Posts tagged chronic pain
Articles and news from the latest research reports.
Predicting Who Will Have Chronic Pain
Abnormalities in brain axons predispose people to chronic back pain after injury
Abnormalities in the structure of the brain predispose people to develop chronic pain after a lower back injury, according to new Northwestern Medicine® research. The findings could lead to changes in the way physicians treat patients’ pain.
Most scientists and clinicians have assumed chronic back pain stems from the site of the original injury.
“We’ve found the pain is triggered by these irregularities in the brain,” said A. Vania Apkarian, senior author of the study and a professor of physiology at Northwestern University Feinberg School of Medicine. “We’ve shown abnormalities in brain structure connections may be enough to push someone to develop chronic pain once they have an injury.”
Based on MRI brain scans of people who had a new lower back injury, Northwestern scientists could predict with about 85 percent accuracy which patients’ pain would persist. The predictor was a specific irregularity or marker the scientists identified in the axons, pathways in the brain’s white matter that connect brain cells so they can communicate with each other.
The findings provide a new view of treating chronic pain, which affects nearly 100 million Americans and costs up to $635 billion a year to treat.
“We think the people who are vulnerable need to be treated aggressively with medication early on to prevent their pain from becoming chronic,” Apkarian said. “Last year, we showed people who take medication early on had a better chance of recovering. Medication does help.” Apkarian also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The research, funded by the National Institutes of Health, was published Sept. 16 in the journal Pain.
Brain abnormalities have been observed in other long-term chronic pain conditions. Apkarian’s study is the first to show brain structure abnormalities are a marker of a predisposition to the chronic pain, not a result of living with it.
The lead author of the study is Ali Mansour, M.D., formerly a postdoctoral fellow in Apkarian’s lab.
Apkarian’s research focuses on the relationship between chronic pain and the brain. One of his previous studies showed chronic pain patients lose gray matter volume over time.
Chronic pain is one of the most expensive health care conditions in the U.S. and takes an enormous toll on quality of life, yet there still is not a scientifically validated therapy for the condition. Lower back pain represents 28 percent of all causes of pain in the U.S.; about 23 percent of these patients suffer long-term pain.
The abnormalities identified in the study were found in multiple white matter axon bundles, some surrounding the nucleus accumbens and medial prefrontal cortex, two brain regions involved in processing emotion and pain. Last year, the Apkarian group showed that the physiological properties of these two regions identify which patients will persist with back pain. The new results identify a pre-existing culprit for these physiological responses to the injury.
“The brain abnormalities exist in the general population, but only those people with a back injury go on to develop the chronic pain,” Apkarian said.
For the study, Apkarian and his colleagues scanned the brains of 46 people who had an episode of lower back pain for at least four weeks and had not experienced any pain for at least one year before that. Their pain had to be rated at least five out of 10 on a pain scale for them to be included in the study.
Scientists followed the patients for a year, scanning their brains at the onset of study and one year later. After a year about half of them had improved, regardless of whether they took anything to treat the pain, and half of them continued to have pain. Those with the persistent pain had the same structural abnormalities in their white matter at the onset of the injury and after one year.
“The abnormality makes them vulnerable and predisposes them to enhanced emotional learning that then amplifies the pain and makes it more emotionally significant,” Apkarian said.
“Pain is becoming an enormous burden on the public,” said Linda Porter, the pain policy advisor at National Institute of Neurological Disorders and Stroke (NINDS) and a leader of the National Institutes of Health (NIH) Pain Consortium. “The U.S. government recently outlined steps to reduce the future burden of pain through broad-ranging efforts, including enhanced research. This study is a good example of the kind of innovative research we hope will reduce chronic pain, which affects a huge portion of the population.”
(Image: Shutterstock)
Uncovering a Healthier Remedy for Chronic Pain
Physicians and patients who are wary of addiction to pain medication and opioids may soon have a healthier and more natural alternative.
A Duke University study revealed that a derivative of DHA (docosahexaenoic acid), a main ingredient of over-the-counter fish oil supplements, can sooth and prevent neuropathic pain caused by injuries to the sensory system. The results appear online in the Annals of Neurology.
The research focused on a compound called neuroprotectin D1=protectin D1 (NPD1=PD1), a bioactive lipid produced by cells in response to external stimuli. NPD1=PD1 is present in human white blood cells, and was first identified based on its ability to resolve abdominal and brain inflammation.
"These compounds are derived from omega-3 fatty acids found in fish oil, but are 1,000 times more potent than their precursors in reducing inflammation," said Ru-Rong Ji, professor of anesthesiology and neurobiology at Duke University Medical Center and principal investigator of the study.
The team used laboratory mouse models of nerve injuries to simulate pain symptoms commonly associated with post-surgical nerve trauma. They treated these animals with chemically synthesized NPD1=PD1, either through local administration or injection, to investigate whether the lipid compound could relieve these symptoms.
Their findings revealed that NPD1=PD1 not only alleviated the pain, but also reduced nerve swelling following the injuries. Its analgesic effect stems from the compound’s ability to inhibit the production of cytokines and chemokines, which are small signaling molecules that attract inflammatory macrophages to the nerve cells. By preventing cytokine and chemokine production, the compound protected nerve cells from further damage. NPD1=PD1 also reduced neuron firing so the injured animals felt less pain.
Ji believes that the new discovery has clinical potential. “Chronic pain resulting from major medical procedures such as amputation, chest and breast surgery is a serious problem,” he said. Current treatment options for neuropathic pain include gabapentin and various opioids, which may lead to addiction and destruction of the sensory nerves.
On the other hand, NPD1=PD1 can relieve neuropathic pain at very low doses and, more importantly, mice receiving the treatment did not show signs of physical dependence or enhanced tolerance toward the lipid compound.
"We hope to test this compound in clinical trials," Ji said. The initial stages of the trial could involve DHA administration through diet and injection. "DHA is very inexpensive, and can be converted to NPD1 by an aspirin-triggered pathway," he said. The ultimate goal is to develop a safer approach to managing chronic pain.
Neurostimulation Lowers Need for Opioids in Chronic Pain
Expert Panel of Physicians and Neuroscientists Announce International Guidance on Using Neurostimulation to Significantly Reduce the Need for Opioids in Chronic Pain
Recognizing that treatment of chronic pain can be confounding, the Neuromodulation Appropriateness Consensus Committee (NACC), an international group of more than 60 leading pain specialists, has created the first consensus guidelines for the use of neurostimulation in chronic pain.
Neurostimulation is an established and growing area of pain therapy that treats nerves with electrical stimulation rather than drugs. The NACC findings, announced at the International Neuromodulation Society (INS) 11th World Congress, address provider training, patient screening, and treatment recommendations.
While the extent and suffering of chronic pain is becoming better recognized, the danger of opioids for addiction, diversion or misuse is well known. Long-term opioid use can lead to the need for escalating doses to bring relief, and raises the risk of physical dependence, overdose, weight gain, depression, and immune and hormone system dysfunction.
“Many studies contain insufficient evidence to prove the safety or effectiveness of any long-term opioid regimen for chronic pain,” said study lead author Dr. Timothy Deer, INS president-elect and director of the Center for Pain Relief in Charleston, W. Va. “Indeed, many patients discontinue long-term opioid therapy due to insufficient pain relief or adverse events.”
Neurostimulation has been shown in clinical studies to be safe and effective for properly selected patients, and is approved by the FDA to treat chronic pain of the trunk and limbs. It belongs to a family of therapies known as neuromodulation because they modulate, or alter, the function of nerves, such as nerves that may have become hypersensitized or damaged, or are otherwise sending pain signals long past the initial injury. Since the components of neurostimulators bear some resemblance to heart pacemakers, they are sometimes called pain pacemakers.
The NACC recommends neurostimulation be used earlier in the treatment of some kinds of chronic pain, such as failed back surgery syndrome and complex regional pain syndrome. A study being presented at the world congress shows neurostimulation effectiveness correlates with early use in those conditions, with the added benefit of shortening the time patients spend trying other methods and containing long-term costs of managing chronic pain.
The most common form of neurostimulation, spinal cord stimulation (SCS), was introduced in 1967 and is now implanted in some 4,000 patients annually in the United States. With SCS, appropriately selected patients who have had back and/or leg pain longer than six months often find their symptoms relieved by 50 percent or more. The therapy uses slender electrical leads placed beneath the skin along the spinal cord and connected to a compact pulse generator, about the size of a pocket watch, that sends mild current along the leads to elicit a natural biological response and limit pain messages sent to the brain. Patients try the minimally invasive technique to see if it works for them before receiving a permanent implant.
“The lessons learned over the last few decades of clinical practice have influenced neurostimulator design, placement, and programming – and added new insights into spinal anatomy and pain physiology,” said INS President Dr. Simon Thomson, consultant in in pain medicine and neuromodulation at Basildon and Thurrock University NHS Trust in the United Kingdom.
Although neurostimulation devices may seem novel at first, using electrical current to limit pain dates back to antiquity, when standing on an electric fish was one remedy. Use of modern neurostimulation devices is likely to expand as the aging populace lives longer with chronic conditions, while technological refinements and clinical evidence continue to accumulate.
“A reduction in opioid use among patients treated with spinal cord stimulation was shown in a several studies, notably a 2005 randomized controlled clinical trial led by Dr. Richard North under the auspices of the Johns Hopkins University School of Medicine,” commented INS Secretary and study co-author Dr. Marc Russo, director of the Hunter Pain Clinic in New South Wales, Australia. “Broad-based studies show that within two years, using spinal cord stimulation rather than repeat back surgery is not only a more cost-effective use of health resources, it also is correlated with higher rates of return to work.”
Consensus committee authors believe that when appropriately applied, neurostimulation to target treatment directly to nerves can improve productivity and quality of life for chronic pain patients, offering a potentially less costly and risky option than repeat surgery or long-term painkiller use. They recommend:
- Neuromodulation providers receive at least 12 hours of continuing medical education per year directly related to improving outcomes with neuromodulation, with additional mentoring by a credentialed provider at a hospital officially accredited by the Joint Commission on Accreditation of Healthcare Organizations or its equivalent.
- Spinal cord stimulation should be used early in the treatment of failed back surgery syndrome as long as there is no progression of a neurological condition requiring semi-urgent intervention.
- Patient selection decisions should be made with any clinicians who are treating co-existing conditions, who may include the patient’s primary care provider, cardiologist, or neurologist.
- Due to the emotional impact of the experience of pain, an assessment of a psychologist or psychiatrist is recommended within the first year of implant.
- Spinal cord stimulation and peripheral nerve stimulation should be considered earlier, when possible, and are recommended to be trialed in the first two years of chronic pain.
- Peripheral nerve stimulation (beyond the spine) should be reserved for patients in whom the pain distribution is primarily in a named nerve that is known to connect the area of pain. Temporary relief of the patients’ pain by an injection of local anesthetic in the nerve distribution should be seen as an encouraging sign for the use of this therapy.
- To cover an area that is not located in the distribution of a named peripheral nerve, stimulation of a peripheral nerve field with electrodes placed in the subcutaneous area just beneath the skin may give relief if stimulation from SCS does not reach this area. In many cases a hybrid of two or more of these methods may present the best chance of an acceptable outcome.
- SCS should be used as an early intervention in patients with Raynaud’s syndrome and other painful ischemic vascular disorders, which involve insufficient blood supply to part of the body. If ischemic symptoms persist despite initial surgical or reasonable medical treatment, SCS should be trialed.
- In the use of spinal cord stimulation to treat painful diabetic peripheral neuropathy, decision-making should be performed on an individualized basis, considering current diagnoses and other factors. A type of SCS that stimulates a structure at the edge of the spinal column, the dorsal root ganglion, may be most suited for this disorder.
(Source: newswise.com)
Researchers identify how cells control calcium influx
When brain cells are overwhelmed by an influx of too many calcium molecules, they shut down the channels through which these molecules enter the cells. Until now, the “stop” signal mechanism that cells use to control the molecular traffic was unknown.
In the new issue of the journal Neuron, UC Davis Health System scientists report that they have identified the mechanism. Their findings are relevant to understanding the molecular causes of the disruption of brain functioning that occurs in stroke and other neurological disorders.
"Too much calcium influx clearly is part of the neuronal dysfunction in Alzheimer’s disease and causes the neuronal damage during and after a stroke. It also contributes to chronic pain," said Johannes W. Hell, professor of pharmacology at UC Davis. Hell headed the research team that identified the mechanism that stops the flow of calcium molecules, which are also called ions, into the specialized brain cells known as neurons.
Hell explained that each day millions of molecules of calcium enter and exit each of the 100 billion neurons of the human brain. These calcium ions move in and out of neurons through pore-like structures, known as channels, that are located in the outer surface, or “skin,” of each cell.
The flow of calcium ions into brain cells generates the electrical impulses needed to stimulate such actions as the movement of muscles in our legs and the creation of new memories in the brain. The movement of calcium ions also plays a role in gene expression and affects the flexibility of the structures, called synapses, that are located between neurons and transmit electrical or chemical signals of various strengths from one cell to a second cell.
Neurons employ an unexpected and highly complex mechanism to down regulate, or reduce, the activity of channels that are permitting too many calcium ions to enter neurons, Hell and his colleagues discovered. The mechanism, which leads to the elimination of the overly permissive ion channel employs two proteins, α-actinin and the calcium-binding messenger protein calmodulin.
Located on the neuron’s outer surface, referred to as the plasma membrane, α-actinin stabilizes the type of ion channels that constitute a major source of calcium ion influx into brain cells, Hell explained. This protein is a component of the cytoskeleton, the scaffolding of cells. The ion channels that are a major source of calcium ions are referred to as Cav1.2 (L type voltage-dependent calcium channels).
The researchers also found that the calcium-binding messenger protein calmodulin, which is the cell’s main sensor for calcium ions, induces internalization, or endocytosis, of Cav1.2 to remove this channel from the cell surface, thus providing an important negative feedback mechanism for excessive calcium ion influx into a neuron, Hell explained.
The discovery that α-actinin and calmodulin play a role in controlling calcium ion influx expands upon Hell’s previous research on the molecular mechanisms that regulate the activity of various ion channels at the synapse.
One previous study proved relevant to understanding the biological mechanisms that underlie the body’s fight-or-flight response during stress.
In work published in the journal Science in 2001, Hell and colleagues reported that the regulation of Cav1.2 by adrenergic signaling during stress is performed by one of the adrenergic receptors (beta 2 adrenergic receptor) directly linked to Cav1.2.
"This protein-protein interaction ensures that the adrenergic regulation is fast, efficient and precisely targets this channel," Hell said.
"We showed that Cav1.2 is regulated by adrenergic signaling on a time scale of a few seconds, and this is mainly increasing its activity when needed, for example during danger, to make our brain work faster and better. The same channel is in the heart, where adrenergic stimulation increases channel/Ca influx activity, increasing the pacing and strength of our heart beat to meet the increased physical demands during danger."
(Source: universityofcalifornia.edu)
Persistent pain after stressful events may have a neurobiological basis
A new study led by University of North Carolina School of Medicine researchers is the first to identify a genetic risk factor for persistent pain after traumatic events such as motor vehicle collision and sexual assault.
In addition, the study contributes further evidence that persistent pain after stressful events has a specific biological basis. A manuscript of the study was published online ahead of print by the journal Pain on April 29.
“Our study findings indicate that mechanisms influencing chronic pain development may be related to the stress response, rather than any specific injury caused by the traumatic event,” said Samuel McLean, MD, MPH, senior author of the study and assistant professor of anesthesiology. “In other words, our results suggest that in some individuals something goes wrong with the body’s ‘fight or flight’ response or the body’s recovery from this response, and persistent pain results.”
The study assessed the role of the hypothalamic-pituitary adrenal (HPA) axis, a physiologic system of central importance to the body’s response to stressful events. The study evaluated whether the HPA axis influences musculoskeletal pain severity six weeks after motor vehicle collision (MVC) and sexual assault. Its findings revealed that variation in the gene encoding for the protein FKBP5, which plays an important role in regulating the HPA axis response to stress, was associated with a 20 percent higher risk of moderate to severe neck pain six weeks after a motor vehicle collision, as well as a greater extent of body pain. The same variant also predicted increased pain six weeks after sexual assault.
"Right now, if an someone comes to the emergency department after a car accident, we don’t have any interventions to prevent chronic pain from developing," McLean said. Similarly, if a woman comes to the emergency department after sexual assault, we have medications to prevent pregnancy or sexually transmitted disease, but no treatments to prevent chronic pain. This is because we understand what causes pregnancy or infection, but we have no idea what the biologic mechanisms are that cause chronic pain. Chronic pain after these events is common and can cause great suffering, and there is an urgent need to understand what causes chronic pain so that we can start to develop interventions. This study is an important first step in developing this understanding."
"In addition, because we don’t understand what causes these outcomes, individuals with chronic pain after traumatic events are often viewed with suspicion, as if they are making up their symptoms for financial gain or having a psychological reaction," McLean said. "An improved understanding of the biology helps with this stigma," McLean said.
(Source: news.unchealthcare.org)
First objective measure of pain discovered in brain scan patterns
For the first time, scientists have been able to predict how much pain people are feeling by looking at images of their brains, according to a new study led by the University of Colorado Boulder.
The findings, published today in the New England Journal of Medicine, may lead to the development of reliable methods doctors can use to objectively quantify a patient’s pain. Currently, pain intensity can only be measured based on a patient’s own description, which often includes rating the pain on a scale of one to 10. Objective measures of pain could confirm these pain reports and provide new clues into how the brain generates different types of pain.
The new research results also may set the stage for the development of methods using brain scans to objectively measure anxiety, depression, anger or other emotional states.
“Right now, there’s no clinically acceptable way to measure pain and other emotions other than to ask a person how they feel,” said Tor Wager, associate professor of psychology and neuroscience at CU-Boulder and lead author of the paper.
The research team, which included scientists from New York University, Johns Hopkins University and the University of Michigan, used computer data-mining techniques to comb through images of 114 brains that were taken when the subjects were exposed to multiple levels of heat, ranging from benignly warm to painfully hot. With the help of the computer, the scientists identified a distinct neurologic signature for the pain.
“We found a pattern across multiple systems in the brain that is diagnostic of how much pain people feel in response to painful heat.” Wager said.
Going into the study, the researchers expected that if a pain signature could be found it would likely be unique to each individual. If that were the case, a person’s pain level could only be predicted based on past images of his or her own brain. But instead, they found that the signature was transferable across different people, allowing the scientists to predict how much pain a person was being caused by the applied heat, with between 90 and 100 percent accuracy, even with no prior brain scans of that individual to use as a reference point.
The scientists also were surprised to find that the signature was specific to physical pain. Past studies have shown that social pain can look very similar to physical pain in terms of the brain activity it produces. For example, one study showed that the brain activity of people who have just been through a relationship breakup — and who were shown an image of the person who rejected them — is similar to the brain activity of someone feeling physical pain.
But when Wager’s team tested to see if the newly defined neurologic signature for heat pain would also pop up in the data collected earlier from the heartbroken participants, they found that the signature was absent.
Finally, the scientists tested to see if the neurologic signature could detect when an analgesic was used to dull the pain. The results showed that the signature registered a decrease in pain in subjects given a painkiller.
The results of the study do not yet allow physicians to quantify physical pain, but they lay the foundation for future work that could produce the first objective tests of pain by doctors and hospitals. To that end, Wager and his colleagues are already testing how the neurologic signature holds up when applied to different types of pain.
“I think there are many ways to extend this study, and we’re looking to test the patterns that we’ve developed for predicting pain across different conditions,” Wager said. “Is the predictive signature different if you experience pressure pain or mechanical pain, or pain on different parts of the body?
“We’re also looking towards using these same techniques to develop measures for chronic pain. The pattern we have found is not a measure of chronic pain, but we think it may be an ‘ingredient’ of chronic pain under some circumstances. Understanding the different contributions of different systems to chronic pain and other forms of suffering is an important step towards understanding and alleviating human suffering.”
Study finds that hot and cold senses interact
A study from the University of North Carolina School of Medicine offers new insights into how the nervous system processes hot and cold temperatures. The research led by neuroscientist Mark J. Zylka, PhD, associate professor of cell biology and physiology, found an interaction between the neural circuits that detect hot and cold stimuli: cold perception is enhanced when nerve circuitry for heat is inactivated.
“This discovery has implications for how we perceive hot and cold temperatures and for why people with certain forms of chronic pain, such as neuropathic pain, or pain arising as direct consequence of a nervous system injury or disease, experience heightened responses to cold temperatures,” says Zylka, a member of the UNC Neuroscience Center.
The study also has implications for why a promising new class of pain relief drugs known as TRPV1 antagonists (they block a neuron receptor protein) cause many patients to shiver and “feel cold” prior to the onset of hyperthermia, an abnormally elevated body temperature. Enhanced cold followed by hyperthermia is a major side effect that has limited the use of these drugs in patients with chronic pain associated with multiple sclerosis, cancer, and osteoarthritis.
Zylka’s research sheds new light on how the neural circuits that regulate temperature sensation bring about these responses, and could suggest ways of reducing such side-effects associated with TRPV1 antagonists and related drugs.
The research was selected by the journal Neuron as cover story for the April 10, 2013 print edition and was available in the April 4, 2013 advanced online edition.
This new study used cutting edge cell ablation technology to delete the nerve circuit that encodes heat and some forms of itch while preserving the circuitry that sense cold temperatures. This manipulation results in animals that were practically “blind” to heat, meaning they could no longer detect hot temperatures, Zylka explains. “Just like removing heat from a room makes us feel cold (such as with an air conditioner), removing the circuit that animals use to sense heat made them hypersensitive to cold. Physiological studies indicated that these distinct circuits regulate one another in the spinal cord.”
TRPV1 is a receptor for heat and is found in the primary sensory nerve circuit that Zylka studied. TRPV1 antagonists make patients temporarily blind to heat, which Zylka speculates is analogous to what happened when his lab deleted the animals’ circuit that detects heat: cold hypersensitivity.
Zylka emphasizes that future studies will be needed to confirm that TRPV1 antagonists affect cold responses in a manner similar to what his lab found with nerve circuit deletion.
Preventing chronic pain with stress management
For chronic pain sufferers, such as people who develop back pain after a car accident, avoiding the harmful effects of stress may be key to managing their condition. This is particularly important for people with a smaller-than-average hippocampus, as these individuals seem to be particularly vulnerable to stress. These are the findings of a study by Dr. Pierre Rainville, PhD in Neuropsychology, Researcher at the Research Centre of the Institut universitaire de gériatrie de Montréal (IUGM) and Professor in the Faculty of Dentistry at Université de Montréal, along with Étienne Vachon-Presseau, a PhD student in Neuropsychology. The study appeared in Brain, a journal published by Oxford University Press.
“Cortisol, a hormone produced by the adrenal glands, is sometimes called the ‘stress hormone’ as it is activated in reaction to stress. Our study shows that a small hippocampal volume is associated with higher cortisol levels, which lead to increased vulnerability to pain and could increase the risk of developing pain chronicity,” explained Étienne Vachon-Presseau.
As Dr. Pierre Rainville described, “Our research sheds more light on the neurobiological mechanisms of this important relationship between stress and pain. Whether the result of an accident, illness or surgery, pain is often associated with high levels of stress Our findings are useful in that they open up avenues for people who suffer from pain to find treatments that may decrease its impact and perhaps even prevent chronicity. To complement their medical treatment, pain sufferers can also work on their stress management and fear of pain by getting help from a psychologist and trying relaxation or meditation techniques.”
Research summary
This study included 16 patients with chronic back pain and a control group of 18 healthy subjects. The goal was to analyze the relationships between four factors: 1) cortisol levels, which were determined with saliva samples; 2) the assessment of clinical pain reported by patients prior to their brain scan (self-perception of pain); 3) hippocampal volumes measured with anatomical magnetic resonance imaging (MRI); and 4) brain activations assessed with functional MRI (fMRI) following thermal pain stimulations. The results showed that patients with chronic pain generally have higher cortisol levels than healthy individuals.
Data analysis revealed that patients with a smaller hippocampus have higher cortisol levels and stronger responses to acute pain in a brain region involved in anticipatory anxiety in relation to pain. The response of the brain to the painful procedure during the scan partly reflected the intensity of the patient’s current clinical pain condition. These findings support the chronic pain vulnerability model in which people with a smaller hippocampus develop a stronger stress response, which in turn increases their pain and perhaps their risk of suffering from chronic pain. This study also supports stress management interventions as a treatment option for chronic pain sufferers.
(Image: iStock)
For some, deep brain stimulation brings lasting improvement in neuropathic pain
For many patients with difficult-to-treat neuropathic pain, deep brain stimulation (DBS) can lead to long-term improvement in pain scores and other outcomes, according to a study in the February issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.
About two-thirds of eligible patients who undergo DBS achieve significant and lasting benefits in terms of pain, quality of life, and overall health, according to the report by Sandra G.J. Boccard, PhD, and colleagues of University of Oxford, led by Tipu Aziz FMedSci and Alex Green, MD. Some outcomes show continued improvement after the first year, according to the new report, which is one of the largest studies of DBS for neuropathic pain performed to date.
Most Patients Benefit from DBS for Neuropathic Pain
The authors reviewed their 12-year experience with DBS for neuropathic pain. Neuropathic pain is a common and difficult-to-treat type of pain caused by nerve damage, seen in patients with trauma, diabetes, and other conditions. Phantom limb pain after amputation is an example of neuropathic pain.
In DBS, a small electrode is surgically placed in a precise location in the brain. A mild electrical current is delivered to stimulate that area of the brain, with the goal of interrupting abnormal activity. Deep brain stimulation has become a standard and effective treatment for movement disorders such as Parkinson’s disease. Although DBS has also been used to treat various types of chronic pain, its role in patients with neuropathic pain remains unclear.
Between 1999 and 2011, that authors’ program evaluated 197 patients with chronic neuropathic pain for eligibility for DBS. Of these, 85 patients proceeded to DBS treatment. The remaining patients did not receive DBS—most commonly because they were unable to secure funding from the U.K. National Health Service or decided not to undergo electrode placement surgery.
The patients who underwent DBS were 60 men and 25 women, average age 52 years. Stroke was the most common cause of neuropathic pain, followed by head and face pain, spinal disease, amputation, and injury to nerves from the upper spinal cord (brachial plexus).
In 74 patients, a trial of DBS produced sufficient pain relief to proceed with implantation of an electrical pulse generator. Of 59 patients with sufficient follow-up data, 39 had significant improvement in their overall health status up to four years later. Thus, 66 percent of patients “gained benefit and efficacy” by undergoing DBS.
Benefits Vary by Cause; Some Outcomes Improve with Time
The benefits of DBS varied for patients with different causes of neuropathic pain. Treatment was beneficial for 89 percent for patients with amputation and 70 percent of those with stroke, compared to 50 percent of those with brachial plexus injury.
On average, scores on a 10-point pain scale (with 10 indicating the most severe pain) decreased from about 8 to 4 within the first three months, remaining about the same with longer follow-up. Continued follow-up in a small number of patients suggested further improvement in other outcomes, including quality-of-life scores.
Deep brain stimulation has long been regarded as potentially useful for patients with severe neuropathic pain that is not relieved by other treatments. However, because of the difficulties of performing studies of this highly specialized treatment, there has been relatively little research to confirm its benefits; only about 1,500 patients have been treated worldwide. The new study—accounting for about five percent of all reported patients—used up-to-date DBS technologies, imaging, and surgical techniques.
Dr. Boccard and coauthors acknowledge some important limitations of their study—especially the lack of complete patient follow-up. However, they believe their experience is sufficiently encouraging to warrant additional studies, especially with continued advances in stimulation approaches and technology. The researchers conclude, “Clinical trials retaining patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.”
(Source: eurekalert.org)
How chronic pain disrupts short term memory
A group of Portuguese researchers from IBMC and FMUP at the University of Porto has found the reason why patients with chronic pain often suffer from impaired short –term memory. The study, to be published in the Journal of Neuroscience, shows how persistent pain disrupts the flow of information between two brain regions crucial to retain temporary memories.
Chronic pain suffers often complain of short term memory’s problems. The neural mechanisms why this occurs are however not understood. Recent studies in animals showed that pain can disturb several cognitive processes as well as change the brain pathways for how we think and feel. Of the many cognitive disturbances observed the most important include problems in spatial memory, recognition memory, attention and even emotional and non-emotional decisions.
In the new article the team of researchers from the University of Porto led by Vasco Gallardo describes in a rat model of neuropathic pain how a neuronal circuit crucial for the processing of short-term memory is affected by pain. The circuit, established between the prefrontal cortex and the hippocampus, is essential for encoding and retaining temporary memories on spatial information. The researchers used multi-electrodes implanted in the brain to record neuronal activity during a behaviour dependent of spatial memory - the animals were trained in a maze where they had to choose between two alternative paths and then asked to recall their chosen path.
The results show that after a painful injury there is a significant reduction in the amount of information that passes through the circuit. This could mean a loss of ability to process information on spatial localization memory, or that those regions critical to memory are now “overwhelmed” by the painful stimuli disrupting the flow of information for memory.
According to Vasco Gallardo, the team ” has already demonstrated that peripheral nerve injury induces an instability in the spatial coding capacity of hippocampus neurons “, where is seen “a clear reduction in their capacity to encode information on the location of the animal.”
So to the author “this new work contributes to the demonstration that chronic pain induces alterations in the function of brain circuits that are not directly connected to tactile or painful processes”. So as a result of chronic pain it is seen that “are also affected neuronal circuits linked to the processing of memories and emotions, what might mean a need for larger and more integrative strategies in the treatment of painful pathologies”, says the researcher.