Multiple Morphine and Enkephalin Receptors and the Relief of Pain

AFTER thousands of years, opiates remain the drugs of choice for severe pain. Their potency and ability to relieve the "hurt" associated with nociceptive stimuli without significantly altering such basic sensations as touch, temperature, and proprioception separate them from all other analgesics. Despite these advantages, side effects such as tolerance, physical dependence, respiratory depression, and constipation greatly limit their usefulness. In addition to these physiological actions of the opiates, their abuse is also a concern, but this remains uncommon in the treatment of acute pain and cancer pain. Opiates mimic the actions of a series of brain peptides and activate endogenous pain-modulating systems by binding to a number of different types of opioid receptors, each mediating distinct actions. Recent work indicates that the receptors responsible for many opiate side effects differ from those producing analgesia, implying that analgesics lacking these unwanted actions may be possible. This article reviews some physiological