Narcotic analgetics: CNS sites and mechanisms of action as revealed by intracerebral injection techniques

Abstract

The known regions within the CNS where the local application of narcotic agonists can elicit a behaviorally defined elevation of the nociceptive threshold were identified. The pharmacological, anatomical and behavioral characteristics of these drug/side effect entities were discussed. Other sites where injections of narcotics evoked not analgesia, but some presumed correlate of analgesia, were similarly identified and discussed. Where sufficient data were available plausible constructs were created to explain how narcotics might produce an analgetic effect by an action limited to specific loci. Although the proposed mechanisms are complex, all of the constructs suggest that the analgetic effect of locally applied narcotics may be a consequence of either a direct passive blockade of nociceptive through-put (spinal cord, lateral mesencephalic reticular formation, n. [nucleus] reticulo gigantocellularis) and/or a direct or indirect (via efferent projections from the structure injected to other structures) recruitment of active inhibition of nociceptive throughput (mesencephalic central gray). Considerable emphasis is placed upon the latter process. Even in the spinal cord, some of morphine''s actions on sensory transmission may be mediated by an active process originating in cells within the substantia gelatinosa. The phenomenon of analgesia produced by the systemic administration of a narcotic depended upon both passive and active processes and narcotic action in both spinal and supraspinal structures contributes to the manifestations of this behaviorally defined phenomenon.