Opiate antagonists in traumatic shock

Abstract

In experimental animal studies, opiate receptor antagonists (such as naloxone) and physiological opiate antagonists (thyrotropin-releasing hormone [TRH] have been used with some success to improve outcome and physiological variables following traumatic shock associated with hypovolemia, spinal cord trauma, and head injury. Naloxone at high doses (in the mg/kg range) improves blood pressure and survival following hypovolemic shock in some species subjected to fixed-pressure shock. Similarly, naloxone treatment in the same dose range improves blood pressure and outcome following traumatic spinal shock as well as shock associated with traumatic head injury in selected animal models. The high doses of naloxone required in these studies suggest that the beneficial effects may be due to actions at relatively naloxone-insensitive opiate receptors, such as the kappa-receptor. Changes in the putative kappa-receptor ligand dynorphin are found after hypovolemic shock and traumatic injury to the brain or spinal cord. Opiate receptor antagonists with increased selectivity for the kappa-receptor may be superior to naloxone in the treatment of these conditions. TRH or TRH analogs similarly improve blood pressure and outcome following hypovolemic or spinal shock. Clinical trials of naloxone (at high doses) in human spinal cord injury have begun, and there are plans for clinical trials of naloxone in human head trauma and of TRH in human spinal cord injury.