The many possible roles of opioids and related peptides in stress-induced analgesia.

The potential role of opioids in analgesic brain mechanisms has consistently been a matter of debate. In the last decade, the debate has shifted from whether there are opioid mechanisms of analgesia to the exact nature of these opioid mechanisms. In this, as in many other cases of biology meeting psychology, the task is made more arduous by the intrinsic and well known difficulties inherent in studying pain on the one hand, and by the newly discovered complexities of opioid biology on the other. We shall discuss the role of opioids in pain regulation in general, and then report on some specific effects of stress on pituitary and brain opioids. In the first section, we shall briefly describe the potential role of two endogenous opioid families in pain modulation. The two families, pro-opiomelanocortin and prodynorphin, produce distinctly different effects on pain responsiveness, may interact with varying opioid and non-opioid receptors in brain, have unique hormonal roles of potential importance to stress and coping, and contain nonopioid peptides also capable of modulating pain. In contrasting them, we hope to reveal to the reader the range of possible roles that these two families may play in pain regulation in general and in stress-induced analgesia in particular. This is not to say that pro-enkephalin products are not relevant to this discussion. We are not considering them here primarily because they are likely to be even more complex in their roles, in view of their widespread anatomy and of the presence of seven distinct opioid cores within their precursor. The second section of the paper will be concerned with the actual effect of stress on @-endorphin and related peptides in pituitary and in brain. In this section, we shall not attempt to prove that b-endorphin is the key to opioid stressinduced analgesia. Rather, we hope to convey to the reader the importance of understanding the cell biology and its regulatory dynamics in attempting to link