Comparison of the effects of ventral medullary lesions on systemic and microinjection morphine analgesia

Abstract

The effects of electrolytic lesions of the nucleus raphe magnus (NRM), nucleus reticularis paragigantocellularis (PGC) and nucleus raphe alatus (NRA) on analgesia elicited in the rat from systemic morphine and morphine microinjection into the periaqueductal gray (PAG) were evaluated using the tail flick test. No consistent change in baseline pain sensitivity was observed following lesions of the NRM, PGC or NRA. To determine the effect of ventral medullary lesions on systemic porphine analgesia, pain sensitivity was assessed prior to and 40 min after 6 mg/kg morphine administration (i.p.) at 2 days preceding lesioning and 5, 12 and 19 days post-lesion. NRM and PGC lesions produced only slight reductions in analgesia at 5 days after surgery. It was observed that large NRM, large PGC, and NRA lesions significantly attenuated analgesia evaluated at 12 days post-lesion. Smaller lesions confined within the NRM or PGC were reliably less effective than the larger lesions in reducing analgesia. In a subsequent study, 5 μg morphine in 0.5 μl saline was microinjected into the ventral PAG at the level of the dorsal raphe. Identical testing procedures were used and the analgesia was assessed at 2 days before lesioning and 5 and 12 days post-lesion. In contrast to the previous study, large NRM lesions abolished analgesia as early as 5 days following lesioning. Small NRM lesions were less effective and PGC lesions were generally ineffective in attenuating analgesia induced by morphine microinjection. We conclude that the NRA may act as a functional unit in the mediation of systemic morphine analgesia. In contrast, analgesia elicited from intracerebral (PAG) morphine microinjection is mediated via the NRM.