Effect of a synthetic enkephalin analogue on spinal nociceptive messages in humans

The effects of a single dose (1.0 mg. i.v.) of a synthetic methionine enkephalin, FK 33-824 (FK) on spinal nociceptive pathways were studied in 3 normal subjects and in 3 paraplegic patients. In normal patients, FK 33-824 produced an increased threshold of a nociceptive flexor reflex of the lower limb as well as a decrease in the slope of the recruitment curve of this reflex as a function of stimulus intensity. The inhibition of a monosynaptic reflex induced by conditioning noxious cutaneous stimulation was also reduced by FK 33-824. In patients, administration of FK 33-824 resulted in marked depression of supraliminal nociceptive reflexes, showing a direct spinal effect of this opioid. In all subjects, FK 33-824 also produced severe side effects. All these effects were naloxone-reversible (0.03 mg/kg. i.v.). The clinical implications of these data are discussed.