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JAP Volume 7 Issue 1
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editor@japractice.com Sepsis susceptibility
Stop time on chronic pain Researchers have developed a way to delay the rise of neuropathic pain, a chronic form of pain that arises from flawed signals transmitted by damaged nerves, using tiny spheres filled with an anaesthetic derived from a shellfish toxin. The method could potentially allow doctors to stop the
cascade of events by which tissue or nerve injuries evolve into neuropathic pain. The researchers, led by Daniel Kohane, MD, PhD, of Boston Children’s Department of Anaesthesia and Robert Langer, ScD, of MIT, reported the results of animal studies in the Proceedings of the National Academy of Sciences. “Currently neuropathic pain is treated with systemic medications,
Variations in what is called the NFκB gene could play an important role in helping to determine the survival rate of patients who acquire sepsis, the leading cause of death in hospitals. “Wide variability exists regarding the outcome of patients
with severe sepsis, and some of the variability regarding the risk of dying could be caused by genetic variations,” said lead author of the study, published in Anesthesiology, Michael Adamzik, M.D., Associate Professor, Department of Anaesthesiology and Intensive Care Medicine, University Duisberg-Essen, Essen, Germany. “Our study unravels the molecular mechanism by which a common genetic variation in the regulation region of the NFκB gene may amplify and perpetuate inflammation and infection due to sepsis.” Using blood from human subjects, Dr Adamzik and his research
team found that patients with a specific genetic variation (58 percent of the study group) showed, after infection, a two- fold increase of a subunit protein called NFκB-1 and more inflammation compared to patients with other genotypes. The NFκB genetic pathway is believed to be responsible
for amplifying inflammation that takes place in sepsis, and specifically, the protein NFκB-1 could affect the key mechanism of sepsis and possibly influence patient survival rates. “This genetic variation turned out to represent both an
important and independent predictor of mortality in our patients,” said Simon Schäfer, M.D., Research Assistant, Department of Anesthesiology and Intensive Care Medicine, University Duisberg-Essen. “Patients with one genetic variant were associated with an almost two-fold greater risk for death during sepsis. Our study showed for the first time that this genetic variation markedly increases inflammation and influences the risk of dying from sepsis.” Dr Adamzik stated that future studies should work to unravel whether anti-inflammatory sepsis treatment should be adjusted in patients according to genotype. For more information, visit the Anesthesiology website at
www.anesthesiology.org.
but there has been significant interest in using powerful local anaesthetics to block aberrant nerve discharges from the site of injury to prevent the onset of neuropathic pain,” said Kohane. “Others have tried with varying degrees of success to do this in animal models using a variety of methods, but if applied clinically, those methods would require surgical intervention or could be toxic to tissues. We want to avoid both of those concerns.” The team’s method combines saxitoxin, a powerful local
anaesthetic, and dexamethasone, which prolongs saxitoxin’s effects. The two are packaged in liposomes – lipid spheres about 5.5 micrometers wide, or a bit smaller than a red blood cell – for nontoxic delivery to the site of nerve or tissue damage. To assess whether the anaesthetic-loaded liposomes (called
SDLs for saxitoxin dexamethasone liposomes) might work as a potential treatment for neuropathic pain, Kohane and Langer, along with others, attempted to use them to block the development of signs of neuropathy in an animal model of sciatic nerve injury. They found that a single injection of SDLs had a very mild effect, delaying the onset of neuropathic pain by about two days compared to no treatment. Three injections of SDLs at the site of injury over the course of 12 days, however, delayed the onset of pain by about a month. The signal blockade mounted by the SDLs also appeared
to prevent reprogramming of the central nervous system. Astrocytes in the spine, which help maintain the pain signaling in neuropathic patients, showed no signs of pain-related activation five and 60 days after injury in animals treated with SDLs. “Ultimately we’d like to develop a way to reversibly block
nerve signalling for a month with a single injection without causing additional nerve damage,” Kohane explained. “For the moment, we’re trying to refine our methods so that we can get individual injections to last longer and figure out how to generalise the method to other models of neuropathic pain. “We also need to see whether it is safe to block nerve activity in this way for this long,” he continued. “We don’t want to inadvertently trade one problem for another. But we think that this approach could be fruitful for preventing and treating what is really a horrible condition.”
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