Sunday, November 13, 2016
Glia were once thought to simply be passive, supporting cells for neurons. But scientists now know they are involved in everything from metabolism to neurodegeneration. A growing body of evidence points to their key role in pain. In a study published today in Science, researchers at the Medical University of Vienna report that glia are involved in long-term potentiation (LTP), or the strengthening of synapses, in pain pathways in the spinal cord.
Neuroscientists Timothy Bliss and Terje Lømo first described LTP in the hippocampus, a brain area involved in memory, in the 1970s. Since then scientists have been meticulously studying the role this type of synaptic plasticity—the ability of synapses to change in strength—plays in learning and memory. More recently, researchers discovered that LTP could also amplify pain in areas where injuries or inflammation occur. "We sometimes call this a 'memory trace of pain' because the painful insult may lead to subsequent hypersensitivity to painful stimuli, and it was clear that synaptic plasticity can play a role here," says study co-author Jürgen Sandkühler, a neuroscientist also at the Medical University of Vienna. But current models of how LTP works could not explain why discomfort sometimes becomes widespread or experienced in areas a person has never felt it before, he adds.
Saturday, November 12, 2016
Lindley, a neurobiologist, is about to begin the first study ever to directly compare cannabis with an opioid painkiller (in this case, oxycodone) for treating people with chronic pain. She got a grant for this research two years ago, but it has taken that much time to meet all the requirements for working with a drug the federal government still considers highly dangerous.
Before it's given to patients, the marijuana will be kept inside steel narcotics lockers bolted to the wall in a room with surveillance cameras and a combination keypad on the door. Each locker has tamper-proof hinges and requires two keys—each held by a different person. If someone puts the wrong key in one of the locks, it will become inoperable and have to be drilled out.
All this is necessary to comply with rules imposed by the Drug Enforcement Agency to make sure drugs meant for research don't end up on the street, says Heike Newman, a senior regulatory manager at the University of Colorado's Anschutz Medical Campus, where Lindley's study will take place. Newman's job is to help researchers with the paperwork they need to file with various government agencies to get approval for their studies. She says the lockers and renovations to the storage room cost the university about $15,000.
Sunday, November 06, 2016
"These aren't wimps. These people are injecting all sorts of crazy crap into their arms. … But they were finding this excruciating," Hutchinson says. "It just fascinated me." The participants were taking enormous doses of narcotics. How could they experience such exaggerated pain?
The experiment was Hutchinson's first encounter with a perplexing phenomenon called opioid-induced hyperalgesia (OIH). At high doses, opioid painkillers actually seem to amplify pain by changing signaling in the central nervous system, making the body generally more sensitive to painful stimuli. "Just imagine if all the diabetic medications, instead of decreasing blood sugar, increased blood sugar," says Jianren Mao, a physician and pain researcher at Massachusetts General Hospital in Boston who has studied hyperalgesia in rodents and people for more than 20 years.
But how prevalent hyperalgesia is, and whether it plays a role in the U.S. epidemic of opioid abuse and overdose, is unclear. A lack of reliable testing methods and a series of contradictory papers have created believers and skeptics. A few researchers, like Mao, think hyperalgesia is an underappreciated puzzle piece in the opioid epidemic—a force that can pile on pain, drive up doses, and make it harder for chronic users to come off their drugs. Some of those researchers are looking for ways to turn down hyperalgesia, to help patients function on lower doses of their oxycodone, for example, or make it easier to taper off it altogether. Others see OIH as an oddity in the literature—real, and a powerful clue to the workings of pain pathways, but unlikely to tighten the grip of opioids on most patients. Hutchinson thinks the majority of physicians are either unaware of hyperalgesia or unconvinced of its importance. "I think if you surveyed prescribers of opioids, they would be divided probably 60–40."
Thursday, October 27, 2016
But there's a reason your doctor isn't giving you a sugar pill and telling you it's a new wonder drug. The thinking has been that you need to actually believe that you're taking a real drug in order to see any benefits. And a doctor intentionally deceiving a patient is an ethical no-no.
So placebos have pretty much been tossed in the "garbage pail" of clinical practice, says Ted Kaptchuk, director of the Program for Placebo Studies and the Therapeutic Encounter at Beth Israel Deaconess Medical Center. In an attempt to make them more useful, he's been studying whether people might see a benefit from a placebo even if they knew it was a placebo, with no active ingredients. An earlier study found that so-called "open-label" or "honest" placebos improved symptoms among people with irritable bowel syndrome.
And Kaptchuk and his colleagues found the same effect among people with garden-variety lower back pain, the most common kind of pain reported by American adults.
The study included 83 people in Portugal, all of whom had back pain that wasn't caused by cancer, fractures, infections or other serious conditions. All the participants were told that the placebo was an inactive substance containing no medication. They were told that the body can automatically respond to placebos, that a positive attitude can help but isn't necessary and that it was important to take the pills twice a day for the full three weeks.
Wednesday, October 26, 2016
The results "add to a growing body of research showing that animals communicate distress and are affected by the distress of others," says neuroscientist Inbal Ben-Ami Bartal of the University of California, Berkeley.
Neuroscientist Andrey Ryabinin and colleagues didn't set out to study pain transfer. But the researchers noticed something curious during their experiments on mice who were undergoing alcohol withdrawal. Mice in the throes of withdrawal have a higher sensitivity to pokes on the foot. And surprisingly, so did these mice's perfectly healthy cagemates. "We realized that there was some transfer of information about pain" from injured mouse to bystander, says Ryabinin, of Oregon Health & Sciences University in Portland.
When mice suffered from alcohol withdrawal, morphine withdrawal or an inflaming injection, they become more sensitive to a poke in the paw with a thin fiber — a touchy reaction that signals a decreased pain tolerance. Mice that had been housed in the same cage with the mice in pain also grew more sensitive to the poke, Ryabinin and colleagues found. These bystander mice showed other signs of heightened pain sensitivity, such as quickly pulling their tails out of hot water and licking a paw after an irritating shot.
The results are compelling evidence for the social transmission of pain, says neuroscientist Christian Keysers of the Netherlands Institute for Neuroscience in Amsterdam.
Monday, October 24, 2016
How drugs intended for patients ended up in the hands of illegal users: ‘No one was doing their job’ - The Washington Post
The Drug Enforcement Administration targeted these middlemen for a simple reason. If the agency could force the companies to police their own drug shipments, it could keep millions of pills out of the hands of abusers and dealers. That would be much more effective than fighting "diversion" of legal painkillers at each drugstore and pain clinic.
Many companies held back drugs and alerted the DEA to signs of illegal activity, as required by law. But others did not.
Collectively, 13 companies identified by The Washington Post knew or should have known that hundreds of millions of pills were ending up on the black market, according to court records, DEA documents and legal settlements in administrative cases, many of which are being reported here for the first time. Even when they were alerted to suspicious pain clinics or pharmacies by the DEA and their own employees, some distributors ignored the warnings and continued to send drugs.
"Through the whole supply chain, I would venture to say no one was doing their job," said Joseph T. Rannazzisi, former head of the DEA's Office of Diversion Control, who led the effort against distributors from 2005 until shortly before his retirement in 2015. "And because no one was doing their job, it just perpetuated the problem. Corporate America let their profits get in the way of public health."
A review of the DEA's campaign against distributors reveals the extent of the companies' role in the diversion of opioids. It shows how drugs intended for millions of legitimate pain patients ended up feeding illegal users' appetites for prescription narcotics. And it helps explain why there has been little progress in the U.S. opioid epidemic, despite the efforts of public-health and enforcement agencies to stop it.
But there was a time when fentanyl was almost exclusively used by a very small group, and it had nothing to do with Margaret Wente's idea of a "typical drug addict" or poverty or organized crime. What the general public is oblivious to—but the medical community knows—is how fentanyl addiction took its roots in anesthesiology before it made its way into the mainstream.
Dr. Ethan Bryson, associate professor in the anesthesia and psychiatry departments at the Icahn School of Medicine at Mount Sinai, New York, believes it was anesthesiologists who, familiar with fentanyl's pharmacology and abuse potential, first began misusing the opioid.
"If you look at the history of morphine, cocaine, and heroin, these were all drugs which were initially developed for legitimate medical purposes, but subsequently became recreational pharmaceuticals," Bryson told VICE. "They were all experimented on with people with that access. That's well documented in history."
Wednesday, October 19, 2016
When consumed, ghost peppers and other superhots provoke extreme reactions. "Your body thinks it's going to die," as Louisiana pepper grower Ronald Primeaux told the AP in October. "You're not going to die."
But, demonstrated by a rare though severe incident reported recently in the Journal of Emergency Medicine, superhot peppers can cause bodily harm. A 47-year-old man, unnamed in the case study, attempted a super-spicy feat — eating a hamburger served with a ghost pepper puree — and tore a hole in his esophagus.
The root from northern Cameroon had such high levels of a painkiller called tramadol that mice given an extract and placed on a hot plate didn't feel their feet burning at first.
A year later, German rivals came up with a different explanation for the unusual plant. Inexpensive, imported tramadol is so heavily abused in northern Cameroon that it seeps from human and animal waste into the groundwater and soil, where vegetation absorbs it, wrote Michael Spiteller and Souvik Kusari, chemists at the University of Dortmund.
Farmers in Northern Cameroon told the researchers that they take double or triple the safe dosage, and feed tramadol to cattle to help them pull plows through the scorching afternoon sun.
Thursday, October 13, 2016
That statistic has been steadily declining ever since. Today, about 11.5 percent of men between the ages of 24-54 are neither employed nor looking for a job. Economists say that these people are "out of the labor force" — and they don't figure into statistics like the unemployment rate.
This demographic trend has been the subject of much noise and consternation lately. Nicholas Eberstadt, a demographer at the conservative American Enterprise Institute, calls the development a "quiet catastrophe: the collapse, over two generations, of work for American men."
Eberstadt concedes that he can't pinpoint the precise causes, but he implies that the problem, at its root, emanates from some kind of moral or societal dysfunction.
"Time-use surveys suggest [these men] are almost entirely idle," Eberstadt wrote in a Wall Street Journal op-ed a few weeks ago. "Unlike in the past, the U.S. is now evidently rich enough to carry them, after a fashion," he added.
Princeton professor Alan Krueger, a former chief economist at the Department of Labor and former chairman of Obama's Council of Economic Advisers, has taken a look at the same data — but he came away with a different conclusion.
What stood out to him is that a lot of these men say they are in considerable pain.
In a recently released draft of his paper, which he will present at a Federal Reserve conference in Boston on Friday, Krueger finds that 44 percent of male, prime-age labor force dropouts say they took pain medication the day prior — which is more than twice the rate reported by employed men.
Wednesday, October 12, 2016
"It's an amazing result," says Harold Zakon, an evolutionary neurobiologist at the University of Texas, Austin, who was not involved with the work. "This study points us to important areas … that might be targeted to reduce this type of pain."
Naked mole rats are just plain weird. They live almost totally underground in coloniesstructured like honey bee hives, with hundreds of workers servicing a single queen and her few consorts. To survive, they dig kilometers of tunnels in search of large underground tubers for food. It's such a tough life that—to conserve energy—this member of the rodent family gave up regulating its temperature, and they are able to thrive in a low-oxygen, high–carbon dioxide environment that would suffocate or be very painful to humans. "They might as well be from another planet," says Thomas Park, a neuroscientist at the University of Illinois, Chicago.
Gary Lewin, a neuroscientist at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association in Berlin, began working with naked mole rats because a friend in Chicago was finding that the rodent's pain fibers were not the same as other mammals'. In 2008, the studies led to the finding that naked mole rats didn't feel pain when they came into contact with acid and didn't get more sensitive to heat or touch when injured, like we and other mammals do. Lewin was hooked and has been raising the rodents in his lab ever since. They are a little more challenging than rats or mice, he notes, because with just one female per colony producing young, he never really has quite enough individuals for his studies.
So instead of studying the whole animals, he began isolating single nerve cells from the mole rats and investigating them in lab dishes to track the molecular basis of the rodent's pain insensitivity. The pain pathway is kicked off when a substance called nerve growth factor is released by injured or inflamed cells. This factor binds to a protein on the pain-cell surface, a so-called receptor named TrkA, which relays the "pain" message throughout the cell. In us and other mammals, that message increases the activity of a molecular pore, called the TRPV1 ion channel, causing the cell to become more sensitive to touch or heat. "So the cell says 'It hurts more,'" Lewin explains.
But that doesn't happen in naked mole rats. Lewin evaluated the workings of the animal's pain pathway components by mixing them with those of standard rats and putting the combinations in immature frog eggs. For example, the naked mole rat TRPV1 channel sensitized the egg to acid and heat when the rat TrkA was put into the egg cell with it. Thus, Lewin and his colleagues narrowed down the breakdown in this pathway to the TrkA receptor itself. The naked mole rat version of TrkA failed to activate the ion channel as efficiently as the rat version of TrkA, Lewin and his colleagues reveal today in Cell Reports.
Saturday, October 08, 2016
The nature of our old-age ailments has changed in recent years. The study, published this week in The Lancet and conducted by the Institute for Health Metrics and Evaluation at the University of Washington, uses a metric called "Disability Adjusted Life Years." DALYs, as they're abbreviated, combine the number of years of life a person loses if they die prematurely with the amount of time they spend living with a disability. Think of it as time you didn't spend living your #bestlife—because you were sick or dead.
In rich countries, the number one cause of these DALYs is not surprising: ischemic heart disease, which is associated with well-known Western issues like high cholesterol and obesity. But the number two condition is a little strange: plain, old-fashioned, ever-present, low back and neck pain.
Even when you include poor and middle-income countries, low back and neck pain went from ranking 12th as a cause of DALYs globally in 1990 to ranking fourth in 2015, the most recent year. In most countries, it was the leading cause of disability. DALYs from low back and neck pain increased by more than 17 percent from 2005.
The things that make us low-level miserable are now more likely to be simple aches and pains, rather than frightening, communicable diseases like diarrhea. That's encouraging, but it's still a little sad. People all over the world increasingly live long, great lives, only to spend their golden years slathered in IcyHot.
Monday, September 19, 2016
Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse - National Academy of Sciences
Saturday, September 10, 2016
Saturday, September 03, 2016
Saturday, August 20, 2016
Those attempts were doomed to failure because all opioid drugs interact with the brain in the same way. They dock to a specific neural receptor, the mu-opioid receptor, which controls the effects of pleasure, pain relief and need.
Now scientists are trying to create opioid painkillers that give relief from pain without triggering the euphoria, dependence and life-threatening respiratory suppression that causes deadly overdoses.
That wasn't thought possible until 2000, when a scientist named Laura Bohn found out something about a protein called beta-arrestin, which sticks to the opioid receptor when something like morphine activates it. When she gave morphine to mice that couldn't make beta-arrestin, they were still numb to pain, but a lot of the negative side effects of the drug were missing. They didn't build tolerance to the drug. At certain dosages, they had less withdrawal. Their breathing was more regular, and they weren't as constipated as normal mice on morphine.
Before that experiment, scientists thought the mu-opioid receptor was a simple switch that flicked all the effects of opioids on or off together. Now it seems they could be untied. "The hope is you'd have another molecule that looks like morphine and binds to the same receptor, but the way it turns the receptor on is slightly different," says Dr. Aashish Manglik, a researcher at Stanford University School of Medicine who studies opioid receptors.
After Bohn's discovery, a number of people, including a team that includes Manglik, started looking for a drug that could connect to the mu-opioid receptor in a way that avoids the negative effects of beta-arrestin.
To do that, they mapped the receptor's structure in a computer program and started looking for chemicals that would stick to it. "We tried to look for molecules that would still bind to this 3-D structure, but are as far away from morphine and codeine as possible," Manglik says.
The team ran 3 million possibilities through the computer and picked the 23 best candidates to test in a lab. One chemical, PZM21, seems to do what they hoped: Turn the opioid receptor on without using much beta-arrestin. They report their findings in Nature on Wednesday.
Schmidt believes we could learn something from this. By trade, he is an entomologist, an expert on the Hymenoptera order — wasps, bees and ants — but his interest in this insect ritual was not merely academic. He has two teenage boys, and, on this particular morning at least, I found him wondering whether they might benefit from a pain ritual to help introduce them to adulthood.
"I mean, it wouldn't kill them," Schmidt said. "And I think that may be the key to the whole thing: It can't kill you and yet something very real is happening."
It was a bit before 7:30 on a windy weekday morning in Tucson, and Schmidt had just dropped off his 14-year-old at school. At 69, Schmidt has a head of red hair that stubbornly refuses to go gray and a boyish face that glints of mischief. We were driving in his 1999 Toyota Corolla down a road that may have been a desert highway or a city thoroughfare: My East Coast eyes couldn't tell the difference. We pulled up to a traffic light, next to a giant saguaro cactus whose short, upturned arm gave it the look of a crossing guard gesturing us to stop.
Schmidt's new book, "The Sting of the Wild: The Story of the Man Who Got Stung for Science," weaves his theories about stinging insects through a narrative of his personal experiences digging in the dirt. For many readers, the highlight of the book will be the appendix, his celebrated Pain Scale for Stinging Insects, which rates the pain level of dozens of insect stings, an index he created mostly by firsthand experience, either by suffering stings incidentally during field research or, in some cases, by inducing them.
Because stings of the same magnitude don't necessarily feel the same, Schmidt has written haiku-like descriptions for each of the 83 sting entries:
Anthophorid bee, Pain Level 1, "Almost pleasant, a lover just bit your earlobe a little too hard."
Maricopa harvester ant, Level 3, "After eight unrelenting hours of drilling into that ingrown toenail, you find the drill wedged into the toe."
Termite-raiding ant, Level 2, "The debilitating pain of a migraine contained in the tip of your finger."
Club-horned wasp, Level 0.5, "Disappointing. A paper clip falls on your bare foot."
Tuesday, August 09, 2016
Her employer paid for a nerve block that helped temporarily, numbing her lower back, but she could not afford more injections or physical therapy. A decade later, the pain radiates to her right knee and remains largely unaddressed, so deep and searing that on a recent day she sat stiffly on her couch, her curtains drawn, for hours.
The experience of African-Americans, like Ms. Lewis, and other minorities illustrates a problem as persistent as it is complex: Minorities tend to receive less treatment for pain than whites, and suffer more disability as a result.
While an epidemic of prescription opioid abuse has swept across the United States, African-Americans and Hispanics have been affected at much lower rates than whites. Researchers say minority patients use fewer opioids, and they offer a thicket of possible explanations, including a lack of insurance coverage and a greater reluctance among members of minority groups to take opioid painkillers even if they are prescribed. But the researchers have also found evidence of racial bias and stereotyping in recognizing and treating pain among minorities, particularly black patients.
"We've done a good job documenting that these disparities exist," said Salimah Meghani, a pain researcher at the University of Pennsylvania. "We have not done a good job doing something about them."
Wednesday, July 27, 2016
Firefighters arrived and administered oxygen to improve her breathing, but her skin had grown gray and her lips had turned blue. As she lay on the asphalt, the paramedics slipped a needle into her arm and injected another dose of naloxone.
In a moment, her eyes popped open. Her pupils were pinpricks. She was woozy and disoriented, but eventually got her bearings as paramedics put her on a stretcher and whisked her to a hospital.
Every day across the country, hundreds, if not thousands, of people who overdose on opioids are being brought back to life with naloxone. Hailed as a miracle drug by many, it carries no health risk; it cannot be abused and, if given mistakenly to someone who has not overdosed on opioids, does no harm. More likely, it saves a life.
As a virulent opioid epidemic continues to ravage the country, with 78 people in the United States dying of overdoses every day, naloxone's use has increasingly moved out of medical settings, where it has been available since the 1970s, and into the homes and hands of the general public.
But naloxone, also known by the brand name Narcan, has also had unintended consequences. Critics say that it gives drug users a safety net, allowing them to take more risks as they seek higher highs. Indeed, many users overdose more than once, some multiple times, and each time, naloxone brings them back.
Advocates argue that the drug gives people a chance to get into treatment and turn their lives around. And, they say, few addicts knowingly risk needing to be revived, since naloxone ruins their high and can make them violently ill.
Wednesday, July 20, 2016
Eileen Chou, a public policy professor at the University of Virginia, and her collaborators began by analyzing a data set of 33,720 U.S. households and found that those with higher levels of unemployment were more likely to purchase over-the-counter painkillers. Then, using a series of experiments, the team discovered that simply thinking about the prospect of financial insecurity was enough to increase pain. For example, people reported feeling almost double the amount of physical pain in their body after recalling a financially unstable time in their life as compared with those who thought about a secure period. In another experiment, university students who were primed to feel anxious about future employment prospects removed their hand from an ice bucket more quickly (showing less pain tolerance) than those who were not. The researchers also found that economic insecurity reduced people's sense of control, which, in turn, increased feelings of pain.
Chou and her colleagues suggest that because of this link between financial insecurity and decreased pain tolerance, the recent recession may have been a factor in fueling the prescription painkiller epidemic. Other experts are cautious about taking the findings that far. "I think the hypothesis [that financial stress causes pain] has a lot of merit, but it would be helpful to see additional rigorous evidence in a real-world environment," says Heather Schofield, an economist at the University of Pennsylvania who was not involved in the study. Given that stress in general is well known to increase feelings of pain, further research is needed to disentangle financial anxiety from other sources of pressure.
Friday, July 15, 2016
Wednesday, July 06, 2016
Though Pfizer does not sell many opioids compared with other industry leaders, its action sets it apart from companies that have been accused of fueling an epidemic of opioid misuse through aggressive marketing of their products.
Pfizer has agreed to disclose in its promotional material that narcotic painkillers carry serious risk of addiction — even when used properly — and promised not to promote opioids for unapproved, "off-label" uses such as long-term back pain. The company also will acknowledge there is no good research on opioids' effectiveness beyond 12 weeks.
The terms of the agreement were reached with the city of Chicago, which two years ago sued five other opioid manufacturers over alleged misleading marketing of opioids. An announcement of the agreement is expected Wednesday. Pfizer has also been aiding the city's investigation and lawsuit.
Thursday, June 23, 2016
The pills helped ease his pain, but they also caused him to withdraw from his wife, his two children and social life.
"Finally, my wife said, 'You do something about this or we're going to have to make some changes around here,'" said Mr. Scott, 43.
Today, Mr. Scott is no longer taking narcotics and feels better. Shortly after his wife's ultimatum, he entered a local clinic where patients are weaned off opioids and spend up to five weeks going through six hours of training each day in alternative pain management techniques such as physical therapy, relaxation exercises and behavior modification.
Mr. Scott's story highlights one patient's success. Yet it also underscores the difficulties that the Obama administration and public health officials face in reducing the widespread use of painkillers like OxyContin and Percocet. The use and abuse of the drugs has led to a national epidemic of overdose deaths, addiction and poor patient outcomes.
Thursday, June 16, 2016
Sunday, June 12, 2016
Fast relief was a pill away — Percocet, an opioid painkiller — but Dr. Alexis LaPietra did not want to prescribe it. The drug, she explained to Mrs. Pitts, 75, might make her constipated and foggy, and could be addictive. Would Mrs. Pitts be willing to try something different?
Then the doctor massaged Mrs. Pitts's neck, seeking the locus of a muscle spasm, apologizing as the patient groaned with raw, guttural ache and fear.
"Quick prick," said Dr. LaPietra, giving Mrs. Pitts a trigger point injection of Marcaine, a numbing, non-opioid analgesic.
Within seconds, Mrs. Pitts blinked in surprise, her features relaxing, as if the doctor had sponged away her pain lines. She sat up, gingerly moving her head, then beamed and impulsively hugged the doctor, vigorously and with both arms.
Since Jan. 4, St. Joseph's Regional Medical Center's emergency department, one of the country's busiest, has been using opioids only as a last resort. For patients with common types of acute pain — migraines, kidney stones, sciatica, fractures — doctors first try alternative regimens that include nonnarcotic infusions and injections, ultrasound guided nerve blocks, laughing gas, even "energy healing" and a wandering harpist.
Scattered E.R.s around the country have been working to reduce opioids as a first-line treatment, but St. Joe's, as it is known locally, has taken the efforts to a new level.
"St. Joe's is on the leading edge," said Dr. Lewis S. Nelson, a professor of emergency medicine at New York University School of Medicine, who sat on a panel that recommended recent opioid guidelines for the Centers for Disease Control and Prevention. "But that involved a commitment to changing their entire culture."
In doing so, St. Joe's is taking on a challenge that is even more daunting than teaching new protocols to 79 doctors and 150 nurses. It must shake loose a longstanding conviction that opioids are the fastest, most surefire response to pain, an attitude held tightly not only by emergency department personnel, but by patients, too.
Pain is the chief reason nearly 75 percent of patients seek emergency treatment. The E.R. waiting rooms and corridors of St. Joe's, where some 170,000 patients will be seen this year, are frequently pierced by high-pitched cries and anguished moans.
Tuesday, May 31, 2016
There's an unfortunate irony for people who rely on morphine, oxycodone, and other opioid painkillers: The drug that's supposed to offer you relief can actually make you more sensitive to pain over time. That effect, known as hyperalgesia, could render these medications gradually less effective for chronic pain, leading people to rely on higher and higher doses. A new study in rats—the first to look at the interaction between opioids and nerve injury for months after the pain-killing treatment was stopped—paints an especially grim picture. An opioid sets off a chain of immune signals in the spinal cord that amplifies pain rather than dulling it, even after the drug leaves the body, the researchers found. Yet drugs already under development might be able to reverse the effect.
It's no secret that powerful painkillers have a dark side. Overdose deaths from prescription opioids have roughly quadrupled over 2 decades, in near lockstep with increased prescribing. And many researchers see hyperalgesia as a part of that equation—a force that compels people to take more and more medication, while prolonging exposure to sometimes addictive drugs known to dangerously slow breathing at high doses. Separate from their pain-blocking interaction with receptors in the brain, opioids seem to reshape the nervous system to amplify pain signals, even after the original illness or injury subsides. Animals given opioids become more sensitive to pain, and people already taking opioids before a surgery tend to report more pain afterward.
Friday, May 27, 2016
This unsanctioned self-experiment is taking place in the kitchenette of Bautista's University of California, Berkeley, lab. The source of my discomfort is itch powder, the kind anyone can pick up at a novelty store. Its blue packet shows a cartoon man writhing in agony. Below him, in bold letters, are the words, SURPRISE THAT SPECIAL FRIEND! "It's kind of weird people can just buy this stuff on Amazon and not know what it is," Bautista says. A professor of cell and developmental biology, she's pretty sure she knows what the ingredients are: rose-hip hairs and fiberglass. Itchy stuff for sure, but there are far more distressing things in her lab.
Bautista is one of a small but growing number of researchers in the United States trying to decode the molecular secrets of itchiness. She arrived at the specialty the way many others in her field have: by studying pain. For most of medical history, itch and pain were considered variants of the same sensation — itch being just a mild form of pain. What Bautista and others have shown is that while the two share many cellular receptors and molecules, itch has its own biological infrastructure. It's these largely unmapped internal pathways that Bautista has been working to identify for the past seven years.
Wednesday, May 18, 2016
The accompanying article is excerpted from Justin O. Schmidt's new book "The Sting of the Wild: The Story of the Man Who Got Stung for Science," published this spring by John's Hopkins University Press.
Howard Evans, the great naturalist and author of the classic book "Life on a Little Known Planet," was an expert on solitary wasps. Howard, a slight, reserved man with a shock of white hair and a sparkle in his eyes, was especially fond of tarantula hawks. Once, in his dedication to the investigation of these wasps, Howard netted perhaps 10 female tarantula hawks from a flower. He enthusiastically reached into the insect net to retrieve them and, undeterred after the first sting, continued, receiving several more stings, until the pain was so great he lost all of them and crawled into a ditch and just sobbed. Later, he remarked that he was too greedy.
I know of only two people who were "voluntarily" stung by tarantula hawks. I say "voluntarily" as both were performing their duties as part of documentary films, which, among other things, "encouraged" being stung. One was a young, handsome athletic entomologist who knew of the wasps. He deftly reached into the large cylindrical battery jar and grabbed a wasp by the wings. He had her in such a position that her sting harmlessly slid off his thumbnail. We prattled for a minute or so about tarantula hawks while the camera scanned close up to the long sting as it slid harmlessly, missing its mark. Then with a great heave the wasp pulled its abdomen back and thrust the sting under the nail. Yeee…ow (I can't recall if any expressions unsuitable for general audiences were uttered), the wasp was hurled into the air and flew off unharmed. One point for wasp, zero for human.
The other was a solidly built fellow who was apparently a master of performing pain-defying acts of bravery. For the film, I was charged with catching the wasp and delivering it to the scene. Five or six tarantula hawks were easily netted from flowers of an acacia tree; unfortunately, the net snagged on some thorns, and all but one wasp escaped. The remaining wasp appeared to be a male, so I summoned the cameraman to demonstrate how males cannot sting and are harmless. I reached in and casually grabbed "him." At this point, I realized that I was holding a "her." Yeee…ow, except this time it was me. I managed to toss her back in the net, while attempting to explain my blunder and pain on camera. As I was not in the film – perhaps fortunately – the footage was relegated to some obscure studio archive, perhaps someday to be resurrected on YouTube. That episode over, the tarantula hawk was delivered to the rightful actor. He grabbed her, was stung, and showed no reaction beyond a begrudging "Ouch, that did hurt a bit." I figured the guy had no nerves. But his director then handed him a habanero pepper, a tarantula hawk of chili peppers, which he enthusiastically bit into. He became instantly speechless, convinced fire was blasting from his mouth, nose, and ears. Apparently, he did have some nerves — sensitive at least to chili peppers.
How could such a small animal as a tarantula hawk be so memorable? Several years ago I attempted to address this question in a paper entitled "Venom and the Good Life in Tarantula Hawks: How to Eat, Not Be Eaten, and Live Long." The natural history of tarantula hawks provides some insights. Tarantula hawks are the largest members of the spider wasp family Pompilidae, a family some 5,000-species strong that prey solely on spiders. The feature of tarantula hawks that makes them so special is their choice of the largest of all spiders, the fierce and intimidating tarantulas, as their target prey. The old saying "you are what you eat" rings true for tarantula hawks: if you eat the largest spiders, you become the largest spider wasps. As with other spider wasps, the female wasp provides each young with only one spider that serves as breakfast, lunch, and dinner for its entire growing life.
Thursday, May 12, 2016
"We needed to talk about congestive heart failure or diabetes or out-of-control hypertension," said Dr. Sarah Chouinard, the chief medical officer at Community Care of West Virginia, which runs primary care clinics across a big rural chunk of this state. "But we struggled over the course of a visit to get patients to focus on any of those."
Worse, she said, some of the organization's doctors were prescribing too many opioids, often to people they had grown up with in the small towns where they practiced and whom they were reluctant to deny. So four years ago, Community Care tried a new approach. It hired an anesthesiologist to treat chronic pain, relieving its primary care doctors and nurse practitionersof their thorniest burden and letting them concentrate on conditions they feel more comfortable treating.
Since then, more than 3,000 of Community Care's 35,000 patients have seen the anesthesiologist, Dr. Denzil Hawkinberry, for pain management, while continuing to see their primary care providers for other health problems. Dr. Chouinard said Community Care was doing a better job of keeping them well over all, while letting Dr. Hawkinberry make all the decisions about who should be on opioid painkillers.
"I'm part F.B.I. investigator, part C.I.A. interrogator, part drill sergeant, part cheerleader," said Dr. Hawkinberry. He is also a recovering opioid addict who has experienced the difficulties of the drugs himself.
Even for people with access to the best doctors, it is hard to safely control chronic pain. Community Care is trying to do so for a disproportionately poor population, in a state that has been ground zero for opioid abuse from the very beginning of what has become a national epidemic.
Now, the difficult work of addressing the nation's overreliance on opioids, while also treating debilitating pain, is playing out on a patient-by-patient basis, including in a patchwork of experiments like this one. About 70 percent of the 1,200 patients currently in Community Care's pain management program receive opioids as part of their treatment, which may also include nonnarcotic drugs, physical therapy, injections and appointments with a psychologist.
Many had already been on opioids "for many years before they met me," Dr. Hawkinberry said, adding that his goal is to get them on lower doses, and to try other ways of managing their pain, with his own experience as a cautionary lesson.
He became addicted to the opioid fentanyl when he was an anesthesiology resident, he said, and had to wage a legal fight to stay in the program. He relapsed four years later while working at a West Virginia hospital and underwent treatment and monitoring by a state program for doctors with addiction problems. He says he has been in recovery and has not used drugs for almost nine years.
Dr. Chouinard said that Dr. Hawkinberry's experience made him "all the better positioned to know what this is like" and well-positioned to screen for drug abuse.
Patients who are prescribed opioids have to submit urine samples at each monthly appointment and at other random times, and to bring their pills to every visit to be counted. About 500 have been kicked out of the program for violations since it started in 2012.
In addition, Community Care's pain management clinic is closely monitored by the state as one of six licensed to operate under a 2012 law meant to cut down on pill mills.
The organization's primary care providers talk frequently with Dr. Hawkinberry about the patients they share with him. Because they use the same electronic medical record system, they can keep close tabs on how their patients' pain is being treated — and he on how their other health problems, like high blood pressure, are being addressed.
Wednesday, May 11, 2016
While we welcome all proposals relevant to basic or clinical migraine research, we are particularly interested in translational projects and those related to migraine variants, childhood migraine, and chronic migraine.
Tuesday, May 10, 2016
"It's this turbulent, violent sensation that feels electric and stinging," Delp says, describing the pain at its worst. "I've run out of the building screaming like a lunatic before because it's been so bad."
Delp has erythromelalgia, a rare condition in which a person's body (typically the feet and the hands, though Delp experiences pain all over) reacts to mild warmth as though it is on fire. Mild exertion, even just standing, will set it off for Delp, which meant quitting her job of 15 years as a flight attendant. Two years of countless doctors' appointments finally got her a diagnosis in 2012, but current medications are unable to relieve pain in most patients.
"I'm pretty much a prisoner in my own home," she says. Her house in Tacoma, Washington, is kept at a chilly 58 degrees Fahrenheit, thanks to some special duct work that her husband, coincidentally in the heating and cooling business, was able to arrange. Delp spends most of her time reading, watching TV, or working on her computer to maintain an online erythromelalgia support group that she co-founded.
But, this horrific condition has handed pain researchers their most promising drug target in years. In 2004, a study of an inherited version of erythromelalgia pinpointed a mutation in a gene that directs the making of a sodium channel, called Nav1.7; sodium channels are proteins that help control the electrical excitability of neurons.
"The channel sets the sensitivity of pain-signaling neurons, and when you have those Nav1.7 mutations, the neurons fire when they shouldn't," says Stephen Waxman of Yale University School of Medicine, New Haven, US, and the Veterans Affairs Medical Center, West Haven, Connecticut. Waxman was the first to study the effects of Nav1.7 mutations in neurons.
Delp doesn't know if she has this type of mutation, but medicines that calm the channel may still give her relief. Multiple clinical trials are underway to test Nav1.7 channel blockers, not only in inherited erythromelalgia, but in more common conditions, like sciatica and trigeminal neuralgia, which both involve intense shooting pain in different parts of the body.
Patients would no longer have to wake up in the middle of the night to take their pills, Purdue told doctors. One OxyContin tablet in the morning and one before bed would provide "smooth and sustained pain control all day and all night."
On the strength of that promise, OxyContin became America's bestselling painkiller, and Purdue reaped $31 billion in revenue.
But OxyContin's stunning success masked a fundamental problem: The drug wears off hours early in many people, a Los Angeles Times investigation found. OxyContin is a chemical cousin of heroin, and when it doesn't last, patients can experience excruciating symptoms of withdrawal, including an intense craving for the drug.
The problem offers new insight into why so many people have become addicted to OxyContin, one of the most abused pharmaceuticals in U.S. history.
The Times investigation, based on thousands of pages of confidential Purdue documents and other records, found that:
• Purdue has known about the problem for decades. Even before OxyContin went on the market, clinical trials showed many patients weren't getting 12 hours of relief. Since the drug's debut in 1996, the company has been confronted with additional evidence, including complaints from doctors, reports from its own sales reps and independent research.
• The company has held fast to the claim of 12-hour relief, in part to protect its revenue. OxyContin's market dominance and its high price — up to hundreds of dollars per bottle — hinge on its 12-hour duration. Without that, it offers little advantage over less expensive painkillers.
• When many doctors began prescribing OxyContin at shorter intervals in the late 1990s, Purdue executives mobilized hundreds of sales reps to "refocus" physicians on 12-hour dosing. Anything shorter "needs to be nipped in the bud. NOW!!" one manager wrote to her staff.
• Purdue tells doctors to prescribe stronger doses, not more frequent ones, when patients complain that OxyContin doesn't last 12 hours. That approach creates risks of its own. Research shows that the more potent the dose of an opioid such as OxyContin, the greater the possibility of overdose and death.
• More than half of long-term OxyContin users are on doses that public health officials consider dangerously high, according to an analysis of nationwide prescription data conducted for The Times.
Over the last 20 years, more than 7 million Americans have abused OxyContin, according to the federal government's National Survey on Drug Use and Health. The drug is widely blamed for setting off the nation's prescription opioid epidemic, which has claimed more than 190,000 lives from overdoses involving OxyContin and other painkillers since 1999.
The internal Purdue documents reviewed by The Times come from court cases and government investigations and include many records sealed by the courts. They span three decades, from the conception of OxyContin in the mid-1980s to 2011, and include emails, memos, meeting minutes and sales reports, as well as sworn testimony by executives, sales reps and other employees.
The documents provide a detailed picture of the development and marketing of OxyContin, how Purdue executives responded to complaints that its effects wear off early, and their fears about the financial impact of any departure from 12-hour dosing.
Reporters also examined Food and Drug Administration records, Patent Office files and medical journal articles, and interviewed experts in pain treatment, addiction medicine and pharmacology.
The pain matrix is actually a cluster of regions in the brain that prior imaging studies indicated are involved in processing pain perception, including the posterior insula and the anterior cingulate cortex. This has been so broadly accepted that the signature pattern has been used to declare that emotional pain (like social rejection) and physical pain are the same thing, as far as the brain is concerned. The argument goes that something like a bad romantic breakup has the same effect on brain activity as spilling a hot cup of coffee on your shirt.
More recent studies have cast doubt on those conclusions, however. And now researchers at the University of Reading and University College London have concluded that this cluster of regions in brain is not specific to pain. It also responds to loud noises, bright lights, a strong non-painful touch (like a firm handshake), and yes, social rejection. They describe their findings in a new paper published today in JAMA Neurology.
"I wouldn't say that's it's wrong to say that the 'pain matrix' is involved in processing pain," lead author Tim Salomons (University of Reading) told Gizmodo. "What's wrong is the idea that it is specific to pain—in other words, that when you observe this pattern, you can just assume that person is in pain."
Most of these studies employ functional magnetic resonance imaging (fMRI). Unlike conventional medical MRI, which creates a static image of the brain similar to an x-ray, fMRI monitors the brain in action. When enough neurons fire together in response to a given stimulus, blood flow increases to those parts of the brain involved in processing that input. The fMRI detects this as slight increases in blood oxygen levels—the so-called BOLD response–in those different regions. The resulting gorgeous full-color images make for terrific eye candy, but they aren't actually real-time snapshots of the brain in action; rather, they're visualizations of statistical data.
So how can scientists know for sure if the pattern they're seeing is really an indicator for pain (or any other type of cognitive process)? The gold standard is cognitive neuroscience studies that involve patients with existing brain damage, according to Bradley Voytek, a neuroscientist at the University of California, San Diego, who was not involved with the study. So if you want to prove that a particular cluster of brain regions encodes pain, you must first determine that patients with damage to those regions can no longer feel pain.
Wednesday, May 04, 2016
Tuesday, May 03, 2016
That panel had concluded that the training might help stem the epidemic of overdose deaths involving prescription narcotics, or opioids. At first, Dr. Katz, who had been on the panel, thought that drug makers had pressured the F.D.A. to kill the proposal. Then an agency official told him that another group had fought the recommendation: the American Medical Association, the nation's largest doctors organization.
"I was shocked," said Dr. Katz, the president of Analgesic Solutions, a company in Natick, Mass. "You go to medical school to help public health and here we have an area where you have 15,000 people a year dying."
Now, as the White House, the Centers for Disease Control and Prevention and other federal and state agencies scramble to find solutions to the vexing opioid problem, the role of doctors is coming back to center stage. The Obama administration recently announced that it supported mandatory training for prescribers of opioids.
On Tuesday, a new F.D.A. panel of outside experts will meet to review once again whether such training should be required. The hearing will almost certainly touch off an intense debate inside the medical community and focus attention on medical groups like the A.M.A., which have resisted governmental mandates affecting how doctors practice for both ideological and practical reasons. The panel is expected to make its final recommendation on Wednesday. An F.D.A. spokeswoman said the agency now supported mandatory training.
Monday, May 02, 2016
Are there any taboo subjects left in literature? Graphic violence and sex in any of its endless variations have become mainstream. Even excretion is now explicit: Think of the unforgettable scene of Joey searching for a ring in his own shit in Jonathan Franzen's Freedom. But read almost any novel in which childbirth, one of the most universal of human events, takes place, and you will find that the actual act has been deleted. An author as celebrated for her visceral and detailed accounts of female experience as Elena Ferrante offers the following as a description, in full, of the birth of the narrator's first child in the third book of the Neapolitan novels, Those Who Leave and Those Who Stay:
I had atrocious labor pains, but they didn't last long. When the baby emerged and I saw her . . . I felt a physical pleasure so piercing that I still know no other pleasure that compares to it.
Pages later, the birth of her second child gets even less elaboration: "Everything went smoothly. The pain was excruciating, but in a few hours I had another girl."
Certain ways of avoiding a childbirth scene in contemporary fiction have become almost predictable, as clichéd as the clothes scattered on the floor in a movie rated PG-13: the frantic car ride to the hospital, followed by a jump cut to the new baby; or the played-for-laughs episode of the laboring woman screaming at her clueless husband, followed by a jump cut to the new baby. What happened to what actually happens?
My latest novel, Eleven Hours, takes place entirely during one labor and delivery in an urban hospital. I've been through childbirth twice myself, and found it the most physically painful and most transformative experience of my life. I wanted to write something I felt I hadn't read: a story that described childbirth from the inside. I wanted to depict the alterations of consciousness that come from the confrontation with great pain, and the ways in which the crisis of labor can cause a woman to find in herself previously unknown strengths. I wanted to conjure up the feeling of long waiting punctuated by intense activity. I wanted to show what it felt like to be so very close, simultaneously, to the creation of life and the possibility of death.
When Eleven Hours had been accepted for publication in the U.S. and my agent was shopping it abroad, a publisher that had taken one of my earlier books turned it down. "Sales and marketing did not feel confident they would know how to pitch it," I was told. "It's such a specific experience recounted here."
Such a specific experience? You mean, one that billions of women have been through? Did not feel confident they would know to pitch it? The novel, as I saw it, was about the severe challenge to mind and body that childbirth is for a woman, just as combat is a severe challenge to the minds and bodies of men. Would any publisher ever claim that they wouldn't know how to pitch a war narrative?
In a clinical trial published March 22 in the Journal of the American Medical Association (JAMA), subjects who underwent mindfulness training for eight weeks were more likely to report improvements in pain, lasting up to a year, compared to people who received whatever other care they chose. The study was led by Daniel Cherkin, Group Health Research Institute, Seattle, US, and Judith Turner, University of Washington, also in Seattle.
A second study, published March 16 in the Journal of Neuroscience and led by Fadel Zeidan, Wake Forest School of Medicine, Winston-Salem, North Carolina, US, and Robert Coghill, now at Cincinnati Children's Hospital, Ohio, US, hints at how mindfulness might reduce pain. The researchers showed in healthy subjects that meditation reduced acute pain independent of endogenous opioids, which account for the vast majority of other brain-based manipulations—such as the placebo effect or conditioned pain modulation.
Monday, April 18, 2016
All three botulinum toxin type A formulations are supported by level A evidence for use in upper limb spasticity, and onabotulinumtoxinA (Botox) received a level A recommendation in chronic migraine, although the magnitude of the benefit is small, according to David Simpson, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues.
The new guidance, which is the first since 2008, was published online in Neurology and reported here at the American Academy of Neurology meeting.
There are four types of botulinum toxin available on the U.S. market: three type A and one type B. Type A botulinum toxins include abobotulinumtoxinA (Dysport), incobotulinumtoxinA (Xeomin), onabotulinumtoxinA (Botox), and the lone Type B product is rimabotulinumtoxinB (Myobloc).
Simpson and colleagues reviewed the evidence for botulinum toxin in four conditions: cervical dystonia, blephrospasm, limb spasticity, and headache.
"We chose these diseases because we had a sense that there were sufficient data to show they were going to change in particular ways," Mark Hallett, MD, of the National Insitute of Neurological Disorders and Stroke, a co-author of the guideline, said during a press briefing. "We already had a feeling for what we were going to find, but we had to prove it carefully."
All three botulinum toxin type A drugs had level-A evidence supporting their use in upper limb spasticity, and abobotulinumtoxinA and onabotulinumtoxinA had level A evidence behind their use in lower limb spasticity, the researchers reported.
There was also strong level-A evidence that onabotulinumtoxinA works in chronic migraine, since the drug had been approved by the FDA in 2010 for this condition -- although the magnitude of benefit was small, Simpson said, with a 15% reduction in headache days per month compared with placebo.
Monday, April 11, 2016
A new University of Virginia study suggests that many medical students and residents are racially biased in their pain assessment, and that their attitudes about race and pain correlate with falsely-held beliefs about supposed biological differences—like black people having thicker skin, or less sensitive nerve endings than white people—more generally.
The study highlights how a confluence of mistaken attitudes—about race, about biology, and about pain—can flourish in one of the worst possible places: medical schools where the future gatekeepers of relief are trained. And it illuminates what I've called the divided state of analgesia in America: overtreatment of millions of people that feeds painkiller abuse at the same time that, with far less public attention, millions of others are systematically undertreated. Think of it as a pain gap between the haves and the have-nots, along lines of class and race.
Unfortunately, the UVA findings are neither surprising nor fundamentally new. Back in the 1990s, two studies—one in an Atlanta emergency room, the other in Los Angeles—found that white patients being treated for long bone fractures were dosed more liberally than Latino patients in L.A., and more liberally than black ones in Atlanta. The authors put forward several possible explanations of the disparity: Perhaps patients in different groups expressed pain differently, or maybe caregivers interpreted pain differently in these groups, or perhaps nurses and doctors saw pain the same way across groups but just chose to remedy pain differently.
By the late 1990s, other studies found similar disparities in cancer care, where people receiving outpatient cancer care in places that mostly served minorities were three times more likely to be under-medicated with analgesics than patients in other settings. Speculation about the causes deepened: Perhaps inadequate prescribing for minority patients resulted from concerns about potential drug abuse, or maybe minority patients had more difficulty finding pharmacies that stocked opioid prescriptions, or again perhaps there was a cultural barrier in doctor-patient understanding and assessment. Into the 2000s, additional reports have confirmed the gap—again with no agreement about any single cause.
Monday, March 28, 2016
"I'm going touch your ankle in a few places," the doctor said shortly after I was brought in. "I want you to describe the pain on a scale from 1 to 10."
He pressed down onto various parts of my foot, each one more painful than the last. And yet, the numbers I uttered barely nudged, moving up from 5 to 5.5, and then from 5.5 to 6. I never said anything higher than that.
When the X-rays were in, the doctor showed them to me and told me two things. The first was that I had fractured my ankle. The second was that there was no way the pain was less than an 8. He joked that if I had sought medical care somewhere else, somewhere less precautionary in its practices, I might have been sent away with a prescription for a mild painkiller and a bag of ice.
Machismo, the driver of so many questionable decisions made by men, is a fickle thing. Sometimes, a little bit of it — a tinge of toughness — doesn't seem to hurt. In sport, for instance. Or maybe negotiation. Other times, it turns out, it can do more harm than good. Like, say, when it comes to caring for one's health.