Syndicate content

Archive - Apr 16, 2015

POSSIBLE NEW APPROACH TO RELIEF FROM CHRONIC PAIN: Drugs Targeting A3 Adenosine Receptor Restore GABA Signaling and Turn Off Pain Signals in Spine; Lead Molecules for Potential Clinical Trials Have Been Identified

In a study published in the April 15, 2015 issue of the Journal of Neuroscience, Saint Louis University (SLU) scientists, led by Professor of Pharmacological and Physiological Sciences Daniela Salvemini, Ph.D., discovered that drugs targeting the A3 adenosine receptor can "turn off" pain signals in the spinal cord to provide relief from chronic pain. The article is titled “Engagement of the GABA to KCC2 Signaling Pathway Contributes to the Analgesic Effects of A3AR Agonists in Neuropathic Pain.” Pain is the most common reason that people seek medical attention, but the available treatments--most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and opioids--are not always successful at relieving pain in patients with chronic pain. For this reason, Dr. Salvemini and colleagues teamed up with researchers from the NIH, the University of Arizona, and two institutes in Quebec, Canada, to investigate a new target for treating chronic pain: the A3 adenosine receptor (A3AR). In earlier studies, Dr. Salvemini's laboratory demonstrated that two drugs that target the A3AR--IB-MECA and MRS5698--were effective in treating several models of chronic pain, including painful chemotherapy-induced neuropathy, metastatic cancer pain, and nerve injury. More recently, the group sought to uncover the mechanism of A3AR pain relief. "Chronic pain can result from the loss of regulatory mechanisms in the nervous system pathway that transmits pain," Dr. Salvemini said. "Adenosine acts as a regulatory signaling molecule in other areas of the nervous system, so we hypothesized that A3AR might also play a role in regulating pain signals during pain processing." Indeed, Dr.

Fatty Acids in Fish Oil Found Crucial to Brain Development

While recent reports question whether fish oil supplements support heart health, University of California Irvine (UCI) scientists have found, in a study carried out in frogs, that the fatty acids fish oils contain are vitally important to the developing brain. In the study, which was published in the April 15, 2015 issue of The Journal of Neuroscience, UCI neurobiologists report that dietary deficiencies in the type of fatty acids found in fish and other foods can limit brain growth during fetal development and early in life. The article is titled “Impact of Maternal n-3 Polyunsaturated Fatty Acid Deficiency on Dendritic Arbor Morphology and Connectivity of Developing Xenopus laevis Central Neurons In Vivo.” The findings suggest that women maintain a balanced diet rich in these fatty acids for themselves during pregnancy and for their babies after birth. Dr. Susana Cohen-Cory, Professor of Neurobiology & Behavior at UCI, and colleagues identified, for the first time, how deficits in what are known as n-3 polyunsaturated fatty acids cause molecular changes in the developing brain that result in constrained growth of neurons and the synapses that connect them. These n-3 polyunsaturated fatty acids are precursors of docosahexaenoic acid, or DHA (image), which plays a key role in the healthy creation of the central nervous system. In their study, which used female frogs and tadpoles, the UCI researchers were able to see how DHA-deficient brain tissue fostered poorly developed neurons and limited numbers of synapses, the vital conduits that allow neurons to communicate with each other.

High Levels of Corneal-Nerve-Cutting-Related Neuropeptide Substance P Disable T Regulatory Cells and Triple Rejection Rate of Second Corneal Transplants Versus First; Drugs Exist to Block Substance P

University of Texas (UT) Southwestern Medical Center ophthalmologists have identified an important cause of why secondary corneal transplants are rejected at triple the rate of first-time corneal transplants. The cornea, the most frequently transplanted solid tissue, has a first-time transplantation success rate of about 90 percent. But second corneal transplants undergo a rejection rate three times that of first transplants. "Understanding why these rejections occur is important to further improving the ways in which corneal transplants are performed," said the study's senior author Dr. Jerry Niederkorn, Professor and Vice Chair of Research of Ophthalmology, and Professor of Microbiology. "In the future, ophthalmologists may be able to implement processes, and eventually prescribe medications, that can lower the rates of rejection." More than 40,000 transplants are performed annually to replace the cornea, the clear outer lens at the front of the eye, with tissue from a donor. Most corneal transplants are done to correct severe visual impairments caused by keratoconus, a condition in which the normally dome-shaped cornea progressively thins and becomes cone-shaped, according to the American Academy of Ophthalmology. The high success rate of first-time corneal transplants is attributed to a process called immune privilege, which allows transplants to be successfully performed without matching the donor tissue to that of the recipient, as is required for organ transplants. Although immune privilege accounts for the initial high success rate, it can occasionally fail, leading to the rejection of corneal transplants in approximately 10 percent of patients. In patients requiring a second transplant, the incidence of immune rejection rises to almost 70 percent.