Operation, anesthesia, and the endorphin system

Endogenous opioid peptides regulate a multitude of neuronal pathways and extraneural targets (e.g., white blood cells). Acting in the periphery and at central sites of afferent integration within multiple compartments at multiple levels, they modify the secretion of other hormones yet are themselves secreted during stress to produce important biological effects. Usually quiescent, the opioid system becomes active during a host of stresses to optimize, integrate, and buffer bodily responses. During stress, endorphins act to limit sympathetically driven responses such as tachycardia and vasoconstriction; however, if given to resting subjects, opiates may evoke the very responses they inhibit during stress. As the roles of individual opioid peptides and opiate receptors are studied in increasing depth, an amazing degree of functional heterogeneity and detail has emerged. Such knowledge has barely begun to be exploited in creating the next generation of therapeutics.