Nuclei within the rostral ventromedial medulla mediating morphine antinociception from the periaqueductal gray

The relative contributions of nuclei within the rostral ventromedial medulla (RVM) involved in mediating morphine induced antinociception from the periaqueductal gray (PAG) were examined. Lidocaine injections (4%) at the time of morphine's maximal response were used to provide a localized neural block and were administered in the nucleus raphe magnus/reticularis gigantocellularis pars alpha (RMg/GiA; commonly referred to as RMg), reticularis gigantocellularis (Gi) and reticularis paragigantocellularis lateralis (LPGi). Microinjection of morphine (6 nmol; 0.5 microliter) into the PAG of awake rats produced an inhibition of the tail-flick reflex that was maximal after 30 min. This response was unaffected by a single medial lidocaine injection (0.5 microliter) into the RMg/GiA or Gi, bilateral injections into the Gi or LPGi or triple injections that included both the RMg/GiA and LPGi. A partial, non-significant block of morphine's response was observed either by bilateral injections (0.5 microliter) into both the Gi and LPGi (% inhibition = 16.4 +/- 24.8) or by bilateral injections in the LPGi and a single medial injection into the Gi (% inhibition = 41.5 +/- 29.8). However, injection of a greater volume of lidocaine (1 microliter) into the RMg/GiA or bilaterally into the LPGi affected adjacent medial and lateral tissue, and completely inhibited morphine's response. Furthermore, triple injections of lidocaine (0.5 microliter) into the Gi or bilateral injections (0.5 microliter) into the Gi and a single medial injection into the RMg/GiA completely blocked morphine's antinociceptive response. These results indicate that morphine antinociception from the PAG is mediated by a large volume of tissue in the RVM containing nuclei located both medially and laterally. Additionally, the principal nuclei involved in this response appear to be the Gi and RMg/GiA.