Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of selective delta and mu opioid antagonists has provided evidence that delta opioid receptors within the brain mediate the endogenous opioid component of endotoxic shock hypotension. The selectivity of these delta and mu antagonists was demonstrated by their differing effects upon morphine analgesia and endotoxic hypotension. The mu antagonist beta-funaltrexamine, at doses that antagonized morphine analgesia, failed to alter shock, whereas the delta antagonist M 154,129: [N,N-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH] (ICI) reversed shock at doses that failed to block morphine analgesia. Therefore, selective delta antagonists may have therapeutic value in reversing circulatory shock without altering the analgesic actions of endogenous or exogenous opioids. Additional data revealed that prior occupancy of mu binding sites by irreversible opioid antagonists may allosterically attenuate the actions of antagonists with selectivity for delta binding sites. For endogenous opioid systems, this observation provides an opportunity to link in vivo physiological responses with receptor-level biochemical interactions.
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PMID:Multiple opioid receptors in endotoxic shock: evidence for delta involvement and mu-delta interactions in vivo. 632 51

Gram-negative sepsis and subsequent endotoxic shock remain major health problems in the United States. The present study examined the role of morphine in inducing sepsis. Mice administered morphine by the subcutaneous implantation of a slow-release pellet developed colonization of the liver, spleen, and peritoneal cavity with gram-negative and other enteric bacteria. In addition, the mice became hypersusceptible to sublethal endotoxin challenge. The effects were blocked by the simultaneous implantation of a pellet containing the opioid antagonist naltrexone. These findings show that morphine pellet implantation in mice results in the escape of gram-negative organisms from the gastrointestinal tract, leading to the hypothesis that morphine used postoperatively or chronically for analgesia may serve as a cofactor in the precipitation of sepsis and shock. In addition, morphine-induced sepsis may provide a physiologically relevant model of gram-negative sepsis and endotoxic shock.
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PMID:Morphine induces sepsis in mice. 920 65

Besides providing effective analgesia, thoracic epidural anesthesia (TEA) has been shown to decrease perioperative morbidity and mortality. Because of its vasodilatory properties in association with the sympathetic blockade, however, TEA may potentially aggravate cardiovascular dysfunctions resulting from sepsis and systemic inflammatory response syndrome. The objective of the present study was to assess the effects of TEA on hemodynamics, global oxygen transport, and renal function in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 18), Salmonella typhosa endotoxin was centrally infused at incremental doses to induce and maintain a hypotensive-hypodynamic circulation using an established protocol. The animals were then randomly assigned to one of two groups. In the treatment group, continuous TEA was initiated with 0.1 mL.kg of 0.125% bupivacaine at the onset of endotoxemia and maintained with 0.1 mL.kg.h. In the control group, the same amount of isotonic sodium chloride solution was injected through the epidural catheter. In the animals surviving the entire experiment (n = 7 per group), cardiac index and mean arterial pressure decreased in a dose-dependent manner during endotoxin infusion. In the TEA group, neither systemic hemodynamics nor global oxygen transport were impaired beyond the changes caused by endotoxemia itself. Urinary output was increased in the TEA group as compared with the control group (P < 0.05). In this model of endotoxic shock, TEA improved renal perfusion without affecting cardiopulmonary hemodynamics and global oxygen transport.
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PMID:Effects of thoracic epidural anesthesia on hemodynamics and global oxygen transport in ovine endotoxemia. 1711 38