Neuropeptides in shock and traumatic injury: sites and mechanisms of action

∂-Opioid Receptors and the Secretion of Growth Hormone in Man: Effect of Opioid ∂-Receptor Agonist Deltorphin on GH Responses to GH-Releasing Hormone and Insulin-Induced Hypoglycemia

“…31-33]. Evidence is available from animal models of endotoxic shock that ¿-opioid re ceptors at or near the nucleus tractus solitarius may in fluence the sympathetic function [34]. This seems to favor the assumption of a possible influence of DT on the sym pathetic outflow, although our data do not provide any direct proof for this view.…”

Effects of TRH in Circulatory Shock and Central Nervous System Ischemia

“…Early experiments established that the opioid antagonist naloxone either blocked or rapidly reversed both phases of hypotension in ratsL9 and other species. (For a review, see references [11][12][13][14]. As an alternative therapeutic strategy to opiate receptor antagonists, we investigated the effects of TRH in the rat endotoxic shock model.20,21 TRH was shown to exert a pressor effect that was mediated in part by CNS actions (increased sympathomedullary outflow) as well as by direct peripheral effects (see be lo^).^^****^^ In mild-endotoxemia, TRH improved arterial pressure and survival.21 However, in severe endotoxic shock, although arterial pressure was improved, survival apparently was diminished by TRH injections.22 Perhaps because of the early hyperactivation of compensatory mechanisms by TRH during endotoxic shock (including increased catecholamine and glucose release), fewer physiological resources are available during the later stages of shock to maintain vital functions.…”

“…Over the past decade, extensive evidence has accrued to indicate that endogenous opioid systems contribute to the pathophysiology of circulatory shock, CNS injury, and CNS ischemia. [8][9][10][11][12][13][14][15][16] Much of this evidence relies on the established therapeutic effects of opioid antagonists (e.g., naloxone) in clinically relevant experimental models of these disorders. We were concerned, however, that the clinical use of opioid antagonists, such as naloxone, to treat circulatory shock, traumatic injuries, or CNS ischemia would potentially enhance pain by blocking endogenous opioid analgesia andor preventing the use of morphine for pain relief.…”

Opioid Peptides and Their Antagonists: A Role in Respiratory Function

“…10 Since the endogenous opioid system is nor mally quiescent, the use of physiologic or behav ioral stressors to activate the endogenous opioid system has been used in combination with the opioid antagonist naloxone (Narcan) in order to define the various biologic actions of endogenous opioids. 12 Studies with naloxone have provided information leading to the characterization of a pathologic role for endogenous opioid systems in septic, hemor rhagic, neurogenic, and anaphylactic shock, as well as spinal cord injury, 13 thus providing clues to the etiology of these syndromes. Similar to the known involvement of endogenous opioids in cardiovas cular function, 14 an important role for the opioid peptides in respiratory function is emerging.…”

“…50,51 Indeed TRH has been shown to have therapeutic value in reversing different forms of experimental circulatory shock and spinal cord injury in laboratory animals. 13,14 Further more, clinically TRH has been demonstrated to limit the neuromuscular deficits after spinal cord trauma 52 and to improve motor function in amy otrophic lateral sclerosis. 53 Together, these phar macologic effects of TRH suggest many novel and important therapeutic uses for this tripeptide in patient care.…”