This is a review of research aimed at elucidating how various opiate analgesia substrates in rat brain stem interact with one another to bring about opiate analgesia. The three substrates studied are the midbrain periaqueductal grey (PAG), the bulbar nucleus raphe magnus (RM), and the bulbar nucleus reticularis paragigantocellularis (PGC). The methods used in the reviewed studies are unique in that behavioral and neuronal responses are assessed in consequence of nanoinjecting opiates (met-enkephalin) into subset pairs of these structures. Responses to single and conjoint injections are compared. Effects on neuronal and behavioral responses in consequence of disruption of these structures with tetracaine block are also discussed. It is seen that PGC cannot serve as an opiate analgesia substrate if the functional integrity PAG is impaired. However PAG does not depend on PGC's functional integrity.