache" but was pulled from Nickelodeon so therefore they replaced it with an edited version of the pilot. It was pulled for tobacco references and for violence. It remained unaired until 2003 when it aired on Spike TV as the unofficial pilot for "Ren and Stimpy adult party cartoon" and even went with a TV-MA rating.
In big house blues everything from the intro to the theme is taken from this episode