• Mechanism of Action of Key Regulatory Protein Confirmed in New Research
    Results from new research conducted at the La Jolla Institute for Allergy & Immunology (LJI) have identified the mechanism by which the protein Sharpin contributes to the regulation of immunosuppressive T cells or Tregs that are essential to the prevention of autoimmune disorders. Previous studies have identified that Sharpin-deficient mice develop inappropriate inflammation, but the new research uncovers that this is due to the absence of a previously unknown cell survival mechanism orchestrated by Sharpin that ensures sufficient Treg populations. This new understanding may illuminate new approaches to the control of immune responses in the treatment of inflammation, autoimmune disorders, or cancer. In the study, the research team observed an insufficiency of Tregs in the tissue of Sharpin-deficient mice, who developed skin lesions and organ inflammation shortly after birth. The researchers then performed a “rescue” experiment by transferring Tregs from normal mice (mice with intact Sharpin) into mutant mice and observed that the manipulation reduced severity of the inflammation. Study coauthor Hyung-seung Jin, PhD, commented: “Treg-based intervention has in fact been proposed as a novel therapeutic means to treat various inflammatory diseases, meaning that knowing how Treg function is regulated could speed development of effective treatments.” To access the library of information about inflammation, click here. The findings are published in the February 1 issue of Nature Immunology. Read more about the findings here. The article abstract may be read here.  
  • Study of Veterans Suggests Risk of Accidental Death Varies with Dosage Level
    A recently published study concludes that the risk of accidental overdose from prescription opioids is closely tied to the dosage level prescribed, and that the threshold for safe prescribing may be lower than most current guidelines specify. The findings are based on a close examination of the medical and prescription records of some 450 veterans with chronic pain, half of whom died from accidental opioid overdose, and half who did not overdose. On average, the cohort who overdosed had been prescribed a dosage that was 71% higher than those who did not. The study was led by Amy Bohnert, MHS, PhD, an epidemiologist with the University of Michigan Medical School and VA Ann Arbor Healthcare System, and appears online in the journal Medical Care. Current guidelines for opioid prescribing recommend a maximum daily dose of 100 morphine-equivalent milligrams (MEM); however, the study found that the average prescribed dose in the overdose cohort was 98 MEM versus 48 MEM among those who did not. Dr. Bohnert was a member of the Core Expert Group created by the CDC to develop new prescribing guidelines for opioids. “Our findings suggest that changing clinical practices to avoid escalating doses for patients with chronic pain could make a major difference in the number of patients who die,” she commented. Draft guidelines released by the Core Group recommend that providers consider other painkillers first, prescribe the lowest effective dosage, put additional precautions in place for any patient to whom they prescribe more than 50 MEM a day, and avoid prescriptions over 90 MEM a day for chronic pain patients. Read more about the study findings here. The article abstract may be read here.
  • Central Nervous System and Diabetic Nerve Disease
    In a study in the journal Pain provides evidence that painful diabetic peripheral neuropathy (DPN) is caused in part by the central nervous system (CNS). Dr. Solomon Tesfaye, Sheffield (UK) Teaching Hospitals NHS Foundation Trust in the United Kingdom states, "Although DPN has been considered a disease of the peripheral nerve, from numerous studies it is becoming apparent that there are indeed changes within the CNS that...appear to be concomitant with the evolution of painful and painless DPN." Advanced imaging is providing new insights into DPN, which occurs in half of diabetics. Although studies have highlighted the dying back of nerve cells and the loss of nerve cell insulation, new evidence shows that small blood vessel disease leads to hypoxia of the peripheral nerves and contributes to DPN. Further studies are needed. To access the library of information on diabetic peripheral neuropathy, click here. To read the article, click here. Access the journal abstract, here.
  • Endomorphin May Provide Benefits Without Side Effects
    A new drug engineered by scientists at Tulane University is a version of naturally occurring endomorphin. It targets the same pain-relieving opioid receptor as morphine. Rats were treated with endomorphin or morphine. Pain relief with endomorphin was greater than or equal to pain relief with morphine, but without the side effects of impaired motor skills and respiratory depression. In addition, treatment with endomorphin did not induce addictive behavior. According to lead researcher James Zadina, "It's unprecedented for a peptide to deliver such powerful pain relief with so few side effects." Zadina is professor of medicine, pharmacology and neuroscience at Tulane University School of Medicine. Clinical trials on humans should start within 2 years. To access the library of information about morphine, click here. To read the article, click here.
Daniel Carr, MD, FABPM
Pain Research, Education, and Policy Program
Department of Public Health and Community Medicine
Tufts Medical Center
Boston, MA


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