(Press-News.org) Sensing pain is extremely unpleasant and sometimes hard to bear - and pain can even become chronic. The perception of pain varies a lot depending on the context in which it is experienced. 50 years ago, neurobiologist Patrick Wall and psychologist Ronald Melzack formulated the so-called "Gate Control Theory" of pain. The two researchers proposed that inhibitory nerve cells in the spinal cord determine whether a pain impulse coming from the periphery, such as the foot, is relayed to the brain or not. A team headed by Hanns Ulrich Zeilhofer from the Institute of Pharmacology and Toxicology at the University of Zurich did now reveal which inhibitory neurons in the spinal cord are responsible for this control function: As the study published in the science journal Neuron shows, the control cells are located in the spinal dorsal horn and use the amino acid glycine as an inhibitory messenger.
The pain gate can be manipulated with viruses
With the aid of genetically modified viruses, the research group from UZH managed to specifically interfere with the function of these neurons in mice. They discovered that disabling the glycine-releasing neurons leads to an increased sensitivity to pain and signs of spontaneous pain. Moreover, Zeilhofer's team developed viruses that enable these specific pain-control cells to be activated pharmacologically. Mice treated with these viruses were less sensitive to painful stimuli than their untreated counterparts. Activating these nerve cells also alleviated chronic pain. And the surprising additional result: "Evidently, the neurons don't just control pain, but also various forms of itch," explains Zeilhofer.
How light touch controls pain
One key aspect of the Gate Control Theory is that various influences can modulate the pain-controlling neurons' activity. Based on our experience from everyday life, for instance, we know that gently rubbing or holding an injured extremity can alleviate pain in this area. According to the theory, non-painful contact with the skin is supposed to activate the inhibitory cells. Sure enough, the UZH researchers were able to verify this hypothesis and confirm that the inhibitory, glycine-releasing neurons are innervated by such touch-sensitive skin nerves.
Moreover, the pharmacologists were able to demonstrate that neurons on the superficial layers of the spinal cord, where the relay of the pain signals takes place, are primarily inhibited by glycine signals. "These three findings identify for the first the neurons and connections that underlie the Gate Control Theory of pain," sums up Zeilhofer.
Targeted therapy in humans not yet possible
Can these findings be used to treat pain? "The targeted stimulation or inhibition of particular types of neurons in humans is still a long way off and might only be possible in a few decades' time," says Zeilhofer. Another way may well reach the target sooner - namely via the receptors that are activated by the inhibitory neurons: "As these receptors are located on the neurons that relay pain signals to the brain, their specific pharmacological activation should also block pain," says Hanns Ulrich Zeilhofer. His group has already achieved promising initial results in this field, too.
INFORMATION:
Literature:
Edmund Foster, Hendrik Wildner, Laetitia Tudeau, Sabine Haueter, William T. Ralvenius, Monika Jegen, Helge Johannssen, Ladina Hösli, Karen Haenraets, Alexander Ghanem, Karl Klaus Conzelmann, Michael Bösl, Hanns Ulrich Zeilhofer (2015) Targeted ablation, silencing and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch. Neuron, in press. http://dx.doi.org/10.1016/j.neuron.2015.02.028
Contacts:
Hanns Ulrich Zeilhofer
Institute of Pharmacology and Toxicology
University of Zurich and ETH Zurich
Tel.: +41 44 63 55912
Email: zeilhofer@pharma.uzh.ch
The kidney carries out vital functions by continuously filtering the blood and excreting waste products into the urine. This is achieved by a complex system of tubules which transports the urine and regulates its composition. PhD student Annekatrin Aue, Dr. Christian Hinze and Professor Kai Schmidt-Ott of the Max Delbrück Center for Molecular Medicine (MDC) have now discovered how parts of these kidney tubules establish an inner space (lumen) and form a tight barrier against adjacent structures. The epithelial cells which line the tubules coordinate these processes ...
What does hair styling have in common with quantum computing? The braiding pattern has inspired scientists as a potential new approach to quantum calculation. The idea is to rely on a network of intersecting chains, or nanowires, containing two-dimensional quasi-particles. The way these quasi-particles evolve in space time produces a braid-like pattern. These braids could then be used as the logic gate that provides the logical function required for calculations in computers. Due to their tight assembly, such braids are much more difficult to destabilise and less error-prone. ...
A newly discovered crocodilian ancestor may have filled one of North America's top predator roles before dinosaurs arrived on the continent. Carnufex carolinensis, or the "Carolina Butcher," was a 9-foot long, land-dwelling crocodylomorph that walked on its hind legs and likely preyed upon smaller inhabitants of North Carolina ecosystems such as armored reptiles and early mammal relatives.
Paleontologists from North Carolina State University and the North Carolina Museum of Natural Sciences recovered parts of Carnufex's skull, spine and upper forelimb from the Pekin ...
"Despite all the talk about globalisation and the trend towards the expansion of the international trade space, the world is still far from frictionless or flat. There are still large national differences between countries. And these differences can greatly influence the companies' earning potential when they seek to expand."
So says Associate Professor Ingo Kleindienst from the School of Business and Social Sciences at Aarhus University. He has recently concluded a major study of 91 German-owned multinational companies and their ability to make money in foreign markets. ...
This news release is available in French. A research group at the Department of Nutritional Sciences at the University of Toronto, Faculty of Medicine has been using a rat model to see how maternal intake of above-requirement vitamins (A, D, E, and K) impact offspring's brain development and behaviour. Some of their findings were published today in the journal Applied Physiology, Nutrition, and Metabolism.
Much research on vitamins focuses on prevention of deficiencies and the toxicity of very high intakes. However, little has been done on the effect of intakes above ...
Scientists at The University of Manchester have created an enhanced surface for silicone breast implants which could reduce complications and make them less likely to be rejected by the body.
In the US alone almost 400,000 cosmetic breast augmentations and reconstructions are carried out each year, and the number is growing. Some of these cases are for reconstruction after surgery for breast cancer and can have important psychological benefits.
However, around one in five people who has a breast implant suffers from capsular contracture where scar tissue forms and ...
A new research project from the University of Copenhagen has established an effective model for the fight against the escalating burden of tooth decay among children in Asia. The model is an important tool in breaking the social inequity in oral health of children.
In developing countries, the number of children who suffer pain and discomfort in addition to missing out on school lessons is increasing. This project demonstrates that the school is a vital key to better oral health. The project also shows how it is possible to organize school oral health intervention, including ...
(March 19, 2015, Abu Dhabi, UAE) -The Tobacco Atlas, Fifth Edition ("The Atlas"), and its companion mobile app and website TobaccoAtlas.org, were unveiled today by the American Cancer Society and World Lung Foundation at the 16th World Conference on Tobacco or Health. The Atlas graphically details the scale of the tobacco epidemic; the harmful influence of tobacco on health, poverty, social justice, and the environment; the progress being made in tobacco control; and the latest products and tactics being used by the industry to protect its profits and delay and derail tobacco ...
When patients develop acute liver failure, severe complications arise rapidly after the first signs of liver disease, and patients' health can deteriorate rapidly. New research published in the American Journal of Transplantation indicates that emergency evaluations of living liver donors can be conducted safely to allow acute liver failure patients to undergo transplantation before their condition worsens.
If untreated, acute liver failure results in coma and death in more than 80 percent of cases. The only effective therapy is liver transplantation, but the deceased ...
A Los Angeles ordinance designed to curb obesity in low-income areas by restricting the opening of new fast-food restaurants has failed to reduce fast-food consumption or reduce obesity rates in the targeted neighborhoods, according to a new RAND Corporation study.
Since the fast-food restrictions were passed in 2008, overweight and obesity rates in South Los Angeles and other neighborhoods targeted by the law have increased faster than in other parts of the city or other parts of the county, according to findings published online by the journal Social Science & Medicine.
"The ...
