Opiate and opioid peptide effects on brain stem neurons: relevance to nociception and antinociceptive mechanisms.

That the brain stem, particularly the reticular core, is involved in the receipt and processing of sensory information of wide variety, including pain, is well appreciated [e.g., 26,104,105,230]. While nociception and ~tinociception have long been poorly understood, the recent past has seen significant advances made in our appreciation and understanding of the involvement of brain stem areas in nociception [e.g., 33,38,55,125] and antinociceptive mechanisms [ 157159,262,265]. The demonstration of stereospecific, saturable and reversible sites in the central nervous system which bind opiates (opiate receptors [200,233,240]) and the discovery of endogenous ligands for this receptor (endorphins and enkephalins [ 110,232]), both of which are present in brain stem areas relevant to this essay [9,10,197,217,244], have led, in concert with information reviewed by those cited above, to postulation of descending antinociceptive systems and endogenous mechanisms of antinociception localized in the brain stem. Basbaum and Fields [ 15,16,80,81] have reviewed anatomic and physiolo~c~ evidence and suggest a role for the medullary reticular formation in the modulation of pain. The participation of the medullary reticular formation in the modulation of pain as currently proposed requires the activation of neurons in certain brain stem areas, However, recent reviews of the electrophysiological effects of opiates [44,111,183] conclude that their pharmacologically important action in the brain stem is depression of neuronal activity. In their general pharmacology, opiates are indeed powerful depressants of many systems. In addition, recent evidence suggests that enkephalinergic interneurons throughout the brain exert a predominant inhibitory effect (34,60,115,1 l&150,176]. Thus, that opiates and opioid peptides are apparently suppressive to neuronal activity is not consonant with the notion that their involvement in antinociception relates to an activation of selected neurons in the brain stem.