The opioid/anti-opioid balance in shock: a new target for therapy in resuscitation

Teleologically, pain is of paramount importance for survival and induces the organism to cope in an active way with aggressions from a basically hostile environment. While the activation of endogenous analgesic (opioid) systems typically occurs in conditions of surrender (pre-terminal conditions, sustained tortures, etc.), the activation of endogenous anti-analgesic systems triggers mechanisms of active or passive defence (such as camouflage) aimed at survival. The distinctive features of the main anti-analgesic systems (melanocortinergic, cholecystokininergic, thyroliberinergic) and the dramatic results obtained in experimental pre-terminal conditions (hemorrhagic shock, prolonged respiratory arrest) with the administration of their neuropeptide transmitters (ACTH and several ACTH-fragments, including alpha-MSH, CCK peptides and thyrotropin-releasing hormone) are here reviewed. The study of the mechanisms underlying the resuscitating effects of these neuropeptides has led to the discovery of the (often extremely potent) resuscitating effect of other drugs (protoveratrines, nicotine, centrally-acting cholinergic agents, ganglion-stimulating drugs). It is particularly remarkable that in pre-terminal conditions these neuropeptides and drugs have highly impressive effects on cardiocirculatory parameters at doses that are almost or actually inactive under normal conditions, and that their resuscitating effect is obtained without the need for any other supportive treatment and at dose-levels well below toxic ranges. Finally, in hemorrhage-shocked animals, the treatment with anti-analgesic neuropeptides shortly after bleeding considerably extends the time-limit for an effective and definitively curing blood reinfusion. This would be of self-evident importance in clinical practice, because an extremely simple, non-toxic first-aid treatment in the field, shortly after a massive hemorrhage, could resuscitate the patient for a period sufficient to effectively set up the most appropriate in-hospital treatment.