Posts tagged pain management
Articles and news from the latest research reports.
The future of pain relief?
Dutch burns unit trialling new virtual reality computer system that distracts patients from the agony of their wounds
The pain puzzle: Uncovering how morphine increases pain in some people
For individuals with agonizing pain, it is a cruel blow when the gold-standard medication actually causes more pain. Adults and children whose pain gets worse when treated with morphine may be closer to a solution, based on research published in the January 6 on-line edition of Nature Neuroscience.
"Our research identifies a molecular pathway by which morphine can increase pain, and suggests potential new ways to make morphine effective for more patients," says senior author Dr. Yves De Koninck, Professor at Université Laval in Quebec City. The team included researchers from The Hospital for Sick Children (SickKids) in Toronto, the Institut universitaire en santé mentale de Québec, the US and Italy.
New pathway in pain management
The research not only identifies a target pathway to suppress morphine-induced pain but teases apart the pain hypersensitivity caused by morphine from tolerance to morphine, two phenomena previously considered to be caused by the same mechanisms.
"When morphine doesn’t reduce pain adequately the tendency is to increase the dosage. If a higher dosage produces pain relief, this is the classic picture of morphine tolerance, which is very well known. But sometimes increasing the morphine can, paradoxically, makes the pain worse," explains co-author Dr. Michael Salter. Dr. Salter is Senior Scientist and Head of Neurosciences & Mental Health at SickKids, Professor of Physiology at University of Toronto, and Canada Research Chair in Neuroplasticity and Pain.
"Pain experts have thought tolerance and hypersensitivity (or hyperalgesia) are simply different reflections of the same response," says Dr. De Koninck, "but we discovered that cellular and signalling processes for morphine tolerance are very different from those of morphine-induced pain."
Dr. Salter adds, “We identified specialized cells – known as microglia – in the spinal cord as the culprit behind morphine-induced pain hypersensitivity. When morphine acts on certain receptors in microglia, it triggers the cascade of events that ultimately increase, rather than decrease, activity of the pain-transmitting nerve cells.”
The researchers also identified the molecule responsible for this side effect of morphine. “It’s a protein called KCC2, which regulates the transport of chloride ions and the proper control of sensory signals to the brain,” explains Dr. De Koninck. “Morphine inhibits the activity of this protein, causing abnormal pain perception. By restoring normal KCC2 activity we could potentially prevent pain hypersensitivity.” Dr. De Koninck and researchers at Université Laval are testing new molecules capable of preserving KCC2 functions and thus preventing hyperalgesia.
The KCC2 pathway appears to apply to short-term as well as to long-term morphine administration, says Dr. De Koninck. “Thus, we have the foundation for new strategies to improve the treatment of post-operative as well as chronic pain.”
Dr. Salter adds, “Our discovery could have a major impact on individuals with various types of intractable pain, such as that associated with cancer or nerve damage, who have stopped morphine or other opiate medications because of pain hypersensitivity.”
Cost of pain
Pain has been labelled the silent health crisis, afflicting tens of millions of people worldwide. Pain has a profound negative effect on the quality of human life. Pain affects nearly all aspects of human existence, with untreated or under-treated pain being the most common cause of disability. The Canadian Pain Society estimates that chronic pain affects at least one in five Canadians and costs Canada $55-60 billion per year, including health care expenses and lost productivity.
"People with incapacitating pain may be left with no alternatives when our most powerful medications intensify their suffering," says Dr. De Koninck, who is also Director of Cellular and Molecular Neuroscience at Institut universitaire en santé mentale de Québec.
Dr. Salter adds, “Pain interferes with many aspects of an individual’s life. Too often, patients with chronic pain feel abandoned and stigmatized. Among the many burdens on individuals and their families, chronic pain is linked to increased risk of suicide. The burden of chronic pain affects children and teens as well as adults.” These risks affect individuals with many types of pain, ranging from migraine and carpel-tunnel syndrome to cancer, AIDS, diabetes, traumatic injuries, Parkinson’s disease and dozens of other conditions.
Why Our Backs Can’t Read Braille: Scientists map sensory nerves in mouse skin
Johns Hopkins scientists have created stunning images of the branching patterns of individual sensory nerve cells. Their report, published online in the journal eLife on Dec. 18, details the arrangement of these branches in skin from the backs of mice. The branching patterns define ten distinct groups that, the researchers say, likely correspond to differences in what the nerves do and could hold clues for pain management and other areas of neurological study.
Each type of nerve cell that the team studied was connected at one end to the spinal cord through a thin, wire-like projection called an axon. On the other side of the cell’s “body” was another axon that led to the skin. The axons branched in specific patterns, depending on the cell type, to reach their targets within the skin. “The complexity and precision of these branching patterns is breath-taking,” says Jeremy Nathans, M.D., Ph.D., a Howard Hughes researcher and professor of molecular biology and genetics at the Institute for Basic Biomedical Sciences at the Johns Hopkins School of Medicine.
Scientists have learned a lot about pain, but this has not led to the discovery of many new medications to help the millions of people whose lives are affected by chronic pain.
In an effort to improve pain management, Frank Porreca, PhD, and his research group from the Department of Pharmacology at the University of Arizona College of Medicine – Tucson have been exploring new preclinical measures that may better reflect features of the human experience of pain and that can be used to find new therapies.
Relief of pain is rewarding, according to Dr. Porreca and his colleagues. They have demonstrated that treatments that relieve the unpleasant feeling of pain also activate reward circuits and reinforce behaviors that result in relief of pain. Their study, “Pain relief produces negative reinforcement through activation of mesolimbic reward/valuation circuitry,” is reported in the Nov. 26 Early Edition issue of the Proceedings of the National Academy of Sciences.
“Determining how we feel, including knowing if we are in pain, depends on a brain neural representation of information that is gathered by a multitude of sensors that monitor the body and its tissues for local temperature, blood flow, blood pressure, heart rate, pH, carbon dioxide level and other states,” says Dr. Porreca. “These ‘interoceptors’ constantly evaluate and report the state of the body to the brain, generating specific conscious sensations that tell us that we are hungry, thirsty or cold, or that something is wrong. Nociceptors are a special class of interoceptors that produce sensations of pain. They ‘sound the alarm’ to tell us that our tissues have been – or soon may be – damaged.”
Thirst, hunger, itch, cold, heat, pain and other states of imbalance are unpleasant feelings that demand a behavioral response to correct the problem, Dr. Porreca says. If you feel cold, you want to get warm; if you are thirsty, you want to drink; if you are in pain, you want relief.
What motivates an organism to respond to these feelings? Things that are essential to the life of an organism or the survival of the species, such as food or drink, are rewarding. Rewards activate neural circuits in the brain and produce pleasant and positive feelings that reinforce behaviors that increase our ability to survive, notes Dr. Porreca.
The UA researchers have demonstrated that treatments that relieve the unpleasant feeling of pain also result in activation of these same reward circuits and reinforce behaviors that result in relief of pain. The novel demonstration of pain relief as a reward provides an entirely new way to discover medicines for patients.
“The activation of the reward circuit by pain relief provides an output measure for assessment of the potential effectiveness of novel molecular targets,” Dr. Porreca explains. “The activation of these ancient and evolutionarily conserved circuits by pain relief can serve as a basis for translation of treatments that will likely be effective in humans.”