Endogenous opioids in the CNS

This short and concise paper was the first to unequivocally reveal that there were endogenous opioids in the central nervous system (CNS), identify their peptide nature and sequence, and show that they exerted physiological inhibitory effects. The idea that there were natural opioids fitted with concurrent reports of opiate-binding sites, and this led to the description of multiple receptors with their own families of peptide transmitters. No truly novel opioid drugs have emerged since, and attempts to protect and manipulate the enkephalins for pain control have yet to be successful. This does not detract from this key study, which made us think about pain modulation in a different way, and subsequent work has clearly shown how endogenous opioid signalling is critical in CNS function, perhaps most importantly in endogenous pain control, such as that harnessed by placebo analgesia.

A review of perioperative anesthesia and analgesia for infants: updates and trends to watch

This review focuses on pharmacokinetics and pharmacodynamics of opioid and non-opioid analgesics in neonates and infants. The unique physiology of this population differs from that of adults and impacts drug handling. Morphine and remifentanil are described as examples of older versus recently developed opiates to compare and contrast pharmacokinetics and pharmacodynamics in infants. Exploration of genetics affecting both pharmacokinetics and pharmacodynamics of opiates is an area of active research, as is the investigation of a new class of mu-opiate-binding agents which seem selective for analgesic pathways while having less activity in pathways linked to side effects. The kinetics of acetaminophen and of ketorolac as examples of parenteral non-steroidal analgesics in infants are also discussed. The growth in regional anesthesia for peri-operative analgesia in infants can fill an important role minimizing intra-operative anesthetic exposure to opioids and transitioning to post-operative care. Use of multi-modal techniques is recommended to decrease undesirable opiate-related side effects in this vulnerable population.