Posts tagged pain
Articles and news from the latest research reports.
A new promising approach in the therapy of pain
The treatment of inflammatory pain can be improved by endogenous opioid peptides acting directly in injured tissue. Scientists at the Charité – Universitätsmedizin Berlin and the Université Paris Descartes showed that pain can be successfully treated by targeting immune and nerve cells outside the brain or spinal cord. The study is published in the current issue of The FASEB Journal.
Inflammatory pain is the most common form of painful diseases. Examples are acute pain after surgery, and chronic pain as in the case of rheumatoid arthritis. However, the treatment of inflammatory pain is often difficult because it rarely responds to conventional therapies. Furthermore, opiates, such as morphine, produce serious side effects including addiction mediated in the brain, while drugs, such as ibuprofen, may cause stomach ulcers, internal bleeding, and cardiovascular complications. The activation of opiate receptors in nerve cells outside the brain or spinal cord can alleviate pain without serious side effects. This can be achieved by synthetic opiates or endogenous opioid peptides, e.g. enkephalins and endorphins. However, these peptides are rapidly inactivated by two major enzymes, aminopeptidase N (APN) and neutral endopeptidase (NEP), which limit their analgesic effects.
The aim of the research group of Prof. Halina Machelska-Stein from the Klinik für Anästhesiologie at Campus Benjamin Franklin was to prevent the breakdown of endogenous opioid peptides directly in the inflamed tissue. In an animal model, the group has shown that inflammatory pain can be alleviated if the two enzymes (APN and NEP), responsible for the inactivation of the opioid peptides, were blocked by the selective inhibitors. In preparations from immune or nerve cells, which express these enzymes, the opioid peptides were quickly broken down. This was prevented by the enzyme inhibitors, bestatin, thiorpan and P8B. As a result, the sensation of pain was either markedly reduced or completely disappeared. “Targeting of endogenous opioid peptides directly in injured tissues might be a promising strategy to treat inflammatory pain without serious side effects,” states Prof. Machelska-Stein, explaining the results of the investigation. Furthermore, blocking pain at the site of its origin may prevent excitatory mechanisms in the nervous system, which lead to the development of chronic pain.
(Source: charite.de)
Ultrasound Can Be Tweaked to Stimulate Different Sensations
A century after the world’s first ultrasonic detection device – invented in response to the sinking of the Titanic – Virginia Tech Carilion Research Institute scientists have provided the first neurophysiological evidence for something that researchers have long suspected: ultrasound applied to the periphery, such as the fingertips, can stimulate different sensory pathways leading to the brain.
And that’s just the tip of the iceberg. The discovery carries implications for diagnosing and treating neuropathy, which affects millions of people around the world.
“Ideally, neurologists should be able to tailor treatments to the specific sensations their patients are feeling,” said William “Jamie” Tyler, an assistant professor at the Virginia Tech Carilion Research Institute, who led the study published this week in PLOS ONE.
“Unfortunately, even with today’s technologies, it’s difficult to stimulate certain types of sensations without evoking others. Pulsed ultrasound allows us to selectively activate functional subsets of nerve fibers so we can study what happens when you stimulate, for example, only the peripheral fibers and central nervous system pathways that convey the sensation of fast, sharp pain or only those that convey the sensation of slow, dull, throbbing pain.”
Scientists in Australia and Austria have described a “network map” of genes involved in pain perception. The work, published in the journal PLOS Genetics should help identify new analgesic drugs.
Dr Greg Neely from the Garvan institute of Medical Research in Sydney and Professor Josef Penninger from the Austrian Academy of Sciences in Vienna had previously screened the 14,000 genes in the fruit fly genome and identified 580 genes associated with heat perception. In the current study, using a database from the US National Centre for Biotechnology Information, they noted roughly 400 equivalent genes in people, 35% of which are already suspected to be pain genes.
The map they constructed using fly and human data includes many known genes, as well as hundreds of new genes and pathways, and demonstrates exceptional evolutionary conservation of molecular mechanisms across species. This should not be surprising, as every creature must be able to identify a source of pain or danger in order to survive.
Comparing fly with human data, they could see that a particular kind of molecular signaling (phospholipid signaling), already implicated in pain processing, appeared in the pain network. Further, they demonstrated the importance of two enzymes that make phospholipids, by removing those enzymes from mice, making them hypersensitive to heat pain.
"Pain affects hundreds of millions of people, and is a research field badly in need of new approaches and discoveries," said Dr Neely.
"The fact that evolution has done such a remarkable job of conserving pain genes across species makes our fly data very useful, because much of it translates to rodents and people.
"We are able to test our hypotheses in mice, and if a gene or pathway or process functions as we predict, there is a good chance it will also apply to people.
"By cross-referencing fly data with human information already in the public domain — like gene expression profiling or genetic association studies — we know we’ll be able to pinpoint new therapeutic targets."
Where does it hurt? Pain map discovered in the human brain
Scientists have revealed the minutely detailed pain map of the hand that is contained within our brains, shedding light on how the brain makes us feel discomfort and potentially increasing our understanding of the processes involved in chronic pain.
The map, uncovered by scientists at UCL, is the first to reveal how finely-tuned the brain is to pain. Published in the Journal of Neuroscience, the study uses fMRI techniques in conjunction with laser stimuli to the fingers to plot the exact response to pain across areas of the brain.
“The results reveal that pain can be finely mapped in the brain,” said lead author Dr Flavia Mancini (UCL Institute of Cognitive Neuroscience). “While many studies have examined the brain response to pain before, our study is the first to map pain responses for the individual digits of the human hand.”
Using an fMRI brain imaging technique originally created to map the visual field, the researchers were able to distinguish the brain’s responses to painful laser heat stimuli on each finger in seven healthy participants, and to study their organisation in the brain.
This enabled the team to produce a fine-grained map showing how pain in the right hand results in certain parts of the brain being activated in the primary somatosensory cortex, an area in the left hemisphere of the brain which is involved in processing bodily information.
When comparing this pain map to ones generated by non-painful touch to the right hand, the researchers found that the two were very similar, with each map aligning with one another in each of the seven volunteers tested.
“The cells in the skin that respond to pain and the cells that respond to touch have very different structures and distributions, so we were surprised to find that the maps of pain and of touch were so similar in the brain,” said Dr Mancini. “The striking alignment of pain and touch maps suggests powerful interactions between the two systems.”
The pain maps could be used to provide markers for the location of pain in the human brain, enabling clinicians to see how patients’ brains reorganise following chronic pain.
“We know that the organisation of other sensory maps in the brain is altered in patients with chronic pain,” said Professor Patrick Haggard (UCL Institute of Cognitive Neuroscience). “Our method could next be used to track the reorganisation of brain maps that occurs in chronic pain, providing new insights into how the brain makes us feel pain. Therefore, measuring the map for pain itself is highly important.”
(Source: ucl.ac.uk)
The placebo effect goes beyond humans
Rats and humans have at least one thing in common: They both react the same way to a placebo, according to a new University of Florida study.
“That was the big finding — that the animals that expected pain relief actually got pain relief when you gave them an inert substance,” said co-author John Neubert, a pain specialist and an associate professor with the UF College of Dentistry department of orthodontics. “It helps validate our model that what we do in the rats, we believe, is a good representation of what’s being seen in humans.”
The investigation of placebo effects might lead to the identification of new therapeutic targets in the brain and of novel treatment strategies for a variety of health conditions.
A placebo response is a response seemingly to a treatment that has not actually been administered. For this study researchers looked at placebo responses in reference to pain and pain relief by evaluating how an animal responds when it “thinks” it’s getting a pain reliever.
UF researchers conditioned rats to expect morphine or salt water by giving injections of one or the other for two sessions. Then during the third session, researchers gave both groups the saline injection. About 30 to 40 percent of the group that had previously received morphine acted as if they had received morphine again and showed pain relief.
“What that means is we can then go ahead and do more mechanistic studies and do pharmacological studies targeting different receptors,” he said. “We could do different procedures and try to apply that knowledge into what we think is going on in humans.”
The two-year study published in the journal PAIN in October was the result of collaboration between Neubert and Niall Murphy, an addiction specialist and adjunct associate professor at the University of California Los Angeles. The two decided to look at placebo responses because that deals with pathways and mechanisms that relate to pain, reward and addiction.
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.”
The Hazards of Growing Up Painlessly
The girl who feels no pain was in the kitchen, stirring ramen noodles, when the spoon slipped from her hand and dropped into the pot of boiling water. It was a school night; the TV was on in the living room, and her mother was folding clothes on the couch. Without thinking, Ashlyn Blocker reached her right hand in to retrieve the spoon, then took her hand out of the water and stood looking at it under the oven light. She walked a few steps to the sink and ran cold water over all her faded white scars, then called to her mother, “I just put my fingers in!” Her mother, Tara Blocker, dropped the clothes and rushed to her daughter’s side. “Oh, my lord!” she said — after 13 years, that same old fear — and then she got some ice and gently pressed it against her daughter’s hand, relieved that the burn wasn’t worse.
“I showed her how to get another utensil and fish the spoon out,” Tara said with a weary laugh when she recounted the story to me two months later. “Another thing,” she said, “she’s starting to use flat irons for her hair, and those things get superhot.”
Tara was sitting on the couch in a T-shirt printed with the words “Camp Painless But Hopeful.” Ashlyn was curled on the living-room carpet crocheting a purse from one of the skeins of yarn she keeps piled in her room. Her 10-year-old sister, Tristen, was in the leather recliner, asleep on top of their father, John Blocker, who stretched out there after work and was slowly falling asleep, too. The house smelled of the homemade macaroni and cheese they were going to have for dinner. A South Georgia rainstorm drummed the gutters, and lightning illuminated the batting cage and the pool in the backyard.
Without lifting her eyes from the crochet hooks in her hands, Ashlyn spoke up to add one detail to her mother’s story. “I was just thinking, What did I just do?” she said.
In a world of chronic pain, individual treatment possible
An investigation into the molecular causes of a debilitating condition known as “Man on Fire Syndrome” has led Yale researchers to develop a strategy that may lead to personalized pain therapy and predict which chronic pain patients will respond to treatment.
More than a quarter of Americans suffer from chronic pain and nearly 40 percent do not get effective relief from existing drugs. In many common conditions such as diabetic neuropathy, no clear source of pain is found.
The new study published in the Nov. 13 issue of Nature Communications used sophisticated atomic modeling techniques to search for mutations found in a rare, agonizing, and previously untreatable form of chronic pain called erythromelagia, commonly referred to as “Man on Fire Syndrome.” Researchers discovered that one of those mutations seem to predicted whether a patient would respond positively to drug treatment.
“Hopefully we can use this knowledge to help chronic pain patients in more systematic ways, and not depend upon trial and error,” said Yang Yang, postdoctoral research associate in the Department of Neurology and lead author of the paper.
Naked mole-rats evolved to thrive in an acidic environment that other mammals, including humans, would find intolerable. Researchers at the University of Illinois at Chicago report new findings as to how these rodents adapted, which may offer clues to relieving pain in other animals and humans.
How does electrical stimulation affect the brain? A project by Aalto University and the University of Helsinki, launched in early 2012, studies the impact mechanism of deep brain stimulation and develops electrochemical sensors for more effective measuring of neurotransmitters in the brain. The long-term goals of the research are more specific treatment for Parkinson’s disease and many other diseases of the nervous system.