September is Pain Awareness Month

The month of September has been declared Pain Awareness Month.  Pain Awareness Month is a time when various organizations work to raise public awareness of issues in the area of pain and pain management. 

The first Pain Awareness Month was in 2001, when the ACPA led a coalition of groups to establish September as Pain Awareness Month.  ACPA established Partners for Understanding Pain and 80 organizations, both health care professionals and consumer groups, including the NAACP supported the effort. 

The key to raising awareness is to get involved.   There are many things that you can do to help promote Pain Awareness Month more ...

These days it is easy to get irritated with the exaggerated interpretations of brain imaging — for example, that a single fMRI scan can reveal our innermost feelings — and with inflated claims about our understanding of the biological basis of our higher mental processes.

Such irritation has led a number of thoughtful people to declare that we can never achieve a truly sophisticated understanding of the biological foundation of complex mental activity.

In fact, recent newspaper articles have argued that psychiatry is a “semi-science” whose practitioners cannot base their treatment of mental disorders on the same empirical evidence as physicians who treat disorders of the body can. The problem for many people is that we cannot point to the underlying biological bases of most psychiatric disorders. In fact, we are nowhere near understanding them as well as we understand disorders of the liver or the heart.

But this is starting to change.

Consider the biology of depression. We are beginning to discern the outlines of a complex neural circuit that becomes disordered in depressive illnesses. Helen Mayberg, at Emory University, and other scientists used brain-scanning techniques to identify several components of this circuit, two of which are particularly important.

One is Area 25 (the subcallosal cingulate region), which mediates our unconscious and motor responses to emotional stress; the other is the right anterior insula, a region where self-awareness and interpersonal experience come together.

These two regions connect to the hypothalamus, which plays a role in basic functions like sleep, appetite and libido, and to three other important regions of the brain: the amygdala, which evaluates emotional salience; the hippocampus, which is concerned with memory; and the prefrontal cortex, which is the seat of executive function and self-esteem. All of these regions can be disturbed in depressive illnesses.

In a recent study of people with depression, Professor Mayberg gave each person one of two types of treatment: cognitive behavioral therapy, a form of psychotherapy that trains people to view their feelings in more positive terms, or an antidepressant medication. She found that people who started with below-average baseline activity in the right anterior insula responded well to cognitive behavioral therapy, but not to the antidepressant. People with above-average activity responded to the antidepressant, but not to cognitive behavioral therapy. Thus, Professor Mayberg found that she could predict a depressed person’s response to specific treatments from the baseline activity in the right anterior insula.

These results show us four very important things about the biology of mental disorders. First, the neural circuits disturbed by psychiatric disorders are likely to be very complex.

Second, we can identify specific, measurable markers of a mental disorder, and those biomarkers can predict the outcome of two different treatments: psychotherapy and medication.

Third, psychotherapy is a biological treatment, a brain therapy. It produces lasting, detectable physical changes in our brain, much as learning does.

And fourth, the effects of psychotherapy can be studied empirically. Aaron Beck, who pioneered the use of cognitive behavioral therapy, long insisted that psychotherapy has an empirical basis, that it is a science. Other forms of psychotherapy have been slower to move in this direction, in part because a number of psychotherapists believed that human behavior is too difficult to study in scientific terms.

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Any discussion of the biological basis of psychiatric disorders must include genetics. And, indeed, we are beginning to fit new pieces into the puzzle of how genetic mutations influence brain development.

Most mutations produce small differences in our genes, but scientists have recently discovered that some mutations give rise to structural differences in our chromosomes. Such differences are known as copy number variations.

People with copy number variations may be missing a small piece of DNA from a chromosome, or they may have an extra piece of that DNA.

Matthew State, at the University of California, San Francisco, has discovered a remarkable copy number variation involving chromosome 7. An extra copy of a particular segment of this chromosome greatly increases the risk of autism, which is characterized by social isolation. Yet the loss of that same segment results in Williams syndrome, a disorder characterized by intense sociability.

This single segment of chromosome 7 contains about 25 of the 21,000 or so genes in our genome, yet an extra copy or a missing copy has profound, and radically different, effects on social behavior.

The second finding is de novo point mutations, which arise spontaneously in the sperm of adult men. Sperm divide every 15 days. This continuous division and copying of DNA leads to errors, and the rate of error increases significantly with age: a 20-year-old will have an average of 25 de novo point mutations in his sperm, whereas a 40-year-old will have 65. These mutations are one reason older fathers are more likely to have children with autism and schizophrenia.

Our understanding of the biology of mental disorders has been slow in coming, but recent advances like these have shown us that mental disorders are biological in nature, that people are not responsible for having schizophrenia or depression, and that individual biology and genetics make significant contributions.

The result of such work is a new, unified science of mind that uses the combined power of cognitive psychology and neuroscience to examine the great remaining mysteries of mind: how we think, feel and experience ourselves as conscious human beings.

This new science of mind is based on the principle that our mind and our brain are inseparable. The brain is a complex biological organ possessing immense computational capability: it constructs our sensory experience, regulates our thoughts and emotions, and controls our actions. It is responsible not only for relatively simple motor behaviors like running and eating, but also for complex acts that we consider quintessentially human, like thinking, speaking and creating works of art. Looked at from this perspective, our mind is a set of operations carried out by our brain. The same principle of unity applies to mental disorders.

In years to come, this increased understanding of the physical workings of our brain will provide us with important insight into brain disorders, whether psychiatric or neurological. But if we persevere, it will do even more: it will give us new insights into who we are as human beings.

“The New Science of Mind” by Eric R. Kandel in The New York Times on September 6, 2013.  

Eric R. Kandel, a professor at the Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia, a senior investigator at the Howard Hughes Medical Institute and a recipient of the 2000 Nobel Prize in Physiology or Medicine, is the author of “The Age of Insight: The Quest to Understand the Unconscious in Art, Mind and Brain, From Vienna 1900 to the Present.”

A team of University of California, Riverside researchers have developed a novel transparent skull implant that literally provides a “window to the brain”, which they hope will eventually open new treatment options for patients with life-threatening neurological disorders, such as brain cancer and traumatic brain injury.

The team’s implant is made of the same ceramic material currently used in hip implants and dental crowns, yttria-stabilized zirconia (YSZ). However, the key difference is that their material has been processed in a unique way to make it transparent.

Since YSZ has already proven itself to be well-tolerated by the body in other applications, the team’s advancement now allows use of YSZ as a permanent window through which doctors can aim laser-based treatments for the brain, importantly, without having to perform repeated craniectomies, which involve removing a portion of the skull to access the brain.

The work also dovetails with President Obama’s recently-announced BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, which aims to revolutionize the understanding of the human mind and uncover new ways to treat, prevent, and cure brain disorders. The team envisions potential for their YSZ windows to facilitate the clinical translation of promising brain imaging and neuromodulation technologies being developed under this initiative.

“This is a case of a science fiction sounding idea becoming science fact, with strong potential for positive impact on patients,” said Guilermo Aguilar, a professor of mechanical engineering at UC Riverside’s Bourns College of Engineering (BCOE).

Aguilar is part of 10-person team, comprised of faculty, graduate students and researchers from UC Riverside’s Bourns College of Engineering and School of Medicine, who recently published a paper “Transparent Nanocrystalline Yttria-Stabilized-Zirconia Calvarium Prosthesis” about their findings online in the journal Nanomedicine: Nanotechnology, Biology and Medicine.  

Laser-based treatments have shown significant promise for many brain disorders. However, realization of this promise has been constrained by the need for performing a craniectomy to access the brain since most medical lasers are unable to penetrate the skull. The transparent YSZ implants developed by the UC Riverside team address this issue by providing a permanently implanted view port through the skull.  

“This is a crucial first step towards an innovative new concept that would provide a clinically-viable means for optically accessing the brain, on-demand, over large areas, and on a chronically-recurring basis, without need for repeated craniectomies,” said team member Dr. Devin Binder, a clinician and an associate professor of biomedical sciences at UC Riverside.

Although the team’s YSZ windows are not the first transparent skull implants to be reported, they are the first that could be conceivably used in humans, which is a crucial distinction. This is due to the inherent toughness of YSZ, which makes it far more resistant to shock and impact than the glass-based implants previously demonstrated by others. This not only enhances safety, but it may also reduce patient self-consciousness, since the reduced vulnerability of the implant could minimize the need for conspicuous protective headgear.

In addition to Aguilar and Binder, authors of the paper are: Yasaman Damestani, a Ph.D. student working with Aguilar; B. Hyde Park, an assistant professor of bioengineering; Carissa L. Reynolds, a Ph.D. student working with Park; Javier E. Garay, an associate professor of mechanical engineering; Yasuhiro Kodera, a project scientist who works in Garay’s lab; Masaru P. Rao, an assistant professor of mechanical engineering; Jenny Szu, a lab technician in Binder’s lab; and Mike S. Hsu, a staff research associate in Binder’s lab.

This research was supported, in part, by the UC Riverside Chancellor’s Strategic Research Initiative.

“Creating a 'Window to the Brain',” by Sean Nelson for UCR Today on September 3, 2013

Women have long been thought to have much higher rates of depression than men, but when alternative and traditional symptoms of depression are considered, these sex disparities disappear, new research shows.

"The sex differences framework is rooted in the idea that the construct of depression is the same in men and women and seeks to investigate sex differences in a range of related variables, including symptoms," investigators led by Lisa A. Martin, PhD, from the University of Michigan, Dearborn, write.

"Although this has been a popular approach to date, it is often critiqued for relying on oppositional binaries that understand 'male depression' only as it is contrasted with 'female depression,' which fails to acknowledge the heterogeneity that exists within these groups."

The study was published online August 28 in JAMA Psychiatry.

More Anger, Aggression in Men

The aim of the study was to explore whether sex disparities in depression rates disappear when other symptoms besides conventional depression symptoms are considered.

The researchers used data from the National Comorbidity Survey Replication (NCS-R), a nationally representative survey of the incidence and prevalence of mental disorders among English-speaking adults in the United States.

The survey included 3310 women and 2382 men. Their mean age was 45.2 years, 73.4% were non-Hispanic white, and 51.6% had some education beyond high school. The mean annual household income was $59,575. The mean income for men was $63,365, and for women, it was $49,327.

The researchers developed 2 scales. The first, the Male Symptoms Scale (MSS), included alternative male-type symptoms of depression, including irritability, anger attacks/aggression, sleep disturbance, alcohol or drug abuse, risk-taking behavior, hyperactivity, stress, and loss of interest in pleasurable activities.

The second scale, the Gender Inclusive Depression Scale (GIDS), included all of the MSS symptoms, plus 7 traditional symptoms of depression, including sad/depressed mood, loss of vitality, tiredness, ambivalence, anxiety/uneasiness, and complaintiveness or feeling pathetic.

Using the MSS scale that included alternative, male-type symptoms of depression, the researchers found a higher prevalence of depression in men (26.3%) than in women (21.9%) (P = .007).

The researchers also found that men reported significantly higher rates of anger attacks/aggression, substance abuse, and risk-taking behavior compared with women.

More Stress, Irritability in Women

Women, on the other hand, reported significantly greater rates of stress, irritability, sleep problems, and loss of interest in things they usually enjoyed, such as work, hobbies, and personal relationships.

No sex difference in the prevalence of depression as assessed by the GIDS that included alternative and traditional depression symptoms was found. According to that scale, 30.6% of men and 33.3% of women met criteria for depression.

In terms of severity of depression, the researchers found that 63.2% of men and 62.0% of women fell into the mild category, meaning that they had 1 to 4 symptoms; 28.3% of men and 28.9% of women fell into the moderate category, with 5 to 9 symptoms; and 8.5% of men and 9.1% of women fell into the severe category, with 10 to 15 symptoms. No significant sex differences were demonstrated at any severity level, they report.

"These results suggest that relying only on men's disclosure of traditional symptoms could lead to an underdiagnosis of depression in men and that clinicians should consider other clues when assessing depression in men," the authors write.

They also point out that "despite the significant findings reported in this study, there are noteworthy limitations."

One limitation was that the study did not include symptoms among men such as overworking, overexercising, changing their sexual behavior, or gambling. Also, items that assessed taking chances or reckless behavior were not linked to an emotional condition. Future studies should include items that assess the excluded behaviors, the authors suggest.

They conclude that the results of their study have the potential to bring "significant advances to the field in terms of the perception and measurement of depression. These findings could lead to important changes in the way depression is conceptualized and measured."

By Fran Lowry for Medscape on Aug 29, 2013

‘Migraine Linked to Structural Brain Changes’ by Pauline Anderson for Medscape on Aug 28, 2013:

A new literature review confirms that compared with patients without migraine, those with migraine have more white matter abnormalitiies (WMAs), infarct-like lesions (ILLs), and volumetric changes in gray and white matter regions of the brain, although the cllnical and functional significance of these lesions is still uncertain.

The analysis showed that the association between migraine and structural changes in the brain is stronger among those who experience migraine with aura.

The results challenge the widely accepted notion that migraine is a benign primary headache with no long-term consequences or sequelae for the brain.

"Our study, based on a systematic review and meta-analysis, suggests the opposite: that this primary headache disorder may permanently change the brain structure," said author Sait Ashina, MD, headache program director, Beth Israel Medical Center, and assistant professor, neurology and anesthesiology, Albert Einstein College of Medicine, New York, New York.

However, Dr. Ashina cautioned that not all the evidence is in yet and that prospective longitudinal studies are needed to confirm the influence of migraine on brain structure. 

The study was published online August 28 more …

Levels of calcitonin gene-related peptide (CGRP), a neurotransmitter that causes vasodilation, are elevated in the peripheral blood of women with chronic migraine (CM), and to a lesser extent in women with episodic migraine, compared with levels in healthy controls without a history of headache, new research reveals.

The study shows, for the first time, increased CGRP levels in patients with CM outside migraine attacks and in the absence of medication for symptoms.

The results suggest that CGRP levels could be used as a biomarker for permanent trigeminovascular activation and therefore help diagnose chronic migraine. Until now, the diagnosis of primary headache has been based only on clinical grounds.

"It's important to have biomarkers, not only to avoid misdiagnoses but also for treatment follow-up," said study author Julio Pascual, MD, PhD, director, Neuroscience Department, and professor, neurology, University Hospital Central de Asturias, Oviedo, Spain.

"Can you imagine diagnosing and treating diabetes only on clinical grounds? That's what we do now in primary headaches. Chronic migraine is the most frequent type of almost daily headache, and it's very disabling."

The study was published online August 23 in Neurology.

Throbbing Pain

It is well established that during a migraine attack, trigeminal activation leads to release of CGRP from presynaptic nerve terminals. This facilitates a peripheral inflammatory and vasodilatory response and causes activation of neurons involved in pain transmission, the authors note. This explains the typically throbbing pain experienced by people suffering a migraine.

CM is defined at least 15 headache days per month for at least 3 months. Fewer than 15 headache days per month is considered episodic migraine (EM).

Using the right antecubital vein, researchers obtained blood samples from participants who were not experiencing moderate or severe pain and had not taken medication for symptoms in the previous 24 hours. For ethical reasons, participants could continue daily preventive medications, and most with migraine were taking these agents. The investigators determined CGRP levels using a commercial enzyme-linked immunosorbent assay kit.

The study included 103 women with CM (mean age, 43.1 years), 31 matched healthy women with no headache history (mean age, 38.6 years), 43 women with EM (mean age, 44.4 years), and 14 patients with episodic cluster headache (including 13 men; mean age, 45.4 years) matched for age in a pain-free period.

Study participants underwent a general physical and neurologic examination. Those with EM and CM had at least a normal neuroimaging examination.

The analysis showed that CGRP levels were significantly higher in women with CM (74.90 pg/mL) than in control women (33.74 mg/mL; P < .001), women with EM (46.37 pg/mL; P < .001 vs CM and P < .005 vs controls) and to patients with episodic cluster headache (45.87 pg/mL).

"Increased peripheral CGRP levels should be interpreted as a distant sign of activation of the trigeminovascular system; because its molecule is so large, CGRP cannot pass the blood-brain barrier," said the authors.

Thresholds of 43.45 and 58.22 pg/mL optimize the sensitivity and specificity to differentiate patients with CM from healthy controls and patients with EM, respectively, according to the authors.

Migraine With Aura

A total of 46 women with CM had a history of migraine with aura attacks. CGRP levels were significantly higher in these women than in those who had never experienced an aura. However, only 4 patients experienced at least 1 aura per month.

According to the authors, there are several potential explanations for this finding. It could, for example, support the proposal that the pathophysiologic mechanism of the aura, the cortical spreading depression phenomenon, is enough to activate sensory nerve terminals around pial blood vessels.

Among women with EM, CGRP was not significantly elevated in the 21 women with aura compared with the 22 with no aura antecedents.

Among the women with CM, CGRP levels were not significantly different in patients meeting criteria for analgesic overuse. "Even considering that all of the women in our study with CM meeting overuse criteria had tried formal withdrawal of symptomatic medications at least once and for 2 months without success, these results are a further proof that both subtypes of CM, with and without analgesic overuse, would share the same pathophysiologic substrate," the authors write.

Other variables, such as age, depression, fibromyalgia, vascular risk factors, history of triptan use, and type of preventive treatment, also did not influence CGRP levels.

The fact that patients were taking preventive medications could be considered a limitation of the study but could also make the results more relevant because, as the authors point out, these drugs could reduce trigeminovascular system activation, resulting in a decrease in CGRP release.

Although the new study had other potential limitations, such as the use of a select headache clinic population, "it seems that interictal CGRP levels are somewhat specific and sensitive for CM in the context of a patient with daily or almost daily headaches and a history of migraine, which could be of great help on sharpening the diagnosis of the primary headache disorders and supports the proposal of a key role of CGRP of sensitization of pain circuits leading to CM," the authors concluded.

Using CGRP as a biomarker for CM may not be that far off from clinical practice, if the current results are confirmed in other studies using this neuropeptide, perhaps together with other pain-producing peptides, said Dr. Pascual. Such studies, he said, would not be difficult to carry out.

"My prediction is that clinical trials in chronic migraine that include the follow-up of CGRP levels will begin soon after publication of our study," he said.

And, he said, it won't be long before hospitals will start using CGRP levels to routinely follow patients with CM because this testing is neither very expensive nor difficult to perform.

Monitor Status

In an accompanying article, Stephen D. Silberstein, MD, Jefferson Headache Center, Jefferson Center for Neuroscience, Philadelphia, Pennsylvania, and Lars Edvinsson, MD, Internal Medicine, Lund University, Sweden, agreed the study demonstrates that peripheral CGRP levels may be a biomarker for CM.

Physicians could use CGRP levels outside migraine attacks, and in the absence of medication for symptoms, to monitor a patent's status and response to preventive treatment, they write.

"Future work on the role of CGRP and its receptor in CNS and intracranial structures will be very interesting," they write. "In particular, we look forward to learning more about the effects of small-molecule CGRP antagonists and antibodies toward CGRP and the CGRP receptor on CGRP levels and clinical outcome."

They noted that until now, CGRP elevations in plasma have not been reproduced in all studies but that technical problems have at times hampered the proper measurements of this neuropeptide.

Dr. Pascual served on the scientific advisory boards of Allergen and MSD. 

“Neuropeptide May Be Biomarker for Chronic Migraine” by Pauline Anderson for Medscape on Aug 27, 2013

Make sure that patients understand their condition, take their medicine and see their primary care doctors so they don’t wind up back in the hospital. Common sense things, right?  Only until the Affordable Care Act threatened hospitals with the loss of money, however, did such coordination of care start to become common.

Four out of five hospital in Florida still “re-admit” too many patients, but the law is pushing them to improve care.  It is a less-publicized but crucial component of the law that Republicans have voted 40 times to repeal, delay or defund.  New Gingrich, who railed against the law as a presidential candidate, blasted fellow Republicans Wednesday for not having a viable alternative to it.

Make sure that patients understand their condition, take their medicine and see their primary care doctors so they don’t wind up back in the hospital.  Common sense things, right?  Only until the Affordable Care Act threatened hospitals ith the loss of money, however, did such coordination of care start to become common.

Speaking at the Republican National Committee’s summer meeting, Mr. Dingrich said, “I will bet you, for most of you, you go home in the next two weeks when your members of Congress are home, and you look them in the eye and you say, ‘What is your positive replacement for Obamacare?’ They will have zero answer.”

Indeed.  The law is hardly perfect.  But even though it won’t take full effect until 2015, it is already having a positive impact on health care quality.  The law rewards doctors and hospitals for improving care to Medicare patients and penalizes them when patients get sicker as a result of poor coordination and follow-up.  One measure is excessive hospital readmissions.

As the Post’s Stacey Singer reported, 80 percent of Florida hospitals will be penalized by Medicare next year for above-average readmission rates, including nine out of 13 Palm Beach County hospitals.  The penalties are forcing hospitals to make quality of care, not quantity of care, the priority.

Jupiter Medical Center, a nonprofit that recently held a summit on improving post-release coordination of care, is one of the four hospitals that will not see a penalty.  The others include Bethesda Health in Boynton Beach, which owns Bethesda Hospital East and Bethesda Hospital West, and Boca Raton Regional, all of which also are independent nonprofits.  Tenet Healthcare’s Good Samaritan Medical Center, a for-profit that received a .02 percent penalty for 2013, improved enough to become the fourth.

This is the second year that Boca Raton Regional, which sees a large number of Medicare patients, has escaped penalties.  Chief Medical Officer Dr. Charles Posternack said most patients are highly educated and affluent, which makes transition of care less challenging than for other hospitals.  He said educating patient about their disease and medications is key, along with ensuring follow-up care.

“It’s the culture of the hospital,” Dr. Posternack said.  “It’s important not just to get them to have to come back in again because you just didn’t do a good job.”  Is this what Republican critics of the Affordable Care Act want to repeal, delay and defund?

“The good: Better hospitals” by Rhonda Swan in The Palm Beach Post on August 16, 2013

On Thursday, U.S. Department of Health and Human Services Secretary Kathleen Sebelius held a media call and press conference in Tampa to announce new Affordable Care Act grants to help consumers enroll in insurance plans.  There was no such announcement, however, when the administration decided months ago to delay for some insurers the limit on out-of-pocket expenses the can impose on insurers.

There is a case to be made for the administration latest delay of a key provision in the law.  But because the delay doesn’t make the law look good, the administration buried the announcement online in a February FA Q put out by HHS and the Labor and Treasury departments.

The health care law is complex, and implementing its numerous provisions will be a challenge for the administration.  But it’s not as if the country hasn’t been here before, and recently.  Consider the rollout of Medicare Part D, the prescription drug program, in 2005.

“Although the officials implementing Part D encountered significant technical, educational, and coordination difficulties at first, eight years later … the public generally views the program as a success,” says a June study by the Center on Health Insurance Reforms.  The center looked at Part D for lessons on implementing the Affordable Care Act.  “While flaws remain,” the Part D study said, “a program born amidst partisan controversy and launched with considerable wariness has emerged to become a core part of Medicare.”

Such partisan controversy makes the Obama administration wary of communicating anything about the health care law that could be deemed negative.  Last month, the administration used a blog post to announce a one-year delay of the employer mandate.  Though Kaiser Health News reported the new delay in April, opponents of the law didn’t pounce on the issue until the New York Times reported it this week.

Beginning in 2014, the law caps annual out-of-pocket costs at $6,350 for individuals and $12,500 for families.  The provision will not be enforced for some employer insurance plans, though, until 2015.

Those employers have separate benefit managers for different parts of their coverage, such as medical care and drugs.  Their technical systems can’t communicate with one another yet.  Out-of-pocket limits will be enforced for all plans on the insurance exchanges, plans with only one administrator, and all new plans.

It’s not the disaster opponents make it out to be.  But it is a setback for consumers with chronic ailments and high drug costs.  The administration should just say that.

“The bad: Too much secrecy” by Rhonda Swan in The Palm Beach Post on August 16, 2013