A technique called optogenetics has transformed neuroscience during the past 10 years by allowing researchers to turn specific neurons on and off in experimental animals. By flipping these neural switches, it has provided clues about which brain pathways are involved in diseases like depression and obsessive-compulsive disorder. "Optogenetics is not just a flash in the pan," says neuroscientist Robert Gereau of Washington University in Saint Louis. "It allows us to do experiments that were not doable before. This is a true game changer like few other techniques in science."
Since the first papers were published on optogenetics in the mid-aughts some researchers have mused about one day using optogenetics in patients, imagining the possibility of an off-switch for depression, for instance.
The technique, however, would require that a patient submit to a set of highly invasive medical procedures: genetic engineering of neurons to insert molecular switches to activate or switch off cells, along with threading of an optical fiber into the brain to flip those switches. Spurred on by a set of technical advances, optogenetics pioneer Karl Deisseroth, together with other Stanford University researchers, has formed a company to pursue optogenetics trials in patients within the next several years—one of several start-ups that are now contemplating clinical trials of the technique.
Circuit Therapeutics, founded in 2010, is moving forward with specific plans to treat neurological diseases. (It also partners with pharmaceutical companies to help them use optogenetics in animal research to develop novel drug targets for human diseases.) Circuit wants to begin clinical trials for optogenetics to treat chronic pain, a therapy that would be less invasive than applications requiring implantation deep inside the brain. Neurons affected by chronic pain are relatively accessible, because they reside in and just outside the spinal cord, an easier target than the brain. Even nerve endings in the skin might be targeted, making them much easier to reach. "In animal models it works incredibly well," says Scott Delp, a neuroscientist at Stanford, who collaborates with Deisseroth. The firm is also working to develop treatments for Parkinson's and other neurological disorders.
More ..l
http://www.scientificamerican.com/article/revolutionary-neuroscience-technique-slated-for-human-clinical-trials/
Ending chronic pain with new drug therapy | EurekAlert! Science News
A brain region controlling whether we feel happy or sad, as well as addiction, is remodeled by chronic pain, reports a new Northwestern Medicine study.
And in a significant breakthrough for the millions of Americans suffering from chronic pain, scientists have developed a new treatment strategy that restores this region and dramatically lessens pain symptoms in an animal model.
The new treatment combines two FDA-approved drugs: a Parkinson's drug, L-dopa, and a non-steroidal anti-inflammatory drug. The combined drugs target brain circuits in the nucleus accumbens and completely eliminate chronic pain behavior when administered to rodents with chronic pain. The key is administering the drugs together and shortly after an injury.
As a result of the study's findings, the scientists are pursuing a clinical trial. The treatment has the potential to prevent chronic pain if used early enough after injury, the scientists said.
The study will be published December 21 in Nature Neuroscience.
'It was surprising to us that chronic pain actually rewires the part of the brain controlling whether you feel happy or sad," said corresponding author D. James Surmeier, chair of physiology at Northwestern University Feinberg School of Medicine. "By understanding what was causing these changes, we were able to design a corrective therapy that worked remarkably well in the models. The question now is whether it will work in humans."
"The study shows you can think of chronic pain as the brain getting addicted to pain," said A. Vania Apkarian, also a corresponding author and a professor of physiology at Feinberg. "The brain circuit that has to do with addiction has gotten involved in the pain process itself."
A group of neurons thought to be responsible for negative emotions became hyper-excitable and more strongly connected with other regions of the brain linked to feeling bad within days after an injury that triggers chronic pain behavior, the study showed. It went on to show this change was triggered by a drop in dopamine, a critical neurotransmitter.
When scientists administered the non-steroidal anti-inflammatory drug and L-dopa, which raises dopamine levels, the changes in the brain were reversed and the animals' chronic pain behavior stopped.
"These results establish chronic pain cannot be viewed as a purely sensory phenomenon but instead is closely related to emotions," Apkarian said.
More ...
Patient Care: Doctors Can Ease Patient Suffering By Asking 'What's The Worst Part Of This?'
Modern medicine in the Western world relies primarily on treating existing illnesses with drugs or unnecessary procedures and a quick turnaround in the doctor's office in order to treat more people. In the midst of all this hectic chaos, doctors will skim over a patient's record and medical history, get a mere glimpse into their emotional lives, and leave mental health care to the side.
But Dr. Ronald Epstein, a University of Rochester professor, wants to change the way doctors approach their patients. Suffering is seen in all corners of hospitals and medical centers — from the emotional pain of a mother who just lost an unborn baby to an older man facing a terminal illness, yet doctors often don't address it.
In a new essay published in the Journal of the American Medical Association, Epstein and a co-author, oncologist Anthony Back of the University of Washington, reviewed medical literature on the ways doctors approach suffering. They found that an approach to suffering is rarely discussed in the medical world, and that this needs to change.
"Physicians can have a pivotal role in addressing suffering if they can expand how they work with patients," the authors wrote. "Some people can do this instinctively, but most physicians need training in how to respond to suffering — yet this kind of instruction is painfully lacking."
Epstein and Back note that physicians can improve their approach by listening to the patient and learning about his/her experience. In addition to the typical "diagnosing and treating," the authors argue that doctors should also "turn toward" the patient, and recognize their suffering. They can do that by asking questions like, "What's the worst part of this for you?" Sometimes an acknowledgment that their pain is real, and that it matters to someone, is all a patient needs to open up.
More ...
http://www.medicaldaily.com/patient-care-doctors-can-ease-patient-suffering-asking-whats-worst-part-366464
But Dr. Ronald Epstein, a University of Rochester professor, wants to change the way doctors approach their patients. Suffering is seen in all corners of hospitals and medical centers — from the emotional pain of a mother who just lost an unborn baby to an older man facing a terminal illness, yet doctors often don't address it.
In a new essay published in the Journal of the American Medical Association, Epstein and a co-author, oncologist Anthony Back of the University of Washington, reviewed medical literature on the ways doctors approach suffering. They found that an approach to suffering is rarely discussed in the medical world, and that this needs to change.
"Physicians can have a pivotal role in addressing suffering if they can expand how they work with patients," the authors wrote. "Some people can do this instinctively, but most physicians need training in how to respond to suffering — yet this kind of instruction is painfully lacking."
Epstein and Back note that physicians can improve their approach by listening to the patient and learning about his/her experience. In addition to the typical "diagnosing and treating," the authors argue that doctors should also "turn toward" the patient, and recognize their suffering. They can do that by asking questions like, "What's the worst part of this for you?" Sometimes an acknowledgment that their pain is real, and that it matters to someone, is all a patient needs to open up.
More ...
http://www.medicaldaily.com/patient-care-doctors-can-ease-patient-suffering-asking-whats-worst-part-366464
CDC Guideline for Prescribing Opioids for Chronic Pain (Guideline) - Regulations.gov
The Centers for Disease Control and Prevention (CDC) in the Department of Health and Human Services (HHS) announces the opening of a docket to obtain public comment on the draft CDC Guideline for Prescribing Opioids for Chronic Pain (Guideline). The Guideline provides recommendations regarding initiation or continuation of opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessment of risk and addressing harms of opioid use. The Guideline is intended to be used by primary care providers (e.g., family physicians or internists) who are treating patients with chronic pain (i.e., pain lasting longer than 3 months or past the time of normal tissue healing) in outpatient settings. The draft Guideline is intended to apply to patients aged 18 years of age or older with chronic pain outside of palliative and end-of-life care. The Guideline is not intended to apply to patients in treatment for active cancer. The Guideline is not a federal regulation; adherence to the Guideline will be voluntary.
Background
CDC developed the draft Guideline to provide recommendations about opioid prescribing for primary care providers who are treating adult patients with chronic pain in outpatient settings, outside of active cancer treatment, palliative care, and end-of-life care. The draft Guideline summarizes scientific knowledge about the effectiveness and risks of long-term opioid therapy, and provides recommendations for when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use. The draft Guideline identifies important gaps in the literature where further research is needed.
To develop the recommendations, CDC conducted a systematic review on benefits and harms of opioids and developed the draft Guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. CDC drafted recommendations and consulted with experts on the evidence to inform the recommendations. CDC hosted webinars in September 2015 and also provided opportunities for stakeholder and peer review of the draft Guideline. The Guideline is not a federal regulation; adherence to the Guideline will be voluntary. For additional information on prescription drug overdose, please visit http://www.cdc.gov/drugoverdose/prescribing/guideline.html.
Supporting and Related Material in the Docket
The docket contains the following supporting and related materials to help inform public comment: The Guideline; the Clinical Evidence Review Appendix; the Contextual Evidence Review Appendix; and three documents that comprise the Comment Summaries and CDC Responses (Constituent Comment Summary, Peer Review Summary, and Stakeholder Review Group Summary). The Clinical Evidence Review Appendix and the Contextual Evidence Review Appendix include primary evidence, studies, and data tables that were used by CDC to develop the recommendations in the Guideline. The Constituent Comment Summary reflects input obtained in response to webinars hosted on September 16 and September 17, 2015, during which CDC shared an overview of the development process and draft recommendation statements. The Stakeholder Review Group Summary also reflects input obtained from stakeholders (comprised of professional and community organizations) following their review of a prior draft of the Guideline. Finally, the Peer Review Summary reflects input obtained from three scientific peer reviewers following their review of a draft of the full Guideline, along with a summary of comments received and CDC responses.
http://www.regulations.gov/#!documentDetail;D=CDC-2015-0112-0001
Background
CDC developed the draft Guideline to provide recommendations about opioid prescribing for primary care providers who are treating adult patients with chronic pain in outpatient settings, outside of active cancer treatment, palliative care, and end-of-life care. The draft Guideline summarizes scientific knowledge about the effectiveness and risks of long-term opioid therapy, and provides recommendations for when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use. The draft Guideline identifies important gaps in the literature where further research is needed.
To develop the recommendations, CDC conducted a systematic review on benefits and harms of opioids and developed the draft Guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. CDC drafted recommendations and consulted with experts on the evidence to inform the recommendations. CDC hosted webinars in September 2015 and also provided opportunities for stakeholder and peer review of the draft Guideline. The Guideline is not a federal regulation; adherence to the Guideline will be voluntary. For additional information on prescription drug overdose, please visit http://www.cdc.gov/drugoverdose/prescribing/guideline.html.
Supporting and Related Material in the Docket
The docket contains the following supporting and related materials to help inform public comment: The Guideline; the Clinical Evidence Review Appendix; the Contextual Evidence Review Appendix; and three documents that comprise the Comment Summaries and CDC Responses (Constituent Comment Summary, Peer Review Summary, and Stakeholder Review Group Summary). The Clinical Evidence Review Appendix and the Contextual Evidence Review Appendix include primary evidence, studies, and data tables that were used by CDC to develop the recommendations in the Guideline. The Constituent Comment Summary reflects input obtained in response to webinars hosted on September 16 and September 17, 2015, during which CDC shared an overview of the development process and draft recommendation statements. The Stakeholder Review Group Summary also reflects input obtained from stakeholders (comprised of professional and community organizations) following their review of a prior draft of the Guideline. Finally, the Peer Review Summary reflects input obtained from three scientific peer reviewers following their review of a draft of the full Guideline, along with a summary of comments received and CDC responses.
http://www.regulations.gov/#!documentDetail;D=CDC-2015-0112-0001
NYTimes: Where Is the Cure for the Migraine?
At least 36 million Americans suffer from migraines, and while more and more medical professionals are on the case, they have never found satisfactory answers for why the pain starts, let alone how to make it end.
Lately, it seems I can't attend a gathering of friends without at least one complaining about headaches, and another offering advice: It's your glasses, your diet or, the old standby, your stress level. Regarding the latter, let me say that a friend and I once spent four days at a spa, doing nothing but exercise classes and beauty treatments, and we were still popping pills for our pounding heads nonstop.
Over the last few decades, migraines (intensely painful headaches that make it difficult to function and are often accompanied by other symptoms like vomiting) have become big business. Billions of dollars are spent annually on over-the-counter and prescription remedies, as well as visits to the increasing number of specialized clinics and hospital departments around the country. Even dermatologists, dentists and non-Western holistic practitioners are getting in on the action.
More ...
http://www.nytimes.com/2015/12/13/opinion/sunday/where-is-the-cure-for-the-migraine.html?
Lately, it seems I can't attend a gathering of friends without at least one complaining about headaches, and another offering advice: It's your glasses, your diet or, the old standby, your stress level. Regarding the latter, let me say that a friend and I once spent four days at a spa, doing nothing but exercise classes and beauty treatments, and we were still popping pills for our pounding heads nonstop.
Over the last few decades, migraines (intensely painful headaches that make it difficult to function and are often accompanied by other symptoms like vomiting) have become big business. Billions of dollars are spent annually on over-the-counter and prescription remedies, as well as visits to the increasing number of specialized clinics and hospital departments around the country. Even dermatologists, dentists and non-Western holistic practitioners are getting in on the action.
More ...
http://www.nytimes.com/2015/12/13/opinion/sunday/where-is-the-cure-for-the-migraine.html?
Woman who has never felt pain experiences it for the first time | New Scientist
A woman born incapable of feeling pain has been hurt for the first time – thanks to a drug normally prescribed for opioid overdoses. She was burned with a laser, and quite liked the experience.
The breakthrough may lead to powerful new ways to treat painful conditions such as arthritis.
Only a handful people around the world are born unable to feel pain. These individuals can often suffer a range of injuries when they are young. Babies with the condition tend to chew their fingers, toes and lips until they bleed, and toddlers can suffer an increased range of knocks, tumbles and encounters with sharp or hot objects.
The disorder is caused by a rare genetic mutation that results in a lack of ion channels that transport sodium across sensory nerves. Without these channels, known as Nav1.7 channels, nerve cells are unable to communicate pain. Researchers quickly sought to make compounds that blocked Nav1.7 channels, thinking they might be able to block pain in people without the disorder.
"It looked like a fantastic drug target," says John Wood at University College London. "Pharma companies went bananas and made lots of drugs." But while a few compounds saw some success, none brought about the total pain loss seen in people who lack the channel naturally.
To find out why, Wood and his colleagues studied mice that had been genetically modified to lack Nav1.7. These animals don't feel pain, either – they show no reaction when their tails are exposed to extreme hot or cold temperatures, for example.
A closer analysis of the rodents' nerves showed that mice lacking Nav1.7 had a huge increase in the expression of genes responsible for opioid peptides, the body's natural painkiller. The mice seem to be making more of these pain-relieving peptides, which might explain why people lacking the channel don't feel pain, either.
More ...
https://www.newscientist.com/article/dn28623-woman-who-has-never-felt-pain-experiences-it-for-the-first-time/?
The breakthrough may lead to powerful new ways to treat painful conditions such as arthritis.
Only a handful people around the world are born unable to feel pain. These individuals can often suffer a range of injuries when they are young. Babies with the condition tend to chew their fingers, toes and lips until they bleed, and toddlers can suffer an increased range of knocks, tumbles and encounters with sharp or hot objects.
The disorder is caused by a rare genetic mutation that results in a lack of ion channels that transport sodium across sensory nerves. Without these channels, known as Nav1.7 channels, nerve cells are unable to communicate pain. Researchers quickly sought to make compounds that blocked Nav1.7 channels, thinking they might be able to block pain in people without the disorder.
"It looked like a fantastic drug target," says John Wood at University College London. "Pharma companies went bananas and made lots of drugs." But while a few compounds saw some success, none brought about the total pain loss seen in people who lack the channel naturally.
To find out why, Wood and his colleagues studied mice that had been genetically modified to lack Nav1.7. These animals don't feel pain, either – they show no reaction when their tails are exposed to extreme hot or cold temperatures, for example.
A closer analysis of the rodents' nerves showed that mice lacking Nav1.7 had a huge increase in the expression of genes responsible for opioid peptides, the body's natural painkiller. The mice seem to be making more of these pain-relieving peptides, which might explain why people lacking the channel don't feel pain, either.
More ...
https://www.newscientist.com/article/dn28623-woman-who-has-never-felt-pain-experiences-it-for-the-first-time/?
The end of migraines is close: A new drug could stop debilitating headaches before they start - Salon.com
The 63-year-old chief executive couldn't do his job. He had been crippled by migraine headaches throughout his adult life and was in the middle of a new string of attacks. "I have but a little moment in the morning in which I can either read, write or think," he wrote to a friend. After that, he had to shut himself up in a dark room until night. So President Thomas Jefferson, in the early spring of 1807, during his second term in office, was incapacitated every afternoon by the most common neurological disability in the world.
The co-author of the Declaration of Independence never vanquished what he called his "periodical head-ach," although his attacks appear to have lessened after 1808. Two centuries later 36 million American migraine sufferers grapple with the pain the president felt. Like Jefferson, who often treated himself with a concoction brewed from tree bark that contained quinine, they try different therapies, ranging from heart drugs to yoga to herbal remedies. Their quest goes on because modern medicine, repeatedly baffled in attempts to find the cause of migraine, has struggled to provide reliable relief.
Now a new chapter in the long and often curious history of migraine is being written. Neurologists believe they have identified a hypersensitive nerve system that triggers the pain and are in the final stages of testing medicines that soothe its overly active cells. These are the first ever drugs specifically designed to prevent the crippling headaches before they start, and they could be approved by the U.S. Food and Drug Administration next year. If they deliver on the promise they have shown in studies conducted so far, which have involved around 1,300 patients, millions of headaches may never happen.
"It completely changes the paradigm of how we treat migraine," says David Dodick, a neurologist at the Mayo Clinic's campus in Arizona and president of the International Headache Society. Whereas there are migraine-specific drugs that do a good job stopping attacks after they start, the holy grail for both patients and doctors has been prevention.
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http://www.salon.com/2015/11/29/the_end_of_migraines_could_be_close_partner/
The co-author of the Declaration of Independence never vanquished what he called his "periodical head-ach," although his attacks appear to have lessened after 1808. Two centuries later 36 million American migraine sufferers grapple with the pain the president felt. Like Jefferson, who often treated himself with a concoction brewed from tree bark that contained quinine, they try different therapies, ranging from heart drugs to yoga to herbal remedies. Their quest goes on because modern medicine, repeatedly baffled in attempts to find the cause of migraine, has struggled to provide reliable relief.
Now a new chapter in the long and often curious history of migraine is being written. Neurologists believe they have identified a hypersensitive nerve system that triggers the pain and are in the final stages of testing medicines that soothe its overly active cells. These are the first ever drugs specifically designed to prevent the crippling headaches before they start, and they could be approved by the U.S. Food and Drug Administration next year. If they deliver on the promise they have shown in studies conducted so far, which have involved around 1,300 patients, millions of headaches may never happen.
"It completely changes the paradigm of how we treat migraine," says David Dodick, a neurologist at the Mayo Clinic's campus in Arizona and president of the International Headache Society. Whereas there are migraine-specific drugs that do a good job stopping attacks after they start, the holy grail for both patients and doctors has been prevention.
More ...
http://www.salon.com/2015/11/29/the_end_of_migraines_could_be_close_partner/
'War on drugs means millions are dying in pain' - CNN.com
Ruth Dreifuss is former President of Switzerland and Minister of Home Affairs. Anand Grover is former U.N. special rapporteur on the Right to Health, India. Michel Kazatchkine is former executive director of the Global Fund to fight AIDS, Tuberculosis and Malaria. The opinions expressed in this commentary are theirs.
Millions of people are dying in pain because of the repressive stance the world has taken on drugs. That's because states are obsessed by the fear that people will use controlled medicines such as morphine as recreational drugs, thereby neglecting their important medical uses.
Where you live determines whether you will be able to access to controlled medicines, particularly opiates, when confronting an acute terminal, chronic or painful illness. Ninety-two per cent of the world's morphine is consumed by only 17% of the world's population, primarily the United States and Europe. Seventy--five percent of the world's people in need do not have access to pain relieving medicine.
In other words, most of the global population, outside the affluent countries in the North, dying in pain, including from terminal cancers, do so in the absence of dignified palliative care.
This is a horrendous situation for millions of patients and families. Essential medicines such as morphine, taken for granted as the standard relief of severe pain in the global North, do not enjoy the same status in the global South. Quite the opposite. Chances are, if a person living in any developing country ends up with an illness associated with extreme and avoidable pain, they will endure the pain simply because their government has created obstacles to morphine use in hospitals.
More ...
http://www.cnn.com/2015/11/17/opinions/controlled-medicines-access-gcdp/
Millions of people are dying in pain because of the repressive stance the world has taken on drugs. That's because states are obsessed by the fear that people will use controlled medicines such as morphine as recreational drugs, thereby neglecting their important medical uses.
Where you live determines whether you will be able to access to controlled medicines, particularly opiates, when confronting an acute terminal, chronic or painful illness. Ninety-two per cent of the world's morphine is consumed by only 17% of the world's population, primarily the United States and Europe. Seventy--five percent of the world's people in need do not have access to pain relieving medicine.
In other words, most of the global population, outside the affluent countries in the North, dying in pain, including from terminal cancers, do so in the absence of dignified palliative care.
This is a horrendous situation for millions of patients and families. Essential medicines such as morphine, taken for granted as the standard relief of severe pain in the global North, do not enjoy the same status in the global South. Quite the opposite. Chances are, if a person living in any developing country ends up with an illness associated with extreme and avoidable pain, they will endure the pain simply because their government has created obstacles to morphine use in hospitals.
More ...
http://www.cnn.com/2015/11/17/opinions/controlled-medicines-access-gcdp/
CDC assists in heroin, fentanyl investigation in Greater Cincinnati | Local News - WLWT Home
Cincinnati - The heroin problem in Ohio is now getting attention from the Centers for Disease Control and Prevention.
The federal agency has been asked to come here and help find answers to a disturbing new trend that is costing lives – heroin mixed with a prescription pain medication.
State and local health experts said they are hoping what they learn during meetings Tuesday at the Hamilton County Board of Health will help them tackle the heroin crisis.
The CDC has a six-person team on the ground in Ohio, meeting with the Ohio Department of Health, and the Hamilton County Health Department.
Officials said they're focusing on a particular part of the heroin crisis – the number of deaths related to fentanyl.
Authorities said fentanyl is a prescription pain medication that has been showing up in heroin. The big mystery is why it's being mixed with heroin.
"We don't fully understand the fentanyl situation, and that's one of the reasons we wanted their help with this," said Dr. Mary DiOrio, the medical director of the Ohio Department of Health.
ODH asked the CDC to help look into the problem.
"We think that some people don't even know that it's in what they're injecting so we're trying to fully understand what people do and don't know so we can target the messages appropriately so we can protect lives," DiOrio said.
We've seen the deadly consequences of fentanyl in Greater Cincinnati.
Kenneth Gentry is facing charges in the overdose death of an Arlington Heights man earlier this year that was blamed on fentanyl.
Authorities said the fentanyl problem causes only a fraction of the deaths heroin alone causes – but it's a problem that's growing quickly.
Authorities said heroin deaths increased 18 percent in Ohio last year to a total of nearly 2,500. In 2014 there were about 500 deaths linked to fentanyl – an increase of nearly 600 percent from the year before.
More ...
http://www.wlwt.com/news/cdc-assists-in-heroin-fentanyl-investigation-in-greater-cincinnati/
The federal agency has been asked to come here and help find answers to a disturbing new trend that is costing lives – heroin mixed with a prescription pain medication.
State and local health experts said they are hoping what they learn during meetings Tuesday at the Hamilton County Board of Health will help them tackle the heroin crisis.
The CDC has a six-person team on the ground in Ohio, meeting with the Ohio Department of Health, and the Hamilton County Health Department.
Officials said they're focusing on a particular part of the heroin crisis – the number of deaths related to fentanyl.
Authorities said fentanyl is a prescription pain medication that has been showing up in heroin. The big mystery is why it's being mixed with heroin.
"We don't fully understand the fentanyl situation, and that's one of the reasons we wanted their help with this," said Dr. Mary DiOrio, the medical director of the Ohio Department of Health.
ODH asked the CDC to help look into the problem.
"We think that some people don't even know that it's in what they're injecting so we're trying to fully understand what people do and don't know so we can target the messages appropriately so we can protect lives," DiOrio said.
We've seen the deadly consequences of fentanyl in Greater Cincinnati.
Kenneth Gentry is facing charges in the overdose death of an Arlington Heights man earlier this year that was blamed on fentanyl.
Authorities said the fentanyl problem causes only a fraction of the deaths heroin alone causes – but it's a problem that's growing quickly.
Authorities said heroin deaths increased 18 percent in Ohio last year to a total of nearly 2,500. In 2014 there were about 500 deaths linked to fentanyl – an increase of nearly 600 percent from the year before.
More ...
http://www.wlwt.com/news/cdc-assists-in-heroin-fentanyl-investigation-in-greater-cincinnati/
How Doctors Helped Drive the Addiction Crisis - The New York Times
There has been an alarming and steady increase in the mortality rate of middle-aged white Americans since 1999, according to a study published last week. This increase — half a percent annually — contrasts starkly with decreasing death rates in all other age and ethnic groups and with middle-aged people in other developed countries.
So what is killing middle-aged white Americans? Much of the excess death is attributable to suicide and drug and alcohol poisonings. Opioid painkillers like OxyContin prescribed by physicians contribute significantly to these drug overdoses.
Thus, it seems that an opioid overdose epidemic is at the heart of this rise in white middle-age mortality. The rate of death from prescription opioids in the United States increased more than fourfold between 1999 and 2010, dwarfing the combined mortality from heroin and cocaine. In 2013 alone, opioids were involved in 37 percent of all fatal drug overdoses.
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http://www.nytimes.com/2015/11/08/opinion/sunday/how-doctors-helped-drive-the-addiction-crisis.html?r
So what is killing middle-aged white Americans? Much of the excess death is attributable to suicide and drug and alcohol poisonings. Opioid painkillers like OxyContin prescribed by physicians contribute significantly to these drug overdoses.
Thus, it seems that an opioid overdose epidemic is at the heart of this rise in white middle-age mortality. The rate of death from prescription opioids in the United States increased more than fourfold between 1999 and 2010, dwarfing the combined mortality from heroin and cocaine. In 2013 alone, opioids were involved in 37 percent of all fatal drug overdoses.
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http://www.nytimes.com/2015/11/08/opinion/sunday/how-doctors-helped-drive-the-addiction-crisis.html?r
Phantom pain: It feels real even though it’s all in the brain - The Washington Post
Several years ago, Peggy Chenoweth began having excruciating cramping in her ankle. It felt severely sprained and as if her toe were twisting to the point where it was being ripped off her foot.
"The pain is right here," she told an orthopedic surgeon, "in my ankle and foot." But the 41-year-old Gainesville, Va., resident no longer had that ankle and foot. Her leg had been amputated below the knee after a large piece of computer equipment fell off a cart, crushed her foot and caused nerve damage. Further, she insisted that since the amputation, she could feel her missing toes move.
Chenoweth's surgeon knew exactly what was going on: phantom pain.
Lynn Webster, an anesthesiologist and past president of the American Academy of Pain Medicine, explains the phenomenon: "With 'phantom pain,' nerves that transmitted information from the brain to the now-missing body part continue to send impulses, which relay the message of pain."
It feels as if the removed part is still there and hurting, but pain is actually in the brain. The sensation ranges from annoying itching to red-hot burning.
Physicians wrote about phantom pain as early as the 1860s, but U.S. research on this condition has increased recently, spurred by the surge of amputees returning from warfare in Iraq and Afghanistan and by increasing rates of diabetes. (Since 2003, nearly 1,650 service members have lost limbs, according to the Congressional Research Service. In 2010, about 73,000 amputations were performed on diabetics in the United States, according to the Centers for Disease Control and Prevention.)
More ...
https://www.washingtonpost.com/national/health-science/phantom-pain-it-feels-real-even-though-its-all-in-the-brain/2015/11/09/a32830a8-3fa3-11e5-8d45-d815146f81fa_story.html?
"The pain is right here," she told an orthopedic surgeon, "in my ankle and foot." But the 41-year-old Gainesville, Va., resident no longer had that ankle and foot. Her leg had been amputated below the knee after a large piece of computer equipment fell off a cart, crushed her foot and caused nerve damage. Further, she insisted that since the amputation, she could feel her missing toes move.
Chenoweth's surgeon knew exactly what was going on: phantom pain.
Lynn Webster, an anesthesiologist and past president of the American Academy of Pain Medicine, explains the phenomenon: "With 'phantom pain,' nerves that transmitted information from the brain to the now-missing body part continue to send impulses, which relay the message of pain."
It feels as if the removed part is still there and hurting, but pain is actually in the brain. The sensation ranges from annoying itching to red-hot burning.
Physicians wrote about phantom pain as early as the 1860s, but U.S. research on this condition has increased recently, spurred by the surge of amputees returning from warfare in Iraq and Afghanistan and by increasing rates of diabetes. (Since 2003, nearly 1,650 service members have lost limbs, according to the Congressional Research Service. In 2010, about 73,000 amputations were performed on diabetics in the United States, according to the Centers for Disease Control and Prevention.)
More ...
https://www.washingtonpost.com/national/health-science/phantom-pain-it-feels-real-even-though-its-all-in-the-brain/2015/11/09/a32830a8-3fa3-11e5-8d45-d815146f81fa_story.html?
Gimlet Media | Podcast #42 Blind Spot
SRUTHI: Okay. So this is a story about a woman whose body started breaking down in increasingly weird ways. It's as if her body turns into a David Lynch movie, and there's nothing she can do to understand it, and nothing she can do to convince people it's real. For the purposes of the story, we will call this woman "Hope." And it all starts last year. Hope is 29, living in the suburbs of Pittsburgh. And one beautiful winter morning…
HOPE: I was walking at a soccer field that's near my house when I first noticed, "Well that feels weird, my eye feels such a weird nagging eye pressure. Almost like my eye was bulging a little bit, from the inside out.
SRUTHI: It's so bad that she feels as if people can see it, like it's bulging so much, this one eye.
PJ: Can she, like if she stands in front of the bathroom mirror and stares at her face, can she feel like she can see her eye bulging?
SRUTHI: No. So it goes on for a couple of weeks, doesn't go away. And then she says you know what, I'm just gonna have this looked at.
HOPE: I actually just went to the eye doctor that's in Walmart, and she looked at my eye, and she didn't find anything at all wrong with the eye. The eye was perfectly healthy and normal.
SRUTHI: This bulging feeling, it goes on for a whole month. And then one day, she wakes up and it's gone.
HOPE: This would, be I should say this, this would be something in my life that I would probably never give a second thought to, this mild eye problem that I had for a month, if… what happened next hadn't happened.
SRUTHI: It's evening. Hope is working. She's a wedding photographer, and she's setting up room in her house where she can meet clients.
HOPE: And all of the sudden I stood up, and I couldn't see out of my right eye. I thought, "Oh my gosh, am I having a stroke?" I had field of vision in like three-quarters of the eye, but the one quarter was completely covered by this weird zigzag freaky thing. It's almost like a kaleidoscope when you were a kid, and you used to hold up a kaleidoscope to your eye and it would… it would like shine and shimmer, like a piece of mirrored paper in there. So I actually remember waking up my sister, and she said "what are you talking about?" and I said "I can't see out of my eye, I'm freaking out."
More ...
At first, this man thought he had food poisoning. It turned out to be something far worse. - The Washington Post
Jeffrey Sank always knew when he was going to have an attack: Its onset was signaled by the same kind of uneasy, "uh-oh" feeling that portends an impending cold.
But Sank's problem wasn't in his head — it was in his gut. And when he felt the initial abdominal pangs, he knew that he had about 12 hours before he was miserable, or at worst incapacitated, for the next day or two.
"It almost felt like I'd done 1,000 sit-ups or been punched in the gut 100 times," said the digital media specialist, 43, who lives in the District. At first the attacks were intermittent. But after several months the pain, centered in the right upper quadrant where the liver and gallbladder are located, increased in severity and frequency.
For nearly a year, Sank, with the help of his stepmother, a physician, struggled to determine the reason for his pain. He saw multiple doctors, including two gastroenterologists, a kidney specialist and an infectious-disease physician. He underwent workups for reflux disease, a liver disorder, an intestinal blockage and malaria. One doctor suspected he might be faking.
Sank's problem turned out to be none of those things. His diagnosis was partly the result of serendipity: The second gastroenterologist he consulted was familiar with the malady, which is common in other parts of the world but not the United States. To complicate matters, Sank's case did not fit the standard diagnostic criteria.
"It's in the differential [a list of possible disorders suggested by symptoms], but since we never really see it, you don't necessarily think of it," said Montgomery County gastroenterologist William Steinberg. Luckily, something Steinberg had seen two decades earlier on a medical trip to the Middle East resonated when an increasingly desperate Sank consulted him in April 2010.
The first time he suffered stomach pain in June 2009, Sank assumed he had food poisoning. "I really didn't think much about it," he recalled.
When it kept recurring, he consulted his stepmother, Catherine Shaer, a retired pediatrician, for advice. Sank was otherwise healthy, and Shaer agreed that he should see a gastroenterologist.
At his initial appointment in October 2009, the gastroenterologist told Sank he suspected his pain was the result of gallstonesand ordered a sonogram.
The test was memorable: Sank said that during the procedure the technician began acting strangely and then summoned a radiologist. In a somber voice, Sank recalled, the radiologist "told me that there was a huge lesion on my liver and they were going to send me immediately for a CT scan."
The radiologist then told him, Sank recalled, "there was something very serious going on here and that I needed to prepare myself and my family for what I had to deal with." Sank also remembers the specialist saying that his "door was always open."
"I thought I had liver cancer and was going to die," Sank remembered. At the time, his first child was only a few months old.
While waiting for the CT scan, Sank telephoned his stepmother and a friend who is an oncologist. Both told him that they were sure that the growth on his liver, the size of a large strawberry, would turn out to be a benign hemangioma. He had no cancer symptoms, and such tumors are common. A few hours later, Sank, hugely relieved, learned they were right. He didn't have cancer. Nor did he have gallstones. "We were back to square one," he recalled.
More ...
https://www.washingtonpost.com/national/health-science/at-first-a-man-thought-he-had-food-poisoning-not-so/2015/10/26/71290448-4e61-11e5-902f-39e9219e574b_story.html?
But Sank's problem wasn't in his head — it was in his gut. And when he felt the initial abdominal pangs, he knew that he had about 12 hours before he was miserable, or at worst incapacitated, for the next day or two.
"It almost felt like I'd done 1,000 sit-ups or been punched in the gut 100 times," said the digital media specialist, 43, who lives in the District. At first the attacks were intermittent. But after several months the pain, centered in the right upper quadrant where the liver and gallbladder are located, increased in severity and frequency.
For nearly a year, Sank, with the help of his stepmother, a physician, struggled to determine the reason for his pain. He saw multiple doctors, including two gastroenterologists, a kidney specialist and an infectious-disease physician. He underwent workups for reflux disease, a liver disorder, an intestinal blockage and malaria. One doctor suspected he might be faking.
Sank's problem turned out to be none of those things. His diagnosis was partly the result of serendipity: The second gastroenterologist he consulted was familiar with the malady, which is common in other parts of the world but not the United States. To complicate matters, Sank's case did not fit the standard diagnostic criteria.
"It's in the differential [a list of possible disorders suggested by symptoms], but since we never really see it, you don't necessarily think of it," said Montgomery County gastroenterologist William Steinberg. Luckily, something Steinberg had seen two decades earlier on a medical trip to the Middle East resonated when an increasingly desperate Sank consulted him in April 2010.
The first time he suffered stomach pain in June 2009, Sank assumed he had food poisoning. "I really didn't think much about it," he recalled.
When it kept recurring, he consulted his stepmother, Catherine Shaer, a retired pediatrician, for advice. Sank was otherwise healthy, and Shaer agreed that he should see a gastroenterologist.
At his initial appointment in October 2009, the gastroenterologist told Sank he suspected his pain was the result of gallstonesand ordered a sonogram.
The test was memorable: Sank said that during the procedure the technician began acting strangely and then summoned a radiologist. In a somber voice, Sank recalled, the radiologist "told me that there was a huge lesion on my liver and they were going to send me immediately for a CT scan."
The radiologist then told him, Sank recalled, "there was something very serious going on here and that I needed to prepare myself and my family for what I had to deal with." Sank also remembers the specialist saying that his "door was always open."
"I thought I had liver cancer and was going to die," Sank remembered. At the time, his first child was only a few months old.
While waiting for the CT scan, Sank telephoned his stepmother and a friend who is an oncologist. Both told him that they were sure that the growth on his liver, the size of a large strawberry, would turn out to be a benign hemangioma. He had no cancer symptoms, and such tumors are common. A few hours later, Sank, hugely relieved, learned they were right. He didn't have cancer. Nor did he have gallstones. "We were back to square one," he recalled.
More ...
https://www.washingtonpost.com/national/health-science/at-first-a-man-thought-he-had-food-poisoning-not-so/2015/10/26/71290448-4e61-11e5-902f-39e9219e574b_story.html?
PA-14-244: Research on Chronic Overlapping Pain Conditions (R01)
Chronic pain affects approximately 100 million Americans and exacts large economic, social and personal costs. It is a major public health challenge that needs to be addressed at multiple levels including the generation of new scientific knowledge that will enhance our understanding of these conditions. Current research efforts in chronic pain conditions have focused on single disorders or types of pain such as neuropathic and inflammatory pain. These research efforts have generated a substantial body of information advancing our discovery and understanding of the underlying mechanisms of pain onset and development, the transition from acute to chronic pain, and promising therapeutic targets for treating acute and chronic pain. Over the past twenty years sporadic reports have documented the presence of more than one chronic pain condition in subjects with pain. Studies have identified overlap between a number of chronic pain conditions, including temporomandibular joint disorder (TMD), fibromyalgia (FM), vulvodynia, functional gastrointestinal disorders such as irritable bowel syndrome (IBS), migraine, and urologic chronic pelvic pain syndromes (UCPPS). These results suggest that chronic pain conditions may not be localized conditions, but may share symptoms and mechanisms that involve a general central nervous system dysfunction as well as disorder-specific symptoms. More recent evidence is supportive of the idea that chronic pain conditions are complex disorders consistent with a biopsychosocial model of pain, and exhibit substantial overlap. Therefore, this may be an opportune time to encourage research efforts that focus, not on single pain conditions, but on subjects with multiple chronic pain disorders.
Chronic pain conditions represent a complex set of painful disorders that lack a firm mechanistic understanding, and are in need of hypothesis-driven research efforts. A new focus on overlapping pain conditions is warranted to develop therapies to prevent and treat these overlapping disorders and to develop approaches to better manage pain that can be disabling. A workshop sponsored by the NIH Pain Consortium was held in the summer of 2012 titled "A Workshop on Chronic Overlapping Pain Conditions". It brought together researchers with expertise in various pain conditions and other relevant expertise to discuss these conditions and to develop a forward-thinking research agenda. The workshop focused on our current understanding of chronic overlapping pain conditions, their etiology, risk factors, mechanisms of disease, outcome measures, and diagnosis. Topics of discussion included epidemiology of chronic overlapping pain conditions, risk factors and mechanisms of disease, leveraging of current data sets, and new scientific approaches incorporating systems biology. The recommendations derived from this workshop have, in part, informed the development of this FOA.
Some of the overlapping pain conditions under consideration include, but are not limited to: chronic headache, migraine headache, temporomandibular joint disorder, generalized pain conditions, functional gastrointestinal disorders such as irritable bowel syndrome, endometriosis, urologic chronic pelvic pain, vulvodynia, fibromyalgia, chronic fatigue syndrome and osteoarthritis.
More ...IPRP Ontology | Interagency Pain Research Portfolio -The Federal Government's Pain Research Database
The grants in the Federal pain research portfolio were classified using a multi-tiered system. In Tier 1, grants were designated as basic, translational, or clinical. Grants then were coded into 29 scientific topic categories (Tier 2). Following this classification, the Tier 2 categories were organized into 9 overarching themes based on similarity of topic.
http://paindatabase.nih.gov/content/iprp-ontology
http://paindatabase.nih.gov/content/iprp-ontology
The Interagency Pain Research Coordinating Committee (IPRCC)
The Patient Protection and Affordable Care Act (PPACA) includes a number of provisions designed to advance pain research, care, and education, including the creation of the Interagency Pain Research Coordinating Committee (IPRCC) by the Department of Health and Human Services (HHS). On behalf of HHS, the NIH established the IPRCC to coordinate all pain research efforts within HHS and across other Federal Agencies. The Committee is composed of seven Federal members and twelve non-Federal members, six drawn from the scientific and medical communities and six members of the public and stakeholder groups. The Department of Health and Human Services Secretary will review the necessity of the Committee at least once every 2 years.
As specified in Section 4305(b) of the Public Law 111-148 ("Affordable Care Act (ACA)") the Committee has been asked to:
- Develop a summary of advances in pain care research supported or conducted by the Federal agencies relevant to the diagnosis, prevention, and treatment of pain and diseases and disorders associated with pain
- Identify critical gaps in basic and clinical research on the symptoms and causes of pain
- Make recommendations to ensure that the activities of the National Institutes of Health and other Federal agencies are free of unnecessary duplication of effort
- Make recommendations on how best to disseminate information on pain care
- Make recommendations on how to expand partnerships between public entities and private entities to expand collaborative, cross-cutting research
How Doctors Take Women's Pain Less Seriously - The Atlantic
Early on a Wednesday morning, I heard an anguished cry—then silence.
I rushed into the bedroom and watched my wife, Rachel, stumble from the bathroom, doubled over, hugging herself in pain.
"Something's wrong," she gasped.
This scared me. Rachel's not the type to sound the alarm over every pinch or twinge. She cut her finger badly once, when we lived in Iowa City, and joked all the way to Mercy Hospital as the rag wrapped around the wound reddened with her blood. Once, hobbled by a training injury in the days before a marathon, she limped across the finish line anyway.
So when I saw Rachel collapse on our bed, her hands grasping and ungrasping like an infant's, I called the ambulance. I gave the dispatcher our address, then helped my wife to the bathroom to vomit.
I don't know how long it took for the ambulance to reach us that Wednesday morning. Pain and panic have a way of distorting time, ballooning it, then compressing it again. But when we heard the sirens wailing somewhere far away, my whole body flooded with relief.
I didn't know our wait was just beginning.
I buzzed the EMTs into our apartment. We answered their questions: When did the pain start? That morning. Where was it on a scale of one to 10, with 10 being worst?
"Eleven," Rachel croaked.
As we loaded into the ambulance, here's what we didn't know: Rachel had an ovarian cyst, a fairly common thing. But it had grown, undetected, until it was so large that it finally weighed her ovary down, twisting the fallopian tube like you'd wring out a sponge. This is called ovarian torsion, and it creates the kind of organ-failure pain few people experience and live to tell about.
"Ovarian torsion represents a true surgical emergency," says an article in the medical journal Case Reports in Emergency Medicine. "High clinical suspicion is important. … Ramifications include ovarian loss, intra-abdominal infection, sepsis, and even death." The best chance of salvaging a torsed ovary is surgery within eight hours of when the pain starts.
There is nothing like witnessing a loved one in deadly agony. Your muscles swell with the blood they need to fight or run. I felt like I could bend iron, tear nylon, through the 10-minute ambulance ride and as we entered the windowless basement hallways of the hospital.
And there we stopped. The intake line was long—a row of cots stretched down the darkened hall. Someone wheeled a gurney out for Rachel. Shaking, she got herself between the sheets, lay down, and officially became a patient.
More ...
http://www.theatlantic.com/health/archive/2015/10/emergency-room-wait-times-sexism/410515/?
I rushed into the bedroom and watched my wife, Rachel, stumble from the bathroom, doubled over, hugging herself in pain.
"Something's wrong," she gasped.
This scared me. Rachel's not the type to sound the alarm over every pinch or twinge. She cut her finger badly once, when we lived in Iowa City, and joked all the way to Mercy Hospital as the rag wrapped around the wound reddened with her blood. Once, hobbled by a training injury in the days before a marathon, she limped across the finish line anyway.
So when I saw Rachel collapse on our bed, her hands grasping and ungrasping like an infant's, I called the ambulance. I gave the dispatcher our address, then helped my wife to the bathroom to vomit.
I don't know how long it took for the ambulance to reach us that Wednesday morning. Pain and panic have a way of distorting time, ballooning it, then compressing it again. But when we heard the sirens wailing somewhere far away, my whole body flooded with relief.
I didn't know our wait was just beginning.
I buzzed the EMTs into our apartment. We answered their questions: When did the pain start? That morning. Where was it on a scale of one to 10, with 10 being worst?
"Eleven," Rachel croaked.
As we loaded into the ambulance, here's what we didn't know: Rachel had an ovarian cyst, a fairly common thing. But it had grown, undetected, until it was so large that it finally weighed her ovary down, twisting the fallopian tube like you'd wring out a sponge. This is called ovarian torsion, and it creates the kind of organ-failure pain few people experience and live to tell about.
"Ovarian torsion represents a true surgical emergency," says an article in the medical journal Case Reports in Emergency Medicine. "High clinical suspicion is important. … Ramifications include ovarian loss, intra-abdominal infection, sepsis, and even death." The best chance of salvaging a torsed ovary is surgery within eight hours of when the pain starts.
There is nothing like witnessing a loved one in deadly agony. Your muscles swell with the blood they need to fight or run. I felt like I could bend iron, tear nylon, through the 10-minute ambulance ride and as we entered the windowless basement hallways of the hospital.
And there we stopped. The intake line was long—a row of cots stretched down the darkened hall. Someone wheeled a gurney out for Rachel. Shaking, she got herself between the sheets, lay down, and officially became a patient.
More ...
http://www.theatlantic.com/health/archive/2015/10/emergency-room-wait-times-sexism/410515/?
Long-term Opioid Therapy Less Effective for Many Women | Psych Central News
A new study shows that women — especially younger women — are less likely than men to find relief from pain with long-term opioid use.
The new study, published in the Journal of Women's Health, found that only one in five women reported low levels of pain and high levels of function with chronic opioid therapy.
In the study, researchers led by Linda LeResche, Sc.D., of the Department of Oral Medicine at the University of Washington School of Dentistry in Seattle, evaluated pain status among chronic opioid therapy users.
The researchers report that young and middle-aged women are at particularly high risk for unfavorable global pain status.
Additionally, young and middle-aged women face "unique risks" from opioid use, such as reduced fertility and potential effects of opioids used during pregnancy on the developing fetus, the researchers reported.
"Given the high rates of chronic opioid use in women, along with evidence of poor relief from pain and concerning risks, particularly in reproductive-aged women, we need more effective and safer options for managing pain in this population," noted Susan G. Kornstein, M.D., editor-in-chief of the Journal of Women's Health, executive director of the Virginia Commonwealth University Institute for Women's Health in Richmond, Virginia, and president of the Academy of Women's Health.
Strong placebo response thwarts painkiller trials : Nature News
Most new painkiller drugs fail in clinical trials — but a growing placebo response may be to blame.
Drug companies have a problem: they are finding it ever harder to get painkillers through clinical trials. But this isn't necessarily because the drugs are getting worse. An extensive analysis of trial data1 has found that responses to sham treatments have become stronger over time, making it harder to prove a drug's advantage over placebo.
The change in reponse to placebo treatments for pain, discovered by researchers in Canada, holds true only for US clinical trials. "We were absolutely floored when we found out," says Jeffrey Mogil, who directs the pain-genetics lab at McGill University in Montreal and led the analysis. Simply being in a US trial and receiving sham treatment now seems to relieve pain almost as effectively as many promising new drugs. Mogil thinks that as US trials get longer, larger and more expensive, they may be enhancing participants' expectations of their effectiveness.
Stronger placebo responses have already been reported for trials of antidepressants and antipsychotics2, 3, triggering debate over whether growing placebo effects are seen in pain trials too. To find out, Mogil and his colleagues examined 84 clinical trials of drugs for the treatment of chronic neuropathic pain (pain which affects the nervous system) published between 1990 and 2013.
Based on patients' ratings of their pain, the effect of trialled drugs in relieving symptoms stayed the same over the 23-year period — but placebo responses rose. In 1996, patients in clinical trials reported that drugs relieved their pain by 27% more than did a placebo. But by 2013, that gap had slipped to just 9%. The phenomenon is driven by 35 US trials; among trials in Europe, Asia and elsewhere, there was no significant change in placebo reponses.The analysis is in press in the journal Pain1.
Only in America
This effect would explain why drug companies have trouble getting new painkillers through trials, notes neuroscientist Fabrizio Benedetti, who studies placebo responses at the University of Turin, Italy. Over the past ten years, he says, more than 90% of potential drugs for treatment of neuropathic and cancer pain have failed at advanced phases of clinical trials.
But the finding that placebo responses are rising only in the United States is the most surprising aspect of the latest analysis. One possible explanation is that direct-to-consumer advertising for drugs — allowed only in the United States and New Zealand — has increased people's expectations of the benefits of drugs, creating stronger placebo effects. But Mogil's results hint at another factor. "Our data suggest that the longer a trial is and the bigger a trial is, the bigger the placebo is going to be," he says.
Longer, bigger US trials probably cost more, and the glamour and gloss of their presentation might indirectly enhance patients' expectations, Mogil speculates. Some larger US trials also use contract research organizations that can employ nurses who are dedicated to the trial patients, he adds — giving patients a very different experience compared to those who take part in a small trial run by an academic lab, for instance, where research nurses may have many other responsibilities.
No pain, no gain?
Mogil's data also challenge one of the fundamental principles of placebo-controlled trials — that comparing a drug against placebo tells us how well a drug works. A basic principle of these trials is that drug and placebo effects are additive: our total response to any drug we take is equal to the placebo response plus the drug's biochemical effect. But Mogil found that although placebo responses have increased over time, drug responses haven't risen by the same amount.
That suggests placebo and drug responses may not always be strictly additive. This isn't entirely unexpected, Mogil argues, because both placebos and pharmaceutical painkillers tap into similar biological mechanisms — such as the release of endorphins in the brain. But if true, it suggests that growing placebo responses are masking real painkilling effects. "There are a lot of people in the pain field who believe the drugs that are failing clinical trials actually work, it's just that the trials can't show it," he says.
For companies trying to develop treatments, one remedy might be to compare new drugs against their best competitors instead of against placebo — or to go back to conducting smaller, shorter trials. Benedetti is not convinced, however. "I don't think that controlling the placebo response will increase the number of successful trials," he says. "What drug companies have to do is to find more effective drugs."
Mogil suggests it is also worth investigating the elements that generate the more powerful placebo response in US trials, and then incorporating those elements (such as the relationship between patient and nurse) into patient care. Ted Kaptchuk, director of placebo research at Harvard Medical School in Boston, Massachusetts, agrees. "If the major component of a drug in any particular condition is its placebo component, we need to develop non-pharmacological interventions as a first-line response," he says.
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