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Clinical Trials, Pain, Research, Stanford News

Pain-in-the-neck, begone! Better way to relieve chronic neck and shoulder pain?

Pain-in-the-neck, begone! Better way to relieve chronic neck and shoulder pain?

shoulderHundreds of millions of people worldwide (115 million in the United States alone) suffer from chronic pain. Stanford diagnostic radiologist Sandip Biswal, MD, calls this group “one of the largest populations in the world for medical need of any kind.” But current treatments either aren’t all that great or – in the case of opioids, which are highly effective – put patients at risk for addiction.

A pair of randomized, double-blinded clinical trials, described in a study co-authored by Biswal, former Stanford visiting scholar Charlie Koo, PhD, and several colleagues and published in Nature Scientific Reports, may point to a potential path toward more pain-free lives. In the trials, patients with chronic neck or shoulder pain were treated with three to six 90-minute sessions of either standard physical therapy – so-called transcutaneous electrical nerve stimulation,  or TENS, along with exercise and both manual and heat treatments – or a protocol designed by Koo, who now runs a facility called the Pain Cure Center in Palo Alto, California.

The new method, which Koo calls Noxipoint therapy, also employs electrical stimulation of painful areas, but in a carefully defined way: electrodes are placed precisely at both of the two attachment points for each muscle in pain, and the electrical-current jolt is brief and just enough to cause local soreness and dull, but not sharp, pain. Patients receiving the novel therapy are also told to take it easy for several days after each treatment.

In both trials, Noxipoint therapy proved superior to conventional physical therapy using TENS by close to an order of magnitude. Four weeks after their last treatment, patients given Noxipoint therapy reported substantial pain reduction, restoration of function (for example, regained range of motion) and improved quality of life, without significant side effects. Those given standard treatment reported no significant lasting improvement.

These trials are preliminary and call for confirmation in larger studies, Biswal told me. Given the pressing need for safe, lasting relief from chronic pain and the apparent success of this new method, it would be nice to see those expanded trials take place.

Previously: “People are looking for better answers”: A conversation about chronic painNational survey reveals extent of Americans living with pain and Stanford researchers address the complexities of chronic pain
Photo by Jason Trbovich

Chronic Disease, Dermatology, Immunology, Pain, Research, Science, Stanford News

Stanford researchers investigate source of scarring

Stanford researchers investigate source of scarring

2570500512_22e7fdcd48_zIf you’ve ever had a piercing that you’ve let grow closed, you’ll know that the healing process isn’t perfect. There’s almost always a little dimple to remind you of that perhaps questionable choice you may (or may not) have made during early adulthood.

Now former Stanford pediatric dermatologist Thomas Leung, MD, PhD, and developmental biologist Seung Kim, MD, PhD, have published some interesting research in Genes and Development regarding the healing and scarring process. Their findings may one day lead to advances in regenerative medicine.

As Leung, who is now an assistant professor at the University of Pennsylvania’s Perelman School of Medicine explained in an email to me:

One of the great mysteries in biology is how salamanders and worms regenerate lost body parts following trauma. In contrast to wound healing, tissue regeneration restores tissue to their original architecture and function, without a scar.  Although less dramatic, a few examples of mammalian tissue regeneration exist, including liver and digit tip regeneration.  These examples suggest that the underlying mechanisms driving tissue regeneration may still be intact in humans and perhaps we may use them for regenerative medicine.

The researchers studied how the ears of mice heal from a hole punched through the thin tissue (much like  ear piercing in humans). In many strains of mice, the holes partially fill but remain visible. In a few others, the holes heal with little perceptible scarring. Leung and Kim found that the strains of mice that heal well lack production of a protein that normally recruits white blood cells to the injury; blocking the ability of the protein, called Sdf1, to signal to the white blood cells resulted in enhanced tissue regeneration and less scarring in mice that would normally have been unable to close the hole.

Because the drug used to block Sdf1 signalling is already used clinically in humans for another purpose, Leung is hopeful that it can quickly be tested in humans struggling to heal  chronic or slow-healing wounds. He is currently designing a clinical trial to test the drug, called AMD3100.

The implications of improved wound healing with less scarring stand to benefit many more people than just those wishing away the physical evidence of a hasty cosmetic decision. Tens of millions of surgical incisions are made every year, and not all heal well. Scar tissue is less flexible than normal skin and can significantly interfere with function. In addition, people with certain medical conditions such as diabetes or poor circulation can face ongoing disability or amputation when wounds don’t heal. But the group that inspired Leung to conduct the research is especially poignant.

As Leung explained:

 The inspiration for this work was driven by our clinical experience.  At Stanford, I co-directed the Epidermolysis Bullosa (EB) clinic.  EB is a rare genetic skin disease (about eight babies are affected per million births in this country), where affected patients lack a protein that binds the skin together, resulting in fragile skin. Incidental trauma like rubbing of skin against clothing tears the skin and leaves a scar.  This endless cycle of trauma and scarring and fibrosis inevitably leads to decreased joint function and complete loss of hand function by teenage years.

My recent article for Stanford Medicine magazine and the accompanying video shed light on this devastating condition. Even a small improvement in the pain these children suffer would be a tremendous step forward. And, although Kim emphasizes that greater feats in regenerative medicine (limb regeneration, anyone?) are still years of research away, this finding shows that we’re making progress.

Previously: Limb regeneration mysteries revealed in Stanford studyTo boldly go into a scar-free future: Stanford researchers tackle wound healing and Life with epidermolysis bullosa: “Pain is my reality, pain is my normal”
Photo by The Guy with the Yellow Bike

Addiction, Anesthesiology, Chronic Disease, Pain, Stanford News, Videos

“People are looking for better answers”: A conversation about chronic pain

"People are looking for better answers": A conversation about chronic pain

2048px-Low_back_painChronic pain limits the lives of an estimated 100 million people in one way or another and costs our country half a trillion dollars per year, according to Sean Mackey, MD, PhD, chief of the Division of Pain Medicine. To address the needs of the many people suffering from back pain, the most common kind of chronic pain, Mackey and other doctors and researchers in the division recently held a free Back Pain Education Day.

The event was popular enough that all seats were filled more than a week ahead of time, and a video stream of the day’s speakers was viewed by almost 1,500 people during the conference and in the week following. Recordings of the day’s talks can now be viewed on the Division of Pain’s YouTube channel.

We don’t have a cure for chronic pain. What we have are exceptional ways [to help] people get back their lives

During a recent conversation, Mackey told me the big turn-out reflects the keen interest people living with back pain have in finding solutions. “People are looking for better answers: why they have what they have and what they can do about it,” he said. “We wanted to provide them with real-world tools that they can use to control their pain.”

Speakers at the event covered varied ground, including physical therapy approaches to pain management, new research in using acupuncture to treat pain, self-management strategies, mindfulness-based pain reduction and the important role of sleep in pain. (Recent research has shown that poor sleep can intensify and prolong pain.) One over-riding theme was the role of the brain, Mackey said, not just in terms how people experience pain, but also how it can help turn down or turn up pain.

Mackey cautions that a quick fix often isn’t possible, so people living with chronic pain need to think about long-term management. “It’s a chronic disease, like diabetes. We don’t have cures for diabetes, and we don’t have a cure for chronic pain,” he said. “What we have are exceptional ways to control the disease and ways [to help] people get back their lives.” Speaker Beth Darnall, PhD, the event co-chair, emphasized that pain psychology techniques can empower people to lessen distress and pain, and begin moving toward meaningful life goals.

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Chronic Disease, Events, Pain, Stanford News

Stanford expert on back pain: “The important thing for people to know is that it’s treatable”

BackPainSeptember is Pain Awareness Month and later this month, Stanford will host a Free Back Pain Education Day. The event, sponsored by the Division of Pain Medicine, offers community members the opportunity to come to campus and hear about current back pain management strategies and the latest research. The event will also be live-streamed via YouTube for people unable to make it in person.

In anticipation of the Sept. 13 event, I sat down with Beth Darnall, PhD, a pain psychologist at Stanford’s Pain Management Center, and one of the day’s speakers. I was interested to understand why back pain is such a critical health problem worldwide and what people living with back pain can do to manage their pain.

Back pain is a leading cause of disability in the U.S. and other countries. Why is chronic back pain so common?

I think there are many different reasons why back pain is the number one pain condition. The back seems to be the place that’s really most related to the development of chronic pain and debility from chronic pain. Pregnancy can either trigger or flare back pain, but there are a multitude of reasons: aging (there is degeneration of the spine), obesity (when people gain weight, it puts additional load on the spine), activity levels, and influence of posture. Dr. Sean Mackey will be talking about some of the reasons why back pain is the most prevalent pain condition in the world at the event.

[Back pain] is something that almost everyone will experience at some point in their lifetimes, so it’s really relevant to all of us, whether we have pain now or not.

Why have a community event about back pain now?

There has been increasing global and national attention to chronic pain in terms of its impacts and costs to society. In the United States alone, 100 million suffer from pain on a regular basis, and that is associated with costs of $635 billion dollars annually. That includes treatment costs and loss of productivity.

What we also know is that the incidence and prevalence of chronic pain has been increasing, despite the fact that theoretically, we have better treatments. So then the question is why. While we have a multitude of treatments available, we haven’t been focusing on back pain as comprehensively as we really should. We need a broader approach to the treatment of pain. This was recently outlined in the National Institute of Health’s National Pain Strategy (Note: Mackey co-chaired the oversight committee).

Some people may be under the misconception that the best way to treat back pain is simply with a pill… While medication can be one helpful component, the best way to treat back pain is with a comprehensive approach that involves self-management strategies.

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Chronic Disease, Neuroscience, Pain, Research, Stanford News

Study: Effects of chronic pain on relationships can lead to emotional distress

Study: Effects of chronic pain on relationships can lead to emotional distress

sad womanIt’s not surprising that people living with chronic pain often have high levels of emotional distress. The question that Stanford researcher Drew Sturgeon, MD, a postdoctoral pain psychology fellow in the Stanford Pain Management Center, recently aimed to determine was why. Is a patient’s depression or anger caused by his or her inability to do physical things or is it perhaps because pain can limit social relationships?

“What I hear from patients is that it’s not just that it hurts, but that the pain takes you away from things that matter to you – the things that are meaningful to you,” Sturgeon recently said.

To explore this further, Sturgeon and colleagues analyzed data from 675 patients who came into the Stanford pain clinic and filled out data sets for the national open source Collaborative Health Outcomes Information Registry, referred to as CHOIR. CHOIR is a registry that originated at the Stanford pain center to help improve the collection and reporting of data on pain.

The researchers examined both physical functioning and social satisfaction reported by chronic pain patients, since both have been shown to play a role in causing anger and depression. Their results — published online recently in the journal Pain — show that the effects of chronic pain on a patient’s social relationships can be a key trigger of depression and anger, even more so than the limits that pain can place on physical activity.

“My suspicion was that there was going to be a stronger frustration when [the pain] affects social relations,” Sturgeon told me. “Relationships are one of the strongest predictors of mood. If you’re an avid bicyclist and can no longer cycle, that’s frustrating. But if cycling is the primary source of your social relationships, that’s even more frustrating.”

“The conversation when you have a patient with chronic pain who is very depressed tends to [focus on] how we treat the pain,” he continued. “Perhaps considering how the pain is affecting the people around the patient is also important… This is something that as a field we haven’t been paying very good attention to.”

Previously: National survey reveals extent of Americans living with pain, Chronic pain: getting your head around it and Advances in pain research and treatment
Photo by rochelle hartman

Behavioral Science, Emergency Medicine, Health Disparities, Pain, Patient Care, Pediatrics, Research

Blacks, Hispanics and low-income kids with stomach aches treated differently in ERs

Blacks, Hispanics and low-income kids with stomach aches treated differently in ERs

crying-613389_1280When a child arrives in the emergency room complaining of a stomach pain, appendicitis is the last thing you want to miss, says KT Park, MD, assistant professor of pediatrics.

“The question is, ‘Does this patient have appendicitis – yes or no?,” he said. It is the most common immediate emergency that could bring a child into the emergency room with abdominal pain. If not treated in a timely manner, the appendix can burst, leading to infection or a host of other serious complications.

But kids arrive in the emergency room complaining of stomach aches all the time; most with perfectly healthy appendices. And what if you’re a doctor who has seen seven kids with more minor stomach problems one day? It might be tricky to spot that first case of appendicitis.

Unfortunately, misdiagnosis happens more often when the pediatric patient is black, Hispanic or low-income, according to a study published today in PLOS ONE led by Park and Stanford medical student Louise Wang.

“Our goal in this study is getting the word out about abdominal pain and appendicitis and the importance of the decisions made in the emergency room,” Wang said.

The researchers analyzed national data from 2 million pediatric visits to emergency rooms between 2004 and 2011 complaining primarily of abdominal pain. They found that blacks, Hispanics and low-income children were less likely to receive imaging that could help their physicians diagnose serious conditions like appendicitis. These patients were also less likely to be admitted to the hospital, but more likely to suffer perforated appendicitis, a clue that perhaps they didn’t receive adequate treatment in time, Park said. For example, low-income blacks were 65 percent more likely to have a perforated appendix compared to other children.

The study was not able to precisely determine why these disparities exist, Wang said. “What is the driving influence of these outcomes? Are these kids being mismanaged in the emergency department, or are they presenting at a later time in a more serious condition?,” she asked.

She and Park have a few ideas, based on other findings and their personal experience. Minorities and low-income families are more likely to use the emergency room as a first-stop for more minor conditions, rather than visiting their primary care doctor or pediatrician.

“This is a very delicate topic,” Park said. “Physicians are humans and there is potentially some intuitive thinking that goes on about the probabilities of various diagnoses more common in certain patient groups, potentially leading to differences in how clinicians perceive the acuity of a patient’s status.”

Appendicitis can be tricky to diagnose, a task made even harder when patients are young and unable to clearly describe their pain, Park said.

“The psychology of physicians is an area needing further evaluation,” Park said. “We have internal biases that we often are not even aware of. We want to be objective, but it’s never a black-and-white decision making tree.”

Previously: A young child, a falling cabinet, and a Life Flight rescue, New test could lead to increase of women diagnosed with heart attack and Exploring how the Affordable Care Act has affected number of young adults visiting the ER
Photo by amandacatherine

Addiction, Aging, Chronic Disease, Pain

National survey reveals extent of Americans living with pain

National survey reveals extent of Americans living with pain


Yesterday, the NIH announced a new analysis of data that examined how much pain people in America suffer. The findings, published in The Journal of Pain, were based on data from the 2012 National Health Interview Survey (NHIS), an annual survey that asks a random sample of U.S. residents a wide variety of questions about their health.

The survey results are staggering: More than half of the adults in the country (126 million) had some kind of pain, minor to severe, in the three months before the survey. About 25 million had pain every day for that time frame and about 40 million suffer from severe pain. Those with the worst pain were also most likely to have worse health in general, use more health services and have more disabilities.

The survey also looked at complementary medicine approaches people take to dealing with their pain. Natural dietary supplements topped the list, followed by deep breathing and physical exercise such as yoga, tai chi or qi gong.

Joseph Briggs, director of the National Center for Complementary and Integrative Health was quoted in an article about the new study in the Washington Post:

The number of people who suffer from severe and lasting pain is striking. . . This analysis adds valuable new scope to our understanding of pain … It may help shape future research, development and targeting of effective pain interventions, including complementary health approaches.

Another topic the WaPo article touched on, which we’ve written about here at Scope, is the link between chronic pain and prescription painkiller abuse:

The prevalence of chronic pain in America also lies at the root of an ongoing epidemic of prescription painkiller abuse. Since 1999, according to the Centers for Disease Control and Prevention, the amount of painkillers such as oxycodone and hydrocodone sold in the United States has nearly quadrupled.

Here at Stanford, the Division of Pain Medicine is sponsoring a free back pain education day on Saturday September 13. You can find out more details here.

Previously: Assessing the opioid overdose epidemicChronic pain: Getting your head around itFinding relief from lower back pain and Stanford researchers address the complexities of chronic pain
Photo by Steven Depolo

Cancer, Clinical Trials, Dermatology, Genetics, Pain, Pediatrics, Research, Stanford News

The worst disease you’ve never heard of: Stanford researchers and patients battle EB

The worst disease you've never heard of: Stanford researchers and patients battle EB

EB patient and docsI’m often humbled by my job. Well, not the job, exactly, but the physicians, researchers, and especially patients who take the time to speak with me about their goals and passions, their triumphs and fears. Their insight helps me as I struggle to interpret what goes on here at the Stanford University School of Medicine for others across the university and even around the world.

But every once in a while, an article comes along that brings me to my (emotional) knees. My article “The Butterfly Effect” in the latest issue of Stanford Medicine magazine describes the toll of a devastating skin disease called epidermoloysis bullosa on two young men and their families, as well as the determined efforts of a dedicated team of doctors and scientists to find a treatment. As a result, Stanford recently launched the world’s first stem-cell based trial aimed at correcting the faulty gene in the skin cells of patients with a severe form of the condition, which is often called EB.

I trace the path of one family as they learn, mere hours after his birth, that their son, Garrett Spaulding, has EB, which compromises the ability of the outer layers of the to stick together during friction or pressure. Patients develop large blisters and open wounds over much of their bodies. It’s incurable, fatal, and nearly indescribably painful. Paul Khavari, MD, PhD, now the chair of Stanford’s Department of Dermatology, was a young doctor at the time newborn Garrett was admitted to Lucile Packard Children’s Hospital Stanford in 1997.

“His whole body, his skin was blistered and falling off everywhere someone had touched him,” Khavari recalls in the article. “His parents were devastated, of course, at a time that was supposed to be one of the most joyful of their lives.”

Garrett’s now 18 years old, but the disease is taking its toll.

You’ll also meet Paul Martinez, one of the first participants in Stanford’s new clinical trial. He’s 32, which makes him an old man in the EB community. Unlike many EB patients, he has finished high school and completed a college degree in business marketing with a dogged determination that makes me ashamed of my petty complaints about my minor life trials. And he’s done it without relying on the pain medications essential for most EB patients. As he explains in the article:

We don’t know what it is like to not be in pain. It’s just normal for us. […] I have a very high tolerance, and don’t take any pain medication. I cherish my mind a lot. Rather than feel like a zombie, I prefer to feel the pain and feel alive.

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Addiction, Mental Health, Pain, Public Health, Technology

Student engineers unveil tamper-proof pill bottle

Student engineers unveil tamper-proof pill bottle

Pill-dispenserThe United States has been battling a prescription painkiller epidemic for years. The statistics from the Centers for Disease Control and Prevention are chilling: The number of painkillers prescribed has quadrupled since 1999; more than two million people abused painkillers in 2013; every day, 44 people die from a prescription opioid overdose.

In response, faculty at the Center for Injury Research and Policy at the Johns Hopkins Bloomberg School of Public Health issued a challenge to seniors in the university’s mechanical engineering program: build a pill bottle that would protect against theft and tampering.

One team of students came up with a design that worked so well that their team’s mentors Andrea Gielen, ScD, and Kavi Bhalla, PhD, submitted a proposal to the National Institutes of Health for further testing.

The device is about the size of a can of spray paint, much larger than the average pill bottle. It can only be opened with a special key, which pharmacists can use to refill with a month’s supply of OxyContin. A fingerprint sensor ensures only the prescribed patient can access the pills at prescribed intervals and doses. In a story on the Johns Hopkins website earlier this month, Megan Carney, one of the student engineers described how the pill dispenser works:

The device starts to work when the patient scans in his or her fingerprint. This rotates a disc, which picks up a pill from a loaded cartridge and empties it into the exit channel. The pill falls down the channel and lands on a platform where the patient can see that the pill has been dispensed. The patient then tilts the device and catches the pill in their hand.

A short video about the pill dispenser shows it in action, too. The dispenser still has to undergo additional testing, but the team hopes to bring it to market soon — and help prevent future opioid overdoses.

Previously: Unmet expectations: Testifying before Congress on the opioid abuse epidemic, The problem of prescription opioids: “An extraordinarily timely topic”, Assessing the opioid overdose epidemic, Why doctors prescribe opioids to patients they know are abusing them and Stanford addiction expert: It’s often a “subtle journey” from prescription-drug use to abuse
Photo courtesy of Johns Hopkins University

Chronic Disease, In the News, Pain, Research, Science, Stanford News

Scientific discovery could lead to treatments for chronic pancreatitis

Scientific discovery could lead to treatments for chronic pancreatitis

Pancreatitis is one of the most common gastrointestinal hospital admissions-related illness. Patients with the acute form of the disease show up at hospitals doubled over with severe abdominal pain, a swollen belly that’s tender to the touch, nausea, and vomiting.

For some patients the disease flares up then disappears. For others, it develops into an ongoing, chronic form of the disease with no known cure. Not only is it extremely painful, it also causes malnutrition and carries with it a high risk of leading to pancreatic cancer. Treatment options are pretty much limited to prescription pain killers.

This has great implication in a disease that has no active therapy with no known agents that can alter its natural devastating course

It’s known that chronic pancreatitis is marked by the uncontrolled growth of scar tissue in the pancreas known as fibrosis, which slowly destroys the organ’s ability to function. Since the pancreas is in charge of excreting enzymes to digest food, patients begin to suffer malnutrition. It’s also known that excessive alcohol consumption is the leading cause of pancreatitis but just what is happening at a molecular level to cause the fibrosis is less clear.

Now, Stanford researcher and gastroenterologist Aida Habtezion, MD, and colleagues here and at Cedars-Sinai Medical Center have published research that sheds light on what exactly is happening and could lead to treatments for the severe disease. In a story I wrote on the study, Habtezion discusses their discovery of a new molecular pathway that when blocked by an experimental pharmacological drug can slow the progression of pancreatitis in animal models and in human cells.

As Habtezion told me, her lab’s research into just how the immune cells of the pancreas behave when inflamed with pancreatitis unveiled the new pathway:

“For the first time we can show that macrophages interact with pancreatic stellate cells via a particular immune pathway, and by targeting this pathway we show a decrease in chronic pancreatitis/fibrosis progression,” she said. “This has great implication in a disease that has no active therapy with no known agents that can alter its natural devastating course.”

The hope is that researchers will now be able to develop a form of the experimental pharmacological agent used in the study to block the molecular pathway that can be given to humans. Blocking the pathway will block the scar tissue growth, and hopefully either slow the progression of the disease or reverse it altogether.

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