Monday, March 26, 2012

Lego sculpture - Nathan Sawaya

A man’s persistent headache proves hard to diagnose and harder to treat - The Washington Post

Driving south on the Baltimore-Washington Parkway bound for his Adams Morgan home in June 2009, Michael Herndon struggled to cope with the implications of what the doctor had just told him.

For months Herndon had tried to find out why the headache he developed on Nov. 15, 2008 — he remembered the exact date — had not gone away. The 41-year-old had consulted neurologists and ear, nose and throat specialists as well as an allergist and ophthalmologist, but none of them had figured out what was causing his pain.

"I was starting to hit a mental and physical wall," recalled Herndon, a consumer outreach specialist at the Commodity Futures Trading Commission. "I'd been chasing this for more than six months. No one could tell me what it was. I just remember thinking, 'How am I going to be able to function if it never goes away?' "

He had taken multiple courses of antibiotics and corticosteroids as well as over-the-counter pain relievers, and he had even undergone sinus surgery, all to no avail. Doctors had ruled out a brain tumor and other ailments but had no idea why his head, and increasingly his nose, still hurt.

A month later, Herndon learned the name of his disorder. It would be another year before he found effective help to cope with his chronic, and still largely inexplicable, head pain.

Now a neurologist at a major medical center in Baltimore told him his sinuses looked clear and suggested that the headache might never disappear. But he did not give Herndon a name for his condition or a remedy, suggesting only that he find a headache specialist in the Washington area.

Aftermath of a stress test

In October 2008, after experiencing chest pain, Herndon saw a cardiologist who ordered a variety of tests. During a stress test, which measures the heart's ability to respond to exercise, "my head felt like I'd had one and a half drinks," Herndon recalled. Testing revealed nothing amiss with his heart, and the lightheadedness gradually disappeared over the next few days, replaced almost immediately by something else: a dull ache in his upper forehead and between his eyes.

At first Herndon, who rarely got headaches, didn't think much about it. But after several days, when the pain failed to recede or respond to nonprescription painkillers, he saw his primary-care doctor, who referred him to a neurologist, who ordered various scans.

Herndon's brain looked normal, but a CT scan revealed a significant sinus infection — his first. Doctors prescribed antibiotics in an effort to knock it out, which would presumably eradicate the headache.

That course of antibiotics was the first of many rounds that failed to vanquish his headache; corticosteroids did nothing, either. After a few months his ENT recommended endoscopic sinus surgery to clean out and open his still-blocked sinuses, a procedure endorsed by a second specialist.

After the operation, which was performed in March 2009, Herndon was optimistic that his headache would finally disappear. But a few weeks later, he said, he had the sinking realization that "nothing felt any different."

When he told his surgeon, the doctor looked at him with "confusion and some concern," Herndon recalled. "He told me, 'It should be better.' "

The surgeon prescribed more antibiotics. Herndon also saw an allergist and an ophthalmologist, neither of whom found anything that would account for his pain. He decided to consult a new specialist in Baltimore, particularly because his nose and upper teeth had begun to hurt.

After the Baltimore doctor told him his sinuses weren't the problem, Herndon decided to regroup. He had lost 15 pounds and had missed a significant amount of work, which worried him despite the support of his supervisor. He flew to Tennessee to spend two weeks visiting his mother and pondering what to do next.

Diagnosis brings little relief

While in Knoxville, he consulted a neurologist who specializes in treating headaches. Armed with his medical records, Herndon recounted his history, and the specialist gave his malady a name: Herndon was suffering from a condition called new daily persistent headache, which sounded more like a description than a diagnosis. The doctor also had sobering news. "He told me that we're probably never going to cure this, but there are things we can do to try and help you feel a little bit better."

First described in 1986, new daily persistent headache remains one of the hardest types of headaches to treat. The diagnosis is made on the basis of symptoms and history, not specific lab tests, and after other causes of in­trac­table head pain, including chronic meningitis, a blood clot or an aneurysm, have been ruled out.

Unlike with migraines, the pain of daily headaches tends to affect both sides of the head; there is no aura or vomiting, nor does pain worsen with routine physical activity. Onset is typically sudden, and the disorder often affects those who do not have a history of headaches. Doctors say that patients can often pinpoint the day they developed a headache, unlike with other types, which tend to occur more gradually.

In an article published last year in the journal Headache, Baylor College neurologist Randolph W. Evans and a colleague report that the average age of onset is 35, the disorder is more common in women, and it is rare, affecting less than 1 percent of the population.

Even among neurologists the disorder is little-known. Patients often see "numerous physicians in different specialties, dentists, psychologists and chiropractors in a dizzying and depressing musical chairs of expensive misdiagnoses and sometimes potentially harmful treatments," the authors write. Common misdiagnoses include sinusitis, eye strain, chronic Lyme disease and temporomandibular joint disorder.

Small studies have found a link with prior infection, including the ubiquitous Epstein-Barr virus, but the cause is unknown. Antidepressants and anti-seizure drugs have not generally proven effective, nor have nutritional supplements, acupuncture, chiropractic ma­nipu­la­tion or yoga.

"It's very different than migraine," said neurologist Jessica X. Ailani, director of the headache center at MedStar Georgetown University Hospital, who has been treating Herndon since 2010. "Because the cause is so unclear, treatment ends up being pick and choose."

Through trial and error, Herndon found a regimen that has diminished his pain: He takes two antidepressants that have been found to quell nerve pain. Once a month when the pain worsens, he adds a common epilepsy drug used to treat chronic pain.

While there's no way to know for sure, doctors have told Herndon that the sinus infection, which was probably present during his stress test, might have triggered the headache. Whether his surgery helped or hurt is hard to say, Ailani said.

Herndon is grateful that none of his doctors suggested that his problem was psychological, although before his diagnosis he wasn't so sure. "I wondered whether I was going crazy," he said, after specialists failed to find an explanation during those first difficult months.

Sometimes, he says, he is able to forget he has had a headache for 31 / years. "It's like a light on a dimmer switch," Herndon said. "It never quite goes off."

Sunday, March 25, 2012

Five Crises in Pain Management Dr. John D. Loeser - Pain: Clinical Updates, IASP

I believe that there are five preeminent crises in pain management today: (1) the lack of evidence for the outcomes of most of the things providers do for patients, (2) the inadequate education of primary care providers about pain and how to treat it, (3) the largely unknown value of opioid treatment for patients with chronic nonmalignant pain, (4) funding for the providers of pain management, and (5) access to multidisciplinary care. All of these issues may loom larger in the United States than elsewhere, but they are not unique to this country. Yes, there are other issues, but these seem to me to be the most important.

Proving that what we do has favorable outcomes for patients is certainly paramount, but we need to balance population-based studies with what we know about individual variation in response to treatment and the associated risks. Furthermore, evidence-based medicine does not address the needs that patients have for diagnosis, prognosis, guidance, and sympathy that have always been, and should remain, part of the provision of health care.1 Tyranny of data must be tempered by clinical judgment. This problem is compounded by the recommendations of the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) that research for prospective new drugs should be targeted at diagnosis, yet the real focus should be on mechanisms of pain. Randomized clinical trials are not the only reliable source of information about treatment utility; they are rarely useful for the assessment of long-term effects, either good or bad. Observational studies do have something to offer. There is going to be tension between those who fund health care and would like to use population-based studies to determine what will be funded, and those who actually provide care to patients and recognize that almost no one is average. If we consider the individual's rights to be preeminent, how do we deny someone the chance to have a favorable response to a treatment that most people would not benefit from? Physicians have always placed their patients foremost. Who is going to fund research on the treatment outcomes that we advocate for, especially treatments that are not drug or device based? Since the mandate of the National Institutes of Health (NIH) is to reduce the burden of disease, and since chronic pain produces more disability than the sum of cancer, heart disease, AIDS, and stroke, should we not look to the NIH to fund more pain treatment outcome trials?2 How do we get clinicians to have their patients participate in large trials that are necessary to determine population-based outcomes? How do we get all providers to record outcomes of their patients for such studies? Large national databases have been established in some countries. All patients evaluated and treated in any rehabilitation program in Sweden (including pain programs) are entered into a national register with demographics, diagnoses, and outcomes. In Quebec, all patients coming to tertiary care pain clinics are also entered into a data-base with a minimal 6-month follow up. These records include a structured physical examination, patient-reported outcomes, past treatments, new treatments, medications, and demographics. In Norway, all prescriptions are entered into a national database, which is used for research on opioid and benzodiazepine use and abuse. One way to get such outcomes and demographic data is to make physician reimbursement dependent not just upon the receipt of an operative report or clinic note but also upon follow-up data 6 and 12 months after treatment. All patients should be part of such studies, not just a small number selected for a randomized controlled trial. Why should any health care system fund care that has no known benefit to the patients? For such widespread data collection, we need to have a standardized database for all clinical outcomes studies so that meaningful comparisons can be made.3 We will also have to establish criteria for applying a diagnosis that are not solely based upon the procedure that the physician wishes to perform.

There are woeful inadequacies in pain education for medical students and advanced trainees.4–10 This shortfall has been noted for many years, and it remains, at least in the United States, the major cause of poor pain treatment. In Europe, this problem has begun to be addressed. In Nordic countries (Sweden, Denmark, Finland, Norway and Iceland), doctors who have completed clinical specialty training can enroll in a pain course. The Danish government will not allow any Danish doctor to practice as a pain doctor without having completed this course. Portugal also has such a course with a similar curriculum.

All physicians who deal with clinical illnesses will be confronted with chronic pain patients. For this reason, no one should receive a medical degree without learning core knowledge about both acute and chronic pain, including cancer pain and nonmalignant pain. There are hospitals that require all interns to spend a minimum of 1 week in the pain clinic. Some pain clinics also get residents for a minimum of 2 weeks from almost every specialty, but this practice has not yet become compulsory. The huge number of pain patients mandates that the overwhelming majority of health care for patients with chronic pain must come from primary care providers. Pain specialists can see only those who have special needs for advanced forms of therapy. The crisis in opioid therapy discussed below is primarily due to the prescribing traits of primary care practitioners, not pain specialists. The problem involves not only how physicians are educated, but also what types of people are selected to become physicians. Those who have a biomedical fixation are not likely to deal successfully with chronic pain patients. It seems to me that other health care disciplines have advanced further than medicine in this arena. Medical school curricula are the last vestige of the feudal system in the modern era; change will not be an easy task. The length of the educational process is fixed, and the hours available for teaching are not going to increase. What can be deleted from the existing curriculum to make room for pain? Since most of the faculty of most medical schools are ignorant of pain, how do we get them to replace existing curricular content with pain information? The prevalence of chronic pain and the inadequacies of our current graduates must be used to agitate for change. I cannot say that I am optimistic about this process, but we must do better by our students. A few North American schools of medicine have successfully addressed this issue and have shared their programs in publications.11,12

Pain management is plagued by factionalism. There is no organization that speaks for all of us, and there are no agreed-upon educational or certifying steps; many practitioners function within silos, unaware of what others are learning, saying, or doing. Competing accreditation organizations for individuals and professional societies produce confusion for the public and for organized medicine. Different agendas underlie the efforts of the myriad of professional organizations and publications that claim to represent pain medicine. Guidelines are promulgated that are said to be evidence-based, but often reflect what the members of the guideline-writing committee do for a living or where they stand on a political spectrum, particularly in reference to opioids.13,14 All guidelines reflect the values and preferences of those who write them; they are not really scientific, even though they are said to be based on "evidence." Perhaps we need a David to consolidate the pain professionals and lead us to victory over the Philistines who surround us.

Health care has never been based exclusively upon scientific evidence; indeed, acquisition of such evidence has been relatively novel in the history of medicine, and it is only recently that providers have had the opportunity to apply treatments that have scientifically demonstrated efficacy. Nowhere is this situation more clearly demonstrated than in the use of opioids to treat chronic pain. The first principle here was that acute and chronic pain were very different phenomena; this insight was one of Bonica's most important early contributions. His pain clinic was founded at the University of Washington in 1960, and within a decade its clinicians were swamped with patients who complained of chronic pain yet were taking significant doses of multiple opioids (and other drugs) prescribed by multiple physicians who had no idea what their patients were actually consuming. From this clinical experience, we developed the mantra that it was not wise to treat chronic pain patients with opioids, and we developed treatment strategies to get these patients off their drugs (using the "pain cocktail" approach) and rehabilitate them.15 It did not enter our minds that there could be significant numbers of chronic pain patients who were successfully managed with opioids, because if there were any, we almost never saw them.

In the mid-1980s, several papers were written that challenged the opprobrium surrounding opioids in the management of chronic pain patients.16 The authors appeared to generalize experiences from the treatment of cancer pain patients and reported on a small number of chronic noncancer pain patients who were carefully followed for limited times and "appeared" to do well, meaning that their reports of pain levels were improved but no functional changes were noted. Aberrant, drug-seeking behavior patterns were not observed. These publications fed into the concept that anyone who said "ouch" was entitled to receive opioids in whatever dose they seemed to need. Soon thereafter, the marketing of OxyContin® and the implication that opioids were good for all chronic pain patients led the charge in widespread use of opioids for chronic pain patients in the United States. Opioid prescriptions written by primary care practitioners and pain specialists soared, diversion became a very large problem, and deaths and emergency room visits ascribed to opioids escalated. The inevitable pendulum swing is now occurring, and there is much more concern about opioids for chronic pain patients. Side effects and risks of improper use are now hotly debated.

The fundamental question about efficacy of opioids for chronic pain patients has been lost in the political, economic, and ethical arguments. Scientifically valid data about treatment outcomes are sparse. Pain management in the United States has been badly hurt by this debacle. Similar things have happened in Canada, where the politicians are trying to enforce a special license for prescribing opioids, with mandatory teaching as a prerequisite. In Europe, opioid prescribing has not had such extreme highs and lows; problems with opioid prescriptions for nonmalignant pain were identified earlier than in the United States, and remedial actions were implemented in many countries.17 In many countries and in many U.S. states, the rational use of opioids is now impeded by regulatory agencies and insurers in the attempt to control excessive prescriptions without regard for what is best for a particular patient. Another result of the opioids-for-all movement has been the "pill mills" that seem to be most prevalent in the southeastern United States. Yet another is the expectation by chronic pain patients that they are entitled to receive opioids whenever they hurt. This crisis is primarily due to lack of evidence for the results of chronic opioid administration. Although the treatment of chronic pain may be a basic human right, that does not mean that all patients are entitled to large doses of opioids.18 On the other hand, what is legal to put in one's mouth has never been determined by medical science; it has always has been a social convention. The ethical resolution of this crisis is only to be found in research on this topic, not from consensus panels or legislative mandates. Who is going to fund this research?

The fundamental principle of capitalism is that money motivates behavior. This tenet certainly applies to health care providers; the way the United States favors the reimbursement of procedures over cognitive activities has led to the proliferation of interventional pain specialists and enormous increases in injections and operations for pain in the past 20 years, as well as a reduction in the number of comprehensive multidisciplinary pain clinics. This change has occurred in spite of very little evidence that interventional procedures are beneficial for most chronic pain patients. In countries that have centralized allocation of health care resources, this phenomenon has been controlled to a much larger degree.

No matter how health care is financed, pain management must be included within the pay line. Concerted action is needed on the part of the pain world to influence those who will make such funding decisions; whatever happens to pain management will be part of the grand scheme for the provision of health care. We must be vigilant, for we could be completely omitted from what will be funded. We need to create public demand for our services and secure legislative recognition for the importance of pain management. We need to develop champions in the political arena who will work on behalf of providers and our patients to facilitate the delivery of first-class pain management. This usually means access to multidisciplinary diagnosis and management. Access is compromised both by a shortage of such clinics and by the long patient waiting lists. In Sweden, the government body responsible for health care recently put forth a proposal that every county should have a board to which difficult pain problems would be sent for review. The problems would be evaluated, and if it was deemed necessary, the patients would then be sent for evaluation and treatment to a team composed of a physician, a psychologist, and a physiotherapist. Two Swedish counties have begun this process.

Eleven years ago I contributed an essay to Pain: Clinical Updates and outlined five issues that deserved our attention: defining the mission of pain management, producing outcomes data, showing the public why we matter, figuring out how to get paid for what we need to do, and learning how to continue to provide sympathetic care to our patients. Although some progress has been made on each of these points, it is not enough to make me feel comfortable about our specialty. Of all these issues, I believe that the one that is most critical is the education of health care providers. Pain physicians in academic medicine are the only ones who will address this shortfall, and we must make progress in this area. This endeavor should be independent of the political and economic issues that have enveloped medicine and over which we have little control. We need to redouble our efforts to provide better education for our students and trainees; no one else will do it if we default. And we need to do so with evidence-based clinical data to add to the vastly expanded basic science knowledge of neuroanatomy, neurochemistry, and neuropharmacology. If we fail, I look forward apprehensively to a legislatively mandated curriculum for medical schools: who knows what will be taught then? To be at the whim of legislators or government administrators will, I fear, be the death knell for both scientific and humanistic pain medicine. Health care providers need to care about patients and not see them as customers. The good for the individual patient must take precedence over costs and health system needs. The essence of health care is caring for the patient.


1. Barondess JA. The care of the patient. Pharos 2011(Summer):7–10.

2. National Center for Health Statistics. Health, United States, 2006 with chartbook on trends in the health of Americans. Hyattsville, MD: U.S. Department of Health and Human Services; 2006.

3. Turk DC, Dworkin RH, Burke LB, Gershon R, Rothman M, Scott J, Allen RR, Atkinson JH, Chandler J, Cleeland C, et al.; Initiative on Methods, Measurement and Pain Assessment in Clinical Trials. Developing patient-reported out-
come measures for pain clinical trials: IMMPACT recommendations. Pain 2006;125:208–15.

4. Institute of Medicine Committee on Advancing Pain Research, Care, and Education. Relieving pain in America: blueprint for transforming prevention, care, education, and research. Washington, DC: National Academies Press; 2011.

5. Green CR, Wheeler JR, Marchant B, LaPorte F, Guerrero E. Analysis of the physician variable in pain management. Pain Med 2001;2:317–27.

6. Chang HM, Gallagher R, Vaillancourt PD, Balter K, Cohen M, Garvin B, Charibo C, King SA, Workman EA, McClain B, Ellenberg M, Chiang JS; American Academy of Pain Medicine Undergraduate Education Committee. Undergraduate medical education in pain medicine, end-of-life care, and palliative care. Pain Med 2001;1:224.

7. Upshur CC, Luckmann RS, Savageau JA. Primary care provider concerns about management of pain in community clinic populations. J Gen Int Med 2006;21:652–5.

8. Fishman S. Listening to pain. Waterford Life Sciences; 2006. p. 3.

9. Benedetti C, Dickerson ED, Nichols LL. Medical education: a barrier to pain therapy and palliative care. J Pain Symptom Manage 2001;21:360–1.

10. Lippe PBC, David J, Crossno R, Gitlow S. The First National Pain Medicine Summit—final summary report. Pain Med 2010;11:1447–68.

11. Vadivelu N, Kombo N, Hines RL. The urgent need for pain management training. Acad Med 2009:84:408.

12. Murinson BB, Nenortas E, Mayer RS, Mezei L, Kozachik S, Nesbit S, Haythornthwaite JA, Campbell JN. A new program in pain medicine for medical students: integrating core curriculum knowledge with emotional and reflective development. Pain Med 2011;12:186–95.

13. Perret D, Rosen C. A physician-driven solution: The Association for Medical Ethics, the Physician Payment Sunshine Act, and ethical challenges in pain medicine. Pain Med 2011;12:1361–79.

14. Schatman ME. Editorial: The suppression of evidence-basis in pain medicine and the physician-driven quest to re-establish it. Pain Med 2011;12:1358–60.

15. Sizemore WA. Behavioral aspects of managing medications for chronic pain not caused by cancer. In: Loeser JD, Egan KJ, editors. Managing the chronic pain patient. New York: Raven Press; 1989. p. 117–27.

16. Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain 1986;25:171–86.

17. Eriksen J, Sjøgren P, Bruera E, Ekholm O, Rasmussen NK. Critical issues on opioids in chronic non-cancer pain: an epidemiological study. Pain 2006;125:172–9.

18. Cousins MJ, Brennan F, Carr DB. Pain relief: a universal human right. Pain 2004;112:1–4.

John D. Loeser, MD
Departments of Neurological Surgery and Anesthesiology and Pain Medicine
University of Washington
Seattle, WA 98195, USA


Wednesday, March 21, 2012

Progress in Pain Genetics: A Meeting of Their Own | Pain Research Forum

This is the first of a four-part report on selected talks from the 10th IASP Research Symposium, The Genetics of Pain: Science, Medicine and Drug Development. See also Part 2Part 3, and Part 4or download a PDF of the entire report


Pain researchers convened on 7-9 February 2012 for a first-of-its-kind symposium dedicated to the genetics of pain. The meeting, sponsored by the International Association for the Study of Pain (IASP) and organized by the Genetics and Pain Special Interest Group, drew 120 registrants and 20 faculty to Miami Beach, Florida, US, for talks that ran the gamut from gene discovery in fruit flies to clinical development of ion channel blockers.


The meeting signaled a coming of age for the field of pain genetics. In his talk,Clifford Woolf, Children's Hospital Boston, US, said that he is not a geneticist, but he joined the pain genetics train looking for research tools. "And it has been a wonderful ride—sometimes on a ghost train, sometimes stalled in a siding, and sometimes running out of control and almost derailed." The meeting, he said, showed that the study of the genetics of pain "has become mainstream in neurobiology, and that's exciting."


Of mice (and rats) and men (and women)
The opening session, on preclinical studies of pain genetics, highlighted the central place of rodents in the discovery of pain genes, and in understanding the interplay of genes and environment. The talks showed the power of a translational approach that moves from animals to humans and back again to uncover candidate pain genes, elucidate mechanisms, and validate targets.


Organizers of the 10th IASP Research Symposium, The Genetics of Pain: Science, Medicine and Drug Development (front, from left) Inna Belfer, Roy Levitt, Luda Diatchenko, (rear) William Lariviere, Michael Costigan.

The first speaker of the conference,Marshall Devor, Hebrew University, Jerusalem, Israel, laid the groundwork for talks to come. Discovering genes that influence individual variation in pain sensitivity or risk for chronic pain serves two purposes, he said. First, it opens doors to understanding individual patients: making a diagnosis, illuminating a prognosis, predicting drug responses, or even comforting patients by telling them, "It's not your fault." Second, gene discovery and, in particular, unbiased genomewide methods will benefit many patients by uncovering novel pain mechanisms and potential new treatment targets. The real power, as Devor sees it, is the "promise for finding pathways in the physiology of pain that we never dreamed of before."


The study of monogenetic pain diseases—rare occurrences like familial migraine, congenital insensitivity to pain, or congenital pain syndromes—has illuminated important players in pain pathways. But to identify genes that contribute to more common pain conditions, other approaches are needed. Linkage analysis is used when researchers have access to family members with and without pain. When it is impossible to do family studies (in post-operative pain, e.g., where every family member would have to have had the same operation), the alternative is association studies. Here, groups of unrelated people are compared on a case-control basis to identify genetic variants that are distributed unevenly in those with pain and those without. Association studies test either a limited number of pre-selected genes (a candidate gene approach) or all variants in an unbiased screen (a genomewide approach).


Devor said he believes genomewide association studies (GWAS) in humans are "the path to real discovery," but such investigations are expensive, and so far very few have been funded for pain. He made the case that doing genomewide scans in animals is a way to "jumpstart" human studies, enabling the ultimate identification of human genes at a much lower cost. Identifying mouse strains that vary in the phenotype of choice (or making such lines by selective breeding) allows for the mapping of a phenotype to one or more quantitative trait loci (QTL). This can lead to the identification of the responsible pain gene or genes, which can then be confirmed in humans.


An example of this is the discovery that a variant of the CACNG2 gene is a risk factor for chronic pain after breast surgery (Nissenbaum et al., 2010). More than a decade ago, Devor collaborated with Jeffrey Mogil, McGill University, Montreal, Canada, and others to phenotype a panel of 12 common mouse strains in multiple pain tests, including autotomy after nerve injury, a model of neuropathic pain (Mogil et al., 1999). Further breeding and linkage analysis, and the use of inbred recombinant strains, led to the identification of a locus on chromosome 15 (Seltzer et al., 2001;Devor et al., 2005), which was ultimately narrowed to 155 candidate genes. Using expression data, functional annotation, and single nucleotide polymorphism (SNP) association, Devor and colleagues zeroed in on a single candidate, CACNG2. As the group reported in 2010, when they then looked at variants in the corresponding human gene, they found a haplotype of three SNPs that was associated with an increased risk of pain after mastectomy in a sample of 549 Israeli women, some of whom had pain and some of whom did not.


Marshall Devor. Image credit: William Lariviere.

"If this can be replicated, it's useful," Devor said. Possibly, if a woman is genetically more likely to develop pain, that information may be part of a decision on what type of surgery to have, for example.


CACNG2 encodes the voltage-dependent calcium channel gamma subunit 2 (also known as stargazin), a protein which both regulates the trafficking of AMPA-type glutamate receptors and controls the excitability of neurons. The gene has been implicated in epilepsy, indicating a "deep connection between epilepsy and neuropathic pain having to do with excitability of neural networks," Devor said.

More ...

Tuesday, March 20, 2012

Colonoscopies often come with costly, unnecessary sedation - HealthPop - CBS News

Dread getting a colonoscopy? You're not alone - which is why lots of people are sedated before the procedure. But a new study suggests too many people are getting extra, unnecessary sedation, racking up nearly $1 billion annually in health care costs.

What's more, most of the patients utilizing anesthesiologists to monitor sedation are considered low-risk patients who don't need the extra help, the study authors said.

"These services are not harming patients. They're basically giving them a luxury that is not strictly necessary," said study author, Dr. Soeren Mattke, a senior Rand Corp. scientist. That matters because policymakers are trying to rein in rising medical costs, the authors said.

Patients usually are briefly sedated for a colonoscopy, and some kinds of sedation require monitoring by specialists. That includes use of propofol, a powerful drug that's injected to cause deep sedation and was implicated in pop star Michael Jackson's death. Anesthesiologist-monitored sedation, with or without propofol, is recommended for high-risk patients, including those who are old or sick or previously had complications with anesthesia.

While propofol sedation is also sometimes given to low-risk colonoscopy patients, the study authors say that's often unnecessary. Drugs usually recommended for these patients typically cause lighter sedation, though most patients don't remember anything about the exams afterward. These drugs can be given by the doctor doing the exam, but the study suggests they're often being given and monitored by anesthesiologists, driving up costs.

For the study, published in the March 20 issue of the Journal of the American Medical Association, researchers analyzed insurance claims data on more than 6 million U.S. adults who had the colon exams or imaging scopes of the upper digestive tract between 2003 and 2009. The tests are done to screen for colon cancer, acid reflux and other illnesses.

When the study kicked off, 14 percent of these tests included an anesthesiologist. That climbed to more than 30 percent by 2009. The portion of this extra sedation treatment given to low-risk commercially insured patients remained constant during the study and fell slightly in Medicare fee-for-service patients. But the study authors said far too many low-risk patients are still getting this treatment - more than three-fourths of the commercially insured patients and two-thirds of the Medicare group.

The extra treatment added an average of about $500 to an insured patient's bill in 2009, and $150 to a Medicare bill. In 2009, about 3 million colonoscopies and other digestive scoping tests were done in low-risk patients but included anesthesia services, amounting to $1 billion in potentially unnecessary costs, the study authors estimated.

While some insurance policies exclude coverage for anesthesiologist monitoring for low-risk patients undergoing these exams, insurers sometimes pay for it, Mattke said.

Because of doctor backlash, Aetna, one of the nation's largest health insurers, has indefinitely delayed a policy it tried to implement in 2008 that would have excluded this coverage for low-risk patients, said Dr. James Cross, Aetna's chief of national medical policy and operations.

Reasons for the frequent use of anesthesiologists during these exams vary. Sometimes low-risk patients undergoing colonoscopies and other digestive scoping exams request propofol because they want to be totally unconscious and have heard that it wears off quickly and doesn't cause grogginess, unlike other sedatives, said Dr. John Vargo, a spokesman for the American Society for Gastrointestinal Endoscopy and a digestive specialist at the Cleveland Clinic.

Propofol requires careful monitoring because it has "a narrow window between providing deep sedation and making people stop breathing," and unlike other sedatives, there's no rescue drug to reverse its effects, said Dr. Norm Cohen, vice president for professional affairs at the American Society of Anesthesiologists.

The rising use of anesthesiologists may partly reflect more obese patients and users of Vicodin and other opiate-based prescription drugs, Cohen said. Both may be missed under coding used in the study, but they should be considered at risk because sleep apnea that often accompanies obesity makes sedation trickier, and users of opiate painkillers often require higher than usual doses of sedation, he said.

Vargo said doctors who do the exams can be trained to use propofol in healthy patients, but a journal editorial said some prefer anesthesiologist assistance because it allows them to focus on the colon exam, and if something goes wrong with the sedation, they may not be held legally accountable.

A recent study found the tests actually do what they're supposed to do, HealthPop reported. It found people who underwent a colonoscopy were 53 percent less likely to die from colon cancer, compared with people who didn't get the procedure.

"Sure, it's a pain in the neck. People complain to me all the time, 'It's horrible. It's terrible,'" the study's author Dr. Sidney Winawer, a gastroenterologist at Memorial Sloan-Kettering Cancer Center in New York, said at the time. "But look at the alternative."

Thursday, March 15, 2012

Hospitals Aren’t Hotels -

You should never do this procedure without pain medicine," the senior surgeon told a resident. "This is one of the most painful things we do."

She wasn't scolding, just firm, and she was telling the truth. The patient needed pleurodesis, a treatment that involves abrading the lining of the lungs in an attempt to stop fluid from collecting there. A tube inserted between the two layers of protective lung tissue drains the liquid, and then an irritant is slowly injected back into the tube. The tissue becomes inflamed and sticks together, the idea being that fluid cannot accumulate where there's no space.

I have watched patients go through pleurodesis, and even with pain medication, they suffer. We injure them in this controlled, short-term way to prevent long-term recurrence of a much more serious problem: fluid around the lungs makes it very hard to breathe.

A lot of what we do in medicine, and especially in modern hospital care, adheres to this same formulation. We hurt people because it's the only way we know to make them better. This is the nature of our work, which is why the growing focus on measuring "patient satisfaction" as a way to judge the quality of a hospital's care is worrisomely off the mark.

For several years now, hospitals around the country have been independently collecting data in different categories of patient satisfaction. More recently, the Centers for Medicare and Medicaid Services developed the Hospital Consumer Assessment of Healthcare Providers and Systems survey and announced that by October 2012Medicare reimbursements and bonuses were going to be linked in part to scores on the survey.

The survey evaluates behaviors that are integral to quality care: How good was the communication in the hospital? Were patients educated about all new medications? On discharge, were the instructions the patient received clear?

These are important questions. But implied in the proposal is a troubling misapprehension of how unpleasant a lot of actual health care is. The survey measures the "patient experience of care" to generate information important to "consumers." Put colloquially, it evaluates hospital patients' level of satisfaction.

The problem with this metric is that a lot of hospital care is, like pleurodesis, invasive, painful and even dehumanizing. Surgery leaves incisional pain as well as internal hurts from the removal of a gallbladder or tumor, or the repair of a broken boneChemotherapy weakens the immune system. We might like to say it shouldn't be, but physical pain, and its concomitant emotional suffering, tend to be inseparable from standard care.

What's more, recent research suggests that judging care in terms of desirable customer experiences could be expensive and may even be dangerous. A new paper by Joshua Fenton, an assistant professor at the University of California, Davis, and colleagues found that higher satisfaction scores correlated with greater use of hospital services (driving up costs), but also with increased mortality.

The paper examined patient satisfaction only with physicians, rather than hospitals, and the link between satisfaction and death is obviously uncertain. Still, the results suggest that focusing on what patients want — a certain test, a specific drug — may mean they get less of what they actually need.

In other words, evaluating hospital care in terms of its ability to offer positive experiences could easily put pressure on the system to do things it can't, at the expense of what it should.

To evaluate the patient experience in a way that can be meaningfully translated to the public, we need to ask deeper questions, about whether our procedures accomplished what they were supposed to and whether patients did get better despite the suffering imposed by our care.

We also need to honestly assess our treatment of patients for whom curative care is no longer an option.

I had such a patient. He was an octogenarian, but spry, and he looked astoundingly healthy. He'd been sent to us with a newly diagnosed blood cancer, along with a promise from the referring hospital that we could make him well.

But we couldn't. He was too old to tolerate the standard chemotherapy, the medical fellow on duty told him. When I came into his room a little later he said to me, with a stunned and yearning look, "Well, he made it sound like I don't have a lot of options." The depth of alienation, hopelessness and terror that he was feeling must have been unbearable.

The final questions on the survey ask patients to rate the hospital on a scale from worst to best, and whether they would recommend the hospital to family and friends. How would my octogenarian patient have answered? A physician in our hospital had just told him that he would die sooner than expected. Did that make us the best hospital he'd ever been in, or the worst?

Hospitals are not hotels, and although hospital patients may in some ways be informed consumers, they're predominantly sick, needy people, depending on us, the nurses and doctors, to get them through a very tough physical time. They do not come to us for vacation, but because they need the specialized, often painful help that only we can provide. Sadly, sometimes we cannot give them the kind of help they need.

If the Centers for Medicare and Medicaid is to evaluate the patient experience and link the results to reimbursement, it needs to incorporate questions that address the complete and expected hospital experience. It's fair and even valuable to compare hospitals on the basis of how well they maintain standards of patient engagement. But a survey focused on "satisfaction" elides the true nature of the work that hospitals do. In order to heal, we must first hurt.

Theresa Brown, an oncology nurse, is a contributor to The New York Times's Well blog and the author of "Critical Care: A New Nurse Faces Death, Life and Everything in Between."

Wednesday, March 14, 2012

Panel Backs Continued Testing of Pain Drugs -

A federal advisory panel unanimously said a class of experimental arthritis-pain drugs from Pfizer Inc. and other companies should continue to be developed, although some panel members suggested limiting study to patients who failed other therapies.

The bulk of clinical studies involving the drugs, known as antinerve growth factors, were put on hold in 2010 following reports that some patients' osteoarthritis rapidly worsened to the point of requiring joint replacement surgeries.

According to the U.S. Food and Drug Administration, there are three companies that have conducted studies involving anti-NGF agents—with Pfizer the furthest along in development with its drug called tanezumab. A unit of Johnson & Johnson and Regeneron Pharmaceuticals Inc. each have similar drugs in development.

The drugs, designed to be given by injection, either intravenously or by needle, work by blocking a protein called nerve growth factor, which is believed to contribute to pain.

In 2010, the FDA asked Pfizer to temporarily suspend testing of tanezumab after data from clinical studies of the drug in osteoarthritis patients showed some patients had their condition rapidly worsen to the point they needed a joint replacement. Most studies from Regeneron and Johnson & Johnson were also put on hold, although the FDA did allow cancer-related pain studies to continue.

It isn't clear if the drugs actually caused joint destruction to worsen. One theory is that the drugs masked the pain in some patients so well that they increased their activity and accelerated the rate of damage to their knees or hips, for example.

The agency's arthritis drugs advisory panel, which is made up of non-FDA medical experts, said clinical data collected to date suggests there is a warning signal showing a certain type of rapid joint destruction among some patients exposed to the drugs, but that it wasn't enough to end development. The panel also said it is possible that nonsteroidal anti-inflammatory drugs, or NSAIDS, added to the risk of rapid joint destruction.

Several panel members also said there is a need for new kinds of pain medicines.

"The risk of currently used available agents—NSAIDS and opioids—is very high," said Lenore Buckley the chair of the panel and an internal medicine professor at Virginia Commonwealth University School of Medicine in Richmond. "Not many people want to say, let's just give up on this class of medications at this point."

The panel voted 21-0 in favor of a question that asked whether there was a role for continued development of the drugs. The panel then voted 20-1 in favor of a question that asked whether development of the drugs should be continued for pain conditions that currently don't have good treatments like chronic pancreatitis.

FDA officials said if they allow development of the drugs to continue more broadly that they would hold advisory panel meetings before any drug would be allowed to be marketed.

Pfizer said it believes studies of tanezumab in osteoarthritis should be allowed but has proposed certain restrictions such as using a lower dose and discontinuing use of tanezumab in patients who may not initially respond to treatment. The company is also proposing to study the product as a single therapy and not combined with nonsteroidal anti-inflammatory drugs, or NSAIDs.