D-Ala2]-methionine enkephalinamide (DALA): characterization of antinociceptive, cardiovascular, and autonomic nervous system actions in conscious and pentobarbital-anesthetized rats

The antinociceptive, cardiovascular, and autonomic nervous system actions of [D-Ala2]-methionine enkephalinamide (DALA) were assessed in conscious and pentobarbital-anesthetized rats. Intravenous administration of DALA inhibited the tail-flick reflex evoked by noxious radiant heat in both conscious and pentobarbital-anesthetized rats. In general, the magnitude of the inhibition was not significantly affected by the presence of pentobarbital-anesthesia. DALA also induced hypotension and bradycardia in these rats, but these responses were significantly attenuated by pentobarbital-anesthesia. Arterial blood flows were initially decreased and vascular resistances increased in mesenteric, renal, and hindquarter beds following DALA administration, but these parameters rapidly returned to baseline levels except in the hindquarter bed where flows increased significantly above baseline levels. All of the changes in blood flows were significantly greater in conscious compared to pentobarbital-anesthetized rats. In intact pentobarbital-anesthetized rats, DALA induced inhibition of renal sympathetic nerve activity. However, DALA induced a pressor response with a brief increase in renal sympathetic nerve activity in rats with bilateral vagotomy. Similarly, in the conscious rat with ganglionic blockade, DALA induces a brief pressor response. These outcomes indicate that the brief hypotension observed in the intact rat following administration of DALA is probably the net outcome of a large vagally-induced decrease in sympathetic tone and a small increase in sympathetic tone of either neurogenic or peripheral origin. These outcomes are discussed in terms of cardiovascular-somatosensory interactions.