Endogenous Opioids and Opioid Antagonists in Endotoxic and Septic Shock: A Current Perspective

Abstract

For several years after their discovery in 1975, the endogenous opioids (or “endorphins”) were at the forefront of investigations characterizing the role of peptides in biology and medicine. In 1978, it was first proposed that endogenous opioid systems were involved in endotoxic shock [1] and other forms of critical illnesses. In retrospect, the postulation was simple: that the “morphine-like” substances within the body could be released in excessive amounts by the severe physiological stress of shock and trauma; this “overdose” of endogenous opioids would contribute to the decreased cardiovascular function and organ perfusion that characterize shock [2]. The availability of naloxone (Narcan), a competitive antagonist that selectively blocks or reverses the actions of morphine or endogenous opioids, provided an opportunity to test this hypothesis. The first several preclinical and clinical publications clearly demonstrated that naloxone, administered following the onset of shock, improved arterial pressure and other hemodynamic endpoints and, in some studies, survival. By inference, evidence indicated that the body’s own opiate “painkillers” were indeed involved in the pathogenesis of endotoxic or septic shock.