Lack of effect of naloxone on pain perception in humans

Abstract

RECENT studies have revealed the existence of endogenous morphine-like compounds in the central nervous system^1–3 and in the pituitary⁴. These compounds, named enkephalin¹ and C-fragment⁴, have been reported to produce analgesia when injected intraventricularly in rats and cats^5,6 and to be antagonised by naloxone which is a potent antagonist of narcotic analgesics. They also have a high affinity for the opiate receptor, which has been discovered in the central nervous system of vertebrates including man⁷, and they can displace naloxone from these receptors^2–4. There is substantial evidence that central grey structures in the midbrain are intimately involved in analgesia. Electrical stimulation⁸ and microinjection of morphine^9,10 in these regions produce analgesia which is antagonised by naloxone. Stimulation of the central grey region in humans¹¹ has been reported to produce marked analgesia which is antagonised by small doses of naloxone¹². In addition, acupuncture analgesia has been reported to be antagonised by naloxone¹³. These findings have led to the hypothesis that there may be an ongoing release within the brain of a morphine-like compound which is partially responsible for pain thresholds. If this were so, then the antagonism of the effects of the endogenous compound by naloxone should affect pain perception. The experiments reported here demonstrate that the perception of experimentally induced pain in normal human subjects is not altered by administration of the opiate antagonist naloxone.