Thursday, November 27, 2008
The drug, for which a trade name has not yet been established, is a centrally acting analgesic that will be available in doses of 50, 75, and 100 mg.
"This approval offers healthcare professionals an additional choice for treating moderate to severe pain," John Jenkins, MD, director of the office of new drugs at the FDA's Center for Drug Evaluation and Research, said in a statement from the FDA.
The drug acts as both an opioid and nonopioid agent, the FDA release notes. It acts primarily as a mu-opioid-receptor agonist but also inhibits reuptake of norepinephrine, which may also have an analgesic effect.
A statement from Johnson & Johnson notes that following this FDA approval, "as per federal regulation for all controlled substances, tapentadol will be reviewed by the US Drug Enforcement Administration for scheduling, and it cannot be sold until it receives a scheduling classification."
"Opioids are considered safe and effective in selected patients but can cause dependence, abuse, and addiction," the FDA release adds. "All patients treated with opioids require careful monitoring by their healthcare professional for signs of abuse."
The approval was based on data from clinical studies involving more than 2100 patients, the Johnson & Johnson release notes. These phase 3 studies, presented at the 27th Annual Scientific Meeting of the American Pain Society in May, showed significant relief compared with placebo for patients undergoing bunionectomy, a common foot surgery; in pain from end-stage joint disease; and with low back pain or osteoarthritis of the hip or knee. It was generally well tolerated.
The most common adverse effects from tapentadol are nausea, dizziness, vomiting, sleepiness, and headaches, the FDA release said. "The labeling for tapentadol includes warnings about the risk of respiratory depression; addictive depressive effects on the central nervous system when taken with alcohol, other opioids, or illicit drugs; and abuse potential," the FDA release adds.
In its statement, the company also notes that the new drug is contraindicated in any situation where mu-opioids are contraindicated, such as in significant respiratory depression, acute or severe bronchial asthma, or hypercapnia; in patients with paralytic ileus; or in those who are currently using or are within 14 days of using monoamine oxidase inhibitors (MAOIs). The drug should be prescribed "with care" in patients with a history of a seizure disorder or any condition that would put the patient at risk for seizures.
Finally, the Johnson & Johnson release points out that a potentially life-threatening serotonin syndrome may occur with tapentadol, "particularly with concomitant use of serotonergic drugs such as [selective serotonin-reuptake inhibitors] SSRIs, [serotonin-norepinephrine-reuptake inhibitors] SNRIs, [tricyclic antidepressants] TCAs, MAOIs, and triptans and with drugs that impair metabolism of serotonin (including MAOIs)."
The new finding by scientists at Northwestern University's Feinberg School of Medicine, begins to explain a mysterious condition that the medical community had doubted was real.
The people whose brains were examined have a chronic pain condition called complex region pain syndrome (CRPS.) It's a pernicious and nasty condition that usually begins with an injury causing significant damage to the hand or the foot. For the majority of people, the pain from the injury disappears once the limb is healed. But for 5 percent of the patients, the pain rages on long past the healing, sometimes for the rest of people's lives. About 200,00 people in the U.S. have this condition.
In a hand injury, for example, the pain may radiate from the initial injury site and spread to the whole arm or even the entire body. People also experience changes in skin color to blue or red as well as skin temperature (hotter at first, then becoming colder as the condition turns chronic.) Their immune system also shifts into overdrive, indicated by a hike in blood immune markers.
The changes in the brain take place in the network of tiny, white "cables" that dispatch messages between the neurons. This is called the brain's white matter. Several years ago, Northwestern researchers discovered chronic pain caused the regions in the brain that contain the neurons -- called gray matter because of it looks gray -- to atrophy.
This is the first study to link pain with changes in the brain's white matter. It will be published November 26 in the journal Neuron.
"This is the first evidence of brain abnormality in these patients," said A. Vania Apkarian, professor of physiology at the Feinberg School and principal investigator of the study. " People didn't believe these patients. This is the first proof that there is a biological underpinning for the condition. Scientists have been trying to understand this baffling condition for a long time."
Apkarian said people with CRPS suffer intensely and have a high rate of suicide. "Physicians don't know what to do," he said. "We don't have the tools to take care of them."
The new findings provide anatomical targets for scientists, who can now look for potential pharmaceutical treatments to help these patients, Apkarian said. He doesn't know yet if chronic pain causes these changes in the brain or if CRPS patients' brains have pre-existing abnormalities that predispose them to this condition.
In the new study, the brains of 22 subjects with CRPS and 22 normal subjects were examined with an anatomical MRI and a diffusion tensor MRI, which enabled scientists to view the white matter. In addition to changes in white matter, the CRPS patients' brains showed an atrophy of neurons or gray matter similar to what has been previously shown in other types of chronic pain patients.
Apkarian said the white matter changes in patients' brains is related to the duration and intensity of their pain and their anxiety. It is likely that white matter reorganizes in other chronic pain conditions as well, but that has not yet been studied, he noted.
Wednesday, November 26, 2008
Fighting a serious infection that left her in the hospital for a week, Lisa at Rest Ministries shares how this Thanksgiving has new priorities and joys that previous holidays didn’t have, and how she’s learning contentment while dealing with the challenges of recovery.
Rosalind at Working with Chronic Illness presents Thanksgiving - Is It About Turkey or Thanks?, with the top 5 things she’s thankful for.HealthSkills writes about the concept of acceptance, a big challenge when you have chronic pain.
CRPS-RSD A Better Life connects the US president-Elect Obama’s speech Yes, We Can to our own goals of living fully despite pain.Ordinary Miracles notes our poor understanding of CFS (Chronic Fatigue Syndrome) - we’re not sure what to call it, we’re uncertain what causes it, and we’re not great at treating it.
The Back Pain Blog writes about an alternative treatment to steroid injections, in his education series about sciatic nerve pain.
Psychology of Pain links to the Washington Post’s article about the cause of Gulf War Illness, a disease which includes pain, headaches and fatiguehttp://www.howtocopewithpain.org/blog/314/november-pain-blog-carnival-thankfulness/
Tuesday, November 25, 2008
But sometimes it's not that simple. What happens when you laugh at a video of someone falling off a ladder, or find yourself straining to avoid hysterics when a home video shows a son hitting a line drive into his father's groin?
All of this points to a simple conclusion: Pain makes us laugh.
The ancient Greeks knew it, 17th century philosopher Thomas Hobbes knew it when he wrote "Leviathan," Chevy Chase knew it when he made a name for himself portraying a bumbling version of President Gerald Ford, and Johnny Knoxville knew it when he turned self-injury into a successful MTV television show called "Jackass."
Pain isn't supposed to be funny, yet it is a staple of humor and prompts laughter from audiences.
"There's sort of a universal element to slapstick," explained Diana Mahony, a psychologist and humor researcher with Brigham Young University and the author of "God Made Us to Laugh."
But she draws a distinction between the slapstick of Bugs Bunny or "Saturday Night Live" and laughing at a painful video shown on YouTube or "America's Funniest Home Videos."
"There's a lot of aggression and ill will in certain types of humor," said Mahony, noting that, despite humor's positive connotation, it isn't always beneficial. "The stuff that's going on right now, I think, is just a reflection of some of the negative aspects of human nature."
She points to theories from ancient Greece and Hobbes to explain why some find pain funny -- because it can make the person laughing feel greater than the object of his or her derision.
Mahony explained the mindset as, "I laugh in triumph and superiority at the foibles and stupidity of other people."
One example of this is the Darwin Awards, a Web site that recounts the exploits of people (a few of the stories are real) who, through poor decision-making or a seeming lack of common sense, remove themselves from the gene pool.
But Mahony notes that if your own relative or friend made a mistake that put them on the list, you would likely search for a way to justify their actions.
Another possible explanation for the humor is the detachment most people feel from the person injured on TV or in an Internet video. In addition to a person they probably don't know personally, the detachment can stem from the situation where the person gets hurt, which is often somewhat outlandish -- like an absurd skateboarding stunt.
"Whatever pain we see is just one component of what is otherwise a funny circumstance," explained Dr. Emanuel Maidenberg, a psychiatrist at UCLA Medical School.
The context, he said, delivers a mood of humor, which can prompt the audience to follow suit.
He noted that while people may laugh, the person being hurt is typically pained by something they chose to do. Television shows in the United States do not broadcast torture, he noted, a different situation where a person who found it humorous could very well have a deeper psychological issue.
Laughter: It's Not Just for Funny Stuff
While plenty of people laugh at situations that are not supposed to be humorous -- during a moment of silence, for example -- our laughing at them doesn't necessarily mean we find it funny.
"The common misconception about laughter is that laughter is, for the most part, a response to humor," Mahony said.
Instead, she explained, laugher is activated like a steam gauge, where a buildup of feelings prompts an outburst.
"It's nature's way of letting out tension or a buildup of emotions," she said.
Comedian David Alan Grier characterizes it similarly.
"When your boyfriend, your girlfriend dumps you, you're grieving. It builds and builds and it gets to a fever pitch, it's like a boil that's got to be lanced. It's a human need. It's a human emotion. It's the human condition," he said.
Maidenberg noted that some people might also cry rather than laugh because they are taught to suppress tears.
"They may adapt a replacement of laughing instead of showing pain," he said.
While laughter is typically an acceptable expression, some cultures and subcultures frown upon crying, which is physiologically similar.
The Best Medicine?
In the past 30 years, laughter has been promoted as a cure-all for ailments, the idea being that a laughing patient will heal faster or be able to overcome more.
The idea gained momentum when the journalist Norman Cousins wrote about his experiences as a patient, where laughter may have helped heal him, in the New England Journal of Medicine in 1976.
But while laughter may have benefits and put a patient in a relaxed state, it may have gotten too much credit.
"Laughter is good, but it's not the only game in town," Mahony said.
One of the primary benefits of laughter, she explained, is that it distracts, something that can be done with a horror movie or a tear-jerker just as well -- and possibly better -- than with a comedy.
In the original article, Cousins himself admitted that his recovery from a supposedly incurable illness might have happened on its own -- without laughter or medical treatment.
So, while laughter may have benefits, so can other emotions -- as long as the person wants to take them in.
And what entertains us can't fully be explained by science -- it's a matter of taste.
"Sense of humor is truly the fingerprint of personality," Mahony said..
Sunday, November 23, 2008
The topic for this forum was "Assessing Pediatric Pain: Current Evidence and Practice". As usual, we had a distinguished international faculty, lots of discussion, a beautiful location, good food and entertainment, and the opportunity to discuss important scientific and clinical issues of children's pain. The topics and faculty for the meeting are listed below.
When available, links to presentation slides by clicking on presenters' names:
- Assessing Pain by Self Report: Carl von Baeyer, Saskatoon, SK, Canada
- Assessing Pain with Behavioural Measures: Ron Blount, Athens, GA, USA
- Assessing Pain by Facial Expression: Ken Prkachin, Prince George, BC, Canada
- Pain Assessment in Infants: Rebecca Pillai Riddell, Toronto, ON, Canada
- Pain Assessment in Children with Cognitive Impairment: Lynn Breau, Halifax, NS, Canada
- Assessment of Chronic Pain: Tonya Palermo, Portland, OR, USA
- Using Technology to Assess Pain: Jennifer Stinson, Toronto, ON, Canada
- Putting Pain Assessment into Practice: Linda Franck, London, UK
- Cultural Issues in Pain Assessment: Allen Finley, Halifax, NS, Canada
A survey of patients regarding the care they received during a hospitalization shows most are satisfied with their experience. Many patients, however, gave low scores to hospitals on pain management and discharge instructions.
Hospitals are routinely assessed for their quality of care based on outcome data. But there has been little information on how patients feel about their care. The study, published today in the New England Journal of Medicine, came from the Hospital Consumer Assessment of Healthcare Providers and Systems survey. The survey of 2,400 hospitals targeted six areas: communication with doctors, communication with nurses, communication about medications, quality of nursing services, how well hospitals prepared patients for discharge, and pain management.
On average, about 67% of patients said they would definitely recommend the hospital in which they were treated. The study found that hospitals with higher nurse-to-patient ratios had more satisfied patients. Moreover, the hospitals that tended to score higher on standard quality measures based on outcome data also tended to have more satisfied patients. "There need be no trade off between ensuring that care is technically superb and addressing the needs of the patients," said senior author Arnold Epstein, chairman of the Department of Health Policy and Management at Harvard School of Public Health.
There was some regional variation, with patients in Birmingham, Ala., giving hospitals the highest marks and patients in East Long Island, N.Y., the lowest marks. The most consistent complaint among all patients was in pain management, where nearly one-third did not give high ratings. About one-fifth of patients also said the hospital did not communicate discharge instructions well.
To view data on individual hospitals, go to the U.S. Department of Health & Human Services Hospital Compare website and click on the "Find and Compare Hospitals."
Wednesday, November 19, 2008
By Steven Reinberg
By Steven Reinberg
Gulf War illness, dismissed by some as a psychosomatic disorder, is a very real illness that affects at least 25 percent of the 700,000 U.S. veterans who took part in the 1991 Gulf War.
Its likely cause was exposure to toxic chemicals that included pesticides that were often overused during the war, as well as a drug given to U.S. troops to protect them from nerve gas, a frequent weapon of choice of former Iraqi leader Saddam Hussein.
And no effective treatments have been devised for the disorder.
Those are three key conclusions of a Congressionally mandated landmark report released Monday by a federal panel of scientific experts and veterans.
"It is very clear that Gulf War illness is a real condition that was not caused by combat stress or other psychological factors," said Lea Steele, scientific director of the Research Advisory Committee on Gulf War Veterans' Illnesses, which issued the report, and an associate professor at Kansas State University.
"This is something we need to take seriously," Steele said. "These folks were injured in wartime service, much as people who were shot with bullets or hit with bombs."
The committee presented the 450-page report to Secretary of Veterans Affairs James Peake.
Gulf War illness is frequently described as a collection of symptoms that includes memory and concentration problems, chronic headaches, fatigue and widespread pain. Other symptoms can include persistent digestive problems, respiratory symptoms and skin rashes.
The panel also said Gulf War veterans have much higher rates of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's Disease) than other veterans, and soldiers who were downwind from large-scale munitions demolitions in 1991 have died from brain cancer at twice the rate of other Gulf War veterans.
In reaching its conclusions, the panel reviewed evidence about a wide range of possible environmental exposures that could cause Gulf War illness. That review included hundreds of studies of Gulf War veterans, research in other groups of populations, animal studies of toxic exposures, and government investigations about events and exposures during the Gulf War, which began after Hussein invaded Kuwait.
Speculation about the causes of Gulf War illness has included exposure to depleted uranium munitions, vaccines, nerve agents and oil well fires.
The new report says the illness was caused by soldiers' exposure to certain chemicals, Steele said.
"When you put all the evidence together there are two chemicals that jump out as the main causes," she said. One is a drug called pyridostigmine bromide, which is a cholinesterase inhibitor that was given to the troops to protect them against nerve gas.
"It turns out that people who took those pills have a higher rate of Gulf War illness," Steele said. "And people who took more pills have even higher rates of Gulf War illness."
In addition, soldiers were exposed to pesticides that were also cholinesterase inhibitors, Steele said. "The strongest evidence points to pyridostigmine bromide and pesticides as causal factors," she said. "This type of illness has not been seen after other wars."
While pyridostigmine bromide is still in use, its use is more limited than it was in the first Gulf War. It's currently being used against one type of nerve agent, but is not being given out on a widespread basis, Steele said.
"The Gulf War was the only time a lot of people used this drug," she said.
Steele added that the U.S. military has also cut back on its use of pesticides since the 1991 war.
There are other factors that, while not likely causes of Gulf War illness, can't be ruled out, Steele said. These include exposure to nerve agents, exposure to smoke from oil well fires, and vaccines given to the troops. The panel ruled out depleted uranium and anthrax vaccine as causes.
The panel also found government research and funding into Gulf War illness wanting. "There has not been sufficient attention given to Gulf War illness. It's a real problem," Steele said.
"In recent years, both the Department of Defense and the Department of Veterans Affairs have reported a lot of studies that weren't Gulf War illness as Gulf War research," Steele added. "Some of the money was misused."
The panel noted that overall federal funding for Gulf War research has declined substantially in recent years; the group urged lawmakers to devote $60 million annually to such programs.
When veterans with Gulf War illness go to Veterans Administration hospitals for treatment, their problems often aren't taken seriously, Steele said. "VA docs often know nothing about it and aren't able to help them. Sometimes they treat them as if they are head cases or malingering," she said.
James Binns is chairman of the U.S. Department of Veterans Affairs' Research Advisory Committee on Gulf War Veterans' Illnesses. "We have no treatments that work," said Binns, a Vietnam veteran and former Pentagon official. "I would like to see the new administration take this more seriously. When you look at all the studies, it's as clear as the nose on your face that this [Gulf War illness] is real." It took 20 years to admit that Agent Orange, a defoliant used in the Vietnam war, caused illness, Binns said. "It's now coming up to 17 years on Gulf War illness," he said. "Troop exposures [to these chemicals] were a serious but honest mistake. Covering it up rather than trying to help them has been unconscionable."
James Binns is chairman of the U.S. Department of Veterans Affairs' Research Advisory Committee on Gulf War Veterans' Illnesses.
"We have no treatments that work," said Binns, a Vietnam veteran and former Pentagon official. "I would like to see the new administration take this more seriously. When you look at all the studies, it's as clear as the nose on your face that this [Gulf War illness] is real."
It took 20 years to admit that Agent Orange, a defoliant used in the Vietnam war, caused illness, Binns said. "It's now coming up to 17 years on Gulf War illness," he said. "Troop exposures [to these chemicals] were a serious but honest mistake. Covering it up rather than trying to help them has been unconscionable."
Tuesday, November 18, 2008
Acupuncture: An Update
As a licensed acupuncturist, I am often asked by both medical professionals and laypersons whether acupuncture actually “works” and whether it should really be considered part of a belief system rather than science.
Fortunately, when responding to these questions, I am able to draw on a growing body of literature that supports the use of acupuncture for a variety of painful conditions. Nevertheless, there is still controversy about how it works and how to identify those patients who will most benefit from it.
Primarily because of difficulties in obtaining funding to perform substantive studies and in designing studies that accurately compare real and sham acupuncture, there are still a relatively limited number of well-designed, published studies on acupuncture. However, several recent studies, which I will describe next, do provide useful information on its potential benefits and mechanisms of action.
One of the questions that has perplexed researchers is how acupuncture can continue to provide benefits for long periods after the treatment is performed. A recent article has suggested a possible explanation for this phenomenon. Using functional MRI, Dhond and colleagues compared the resting-state brain activity of 15 healthy patients who received acupuncture that consisted of needling at a single traditional acupuncture point and sham acupuncture that involved simulated needling but no actual insertion.
The researchers found that, unlike sham therapy, acupuncture treatment produced multiple changes, including enhanced resting default mode network (DMN) connectivity with several areas of the brain, such as the anterior cingulate cortex, periaqueductal gray, amygdala, and hippocampus. The DMN is one of the resting state networks in the brain that is deactivated during the performance of a task. The authors theorized that these changes involved in a variety of functions, including memory and the perception of pain, may explain at least some of the lasting effects of acupuncture. This study also found evidence that acupuncture may induce changes in the sympathetic nervous system.
Issues in studies
The problems that are encountered in studying acupuncture are highlighted in 2 articles that sought to determine its efficacy based on earlier studies. Manheimer and colleagues performed a meta-analysis of studies on acupuncture for osteoarthritis of the knee. They were able to find only 11 studies that were randomized and controlled; 5 of those studies included 50 or fewer participants. Furthermore, there was a substantial degree of heterogeneity in results from study to study. Pooled results indicated that acupuncture was no more effective than sham acupuncture in decreasing pain in the short term or at 6-month follow-up. However, patients who received acupuncture had clinically relevant short- and long-term improvements compared with patients who received either treatment as usual or who were kept on a waiting list for treatment.
A significant problem identified by this meta-analysis was the variability as to what constituted sham acupuncture. Some studies used no needling; others employed needling at nontraditional points. This is important because it is still unclear whether needling the traditional points provides more analgesia.
Mayhew and Ernst performed a similar meta-analysis on studies of acupuncture to treat fibromyalgia. Only 5 studies fit their inclusion criteria, and all had 100 or fewer participants. These authors also found variable results. Three of the studies reported that acupuncture was beneficial while 2 reported negative results. However, in 1 of the negative studies, there was at least a short-term reduction in the number of tender points among patients who received acupuncture.
Because I virtually always use electrical stimulation when I perform acupuncture, I found one finding in this meta-analysis to be especially interesting. The 2 negative studies used traditional Chinese acupuncture, which consists of manual manipulation of the needles. In contrast, the 3 studies that found acupuncture to be beneficial employed electrical stimulation.
This stimulation appears to play a significant role in the effectiveness of acupuncture. Needles are usually inserted for 15 to 30 minutes during treatment, and the provision of a consistent level of stimulation during this period appears to be important. Obviously, it would be difficult if not impossible for a practitioner using manual manipulation to provide this over the course of a single treatment much less to provide anything close to consistency when treating multiple patients during the day.
Acupuncture for chronic pain
Several recent studies of large numbers of subjects indicate that acupuncture has beneficial effects for some of the most common pain conditions beyond those that are provided by standard treatments.
As I noted in a recent column (“Update on Treatment of Low Back Pain: Part 2,” Psychiatric Times, July 2008, page 13), the American Pain Society/American College of Physicians clinical practice guideline on chronic low back pain (CLBP) reported that there was a fair level of evidence for the use of acupuncture for this problem. A more recent observational study of 2564 patients with CLBP found that those who received acupuncture reported significantly diminished pain and number of days lost from work.
Witt and colleagues compared 1880 patients with chronic neck pain who received acupuncture with an equal number of controls. Those who received acupuncture and routine care had statistically significant improvements in both pain and disability status at 3-month follow-up compared with those in the control group who received only routine care.
Taken overall, these studies indicate that acupuncture continues to be a useful treatment but that more and better studies on both its clinical efficacy and underlying mechanisms of action are needed.
Acupuncture—an ancient healing practice that has shown promise in treating chronic pain—typically involves a period of active needle stimulation, followed by a longer period of rest. It appears that the analgesic (pain-relieving) effects of acupuncture may actually peak long after the active stimulation ends. In the first study of its kind, NCCAM-supported researchers from Massachusetts General Hospital, Logan College of Chiropractic, and Kyunghee University (Korea) evaluated the effects of acupuncture on brain activity following active stimulation.
The researchers used functional magnetic resonance imagery (fMRI) to monitor brain activity in 15 healthy adults before and after true acupuncture and sham acupuncture. The procedure lasted 150 seconds, and the rest period was 5.5 minutes. They also monitored heart rate and respiration and surveyed the subjects on their perception of pain and other sensations (such as deqi, unique sensations experienced in connection with acupuncture and considered to be signs of its effectiveness).
Analysis of the fMRI images showed that following true acupuncture—but not sham—there were increased connections among the parts of the brain involved in the perception and memory of pain. The subjects also reported stronger sensations with true acupuncture than with sham. The researchers conclude that acupuncture changes resting-state brain activity in ways that may account for its analgesic and other therapeutic effects.
- Dhond RP, Yeh C, Park K, et al. Acupuncture modulates resting state connectivity in default and sensorimotor brain networks. Pain. 2008;136(3):407–418.
Sunday, November 09, 2008
In Sickness and In Health offers a look at her own panic when pain flares in The Pain-Panic Syndrome.
Somebody Heal Me asks why it's so difficult to have an honest conversation about medication side effects in Topamax Troubles: Why Is It So Hard to be Honest About Side Effects?
The writer at Chronic Illness Pain Support is usually the helper, but writes in this post about her own challenge now when no one calls and no one offers to help. She's left Feeling a Touch Frustrated… and Lonely.
Fighting Fatigue describes her experience when an acquantance shared, unsolicited, his theory about her illness in Another Theory I Was Given About Fibromyalgia.
Being Chronically Ill is a Pill also writes about fear when her pain management regime changes in Rough Times Ahead.
Psychology of Pain alerts us to the danger of kids getting into adults' narcotics medications in Prescription Opiates and Kids: One Pill Can Kill.
Raingem: Migraine News, Commentary, and Opinions reviews the Effectiveness of Hypnosis in Headache and Migraine Treatment.
More about headache from SciTech Journal in Scientific Cause of Headache.
The Back Pain Blog writes about using heat to relieve back and neck pain in Declaring War on Neck Pain.
A Chronic Dose looks at the importance of the female vote when it comes to health care and why, with chronic disease such an integral part of health care policy and reform, we need to be educated and engaged voters. A must read: Women, Health Care and the Presidential Election: Why Our Vote Matters.
And IC Disease astounds us with a figure on healthcare costs in The Cost of Chronic Illness… another reason to educate ourselves about healthcare issues.
During exposure to a painful heat stimulus, depressed patients had decreased activity in the area of the brain responsible for pain modulation, Irina Strigo, Ph.D., of the University of California San Diego, and colleagues reported in the November issue of Archives of General Psychiatry.
When the same patients anticipated pain, they had increased activity in the right anterior insular region, dorsal anterior cingulate, and right amygdala, parts of an emotion-processing network.
"The anticipatory brain response may indicate hypervigilance to impending threat, which may lead to increased helplessness and maladaptive modulation during the experience of heat pain," the researchers said.
"This mechanism could in part explain the high comorbidity of pain and depression when these conditions become chronic," they said.
More than three-quarters of patients with depression have chronic pain and 30% to 60% of patients with chronic pain have depressive symptoms, according to the researchers.
But despite the overlap between the two conditions, they said, little is known about the neurobiological basis of how pain is processed in the brains of patients with major depressive disorder.
So they recruited 15 patients with major depressive disorder (12 females; mean age 24.5) and 15 healthy controls with no history of psychiatric disorders (10 females; mean age 24.3) to undergo functional magnetic resonance imaging before and during painful stimulation.
The depressed patients completed the Pain Catastrophizing Scale, which assesses magnification, rumination, and helplessness related to pain.
Both painful and non-painful levels of heat were applied to the participants' forearms as they viewed images that signaled the intensity of heat to come.
The temperatures did not differ significantly between the groups; the painful stimulus was 115.5° F in the depressed patients and 116.4° F for the controls (P=0.08), and the non-painful stimulus was 102.2° F for both groups (P=0.59).
Both groups reported similar subjective ratings of the unpleasantness and intensity of the painful heat.
The depressed patients rated the non-painful heat as significantly more unpleasant (P=0.04), "a finding that is consistent with our previous observations of the increased affective bias in major depressive disorder at non-painful temperatures," the researchers said.
During the anticipation of pain, the depressed patients had increased activation in the right anterior insular region, left anterior insular/inferior frontal gyrus, bilateral dorsal anterior cingulate cortex, right dorsolateral prefrontal cortex, several clusters in the left dorsolateral prefrontal cortex, clusters in the temporal and occipital lobes, and right amygdala.
The increased activity in the amygdala during anticipation was associated with greater levels of perceived helplessness toward pain (P=0.01) and rumination (P=0.02) in the depressed patients only.
During painful stimulation, the depressed patients had increased activity in the left parahippocampal gyrus and occipital cortex and the right amygdala, and decreased activity in the periaqueductal gray matter and the rostral anterior cingulate and prefrontal cortices.
The increased activity in the amygdala during painful stimulation was associated with perceived levels of helplessness (P=0.02) and rumination (P=0.03).
"These findings suggest that increased emotional reactivity during the anticipation of heat pain may lead to an impaired ability to modulate pain experience in major depressive disorder," the researchers said.
Cognitive models suggest that patients with major depressive disorder negatively bias their expectations, perceptions, and memories, which may lead to the development of passive coping styles that promote helplessness and the maintenance of depression, they said.
Past studies have shown that passive coping styles are associated with the enhanced emotional impact of chronic and experimental pain.
The current findings are in line with these models, the researchers said, and "may represent a neural correlate of hypervigilant monitoring of negative information in major depressive disorder," the researchers said.
The authors acknowledged that the study was limited by the "mixed sample of relatively modest size," and that the findings needed to be confirmed using more patients.
Bullies may actually enjoy the pain they cause others, a new study using brain scans suggests.
The part of the brain associated with reward lights up when an aggressive teen watches a video of someone hurting another person, but not when a non-aggressive youth watches the same clip, according to the University of Chicago study, published in the currentBiological Psychology.
"Aggressive adolescents showed a specific and very strong activation of the amygdala and ventral striatum (an area that responds to feeling rewarded) when watching pain inflicted on others, which suggested that they enjoyed watching pain," researcher Jean Decety, a professor in psychology and psychiatry at the University of Chicago, said in a university news release. "Unlike the control group, the youth with conduct disorder did not activate the area of the brain involved in self-regulation (the medial prefrontal cortex and the temporoparietal junction).
The study compared eight 16- to 18-year-old boys with an aggressive conduct disorder to a group that didn't show unusual signs of aggression. All participants underwent functional magnetic resonance imaging (fMRI) while watching videos in which people endured pain accidentally, such as when a heavy bowl was dropped on their hands, and intentionally, such as when a person stepped on another's foot.
Cynthia Toussaint was a ballerina. She was no stranger to the aches, pains and occasional injuries that came with the trade.
So when the pain from an injury to a right hamstring wouldn't subside, Toussaint, then 21, did what she could to endure it. After all, she had auditions to attend -- in particular, a promising role in the musical Fame.
When the burning, unrelenting pain was too much to bear, however, she sought a doctor's opinion.
"I was told that I wouldn't dance for eight weeks and I thought, 'No, they're wrong,'" she recalls.
But the pain would last for much longer than eight weeks. For months it persisted. A year and a half after the pain in her right leg started, she began to experience a similar pain in her left leg. Six and a half years after that, the pain had spread to both arms.
The spread of her condition was not always so gradual. One morning, she woke up to find that her left arm had bent itself into a state of permanent contracture.
"It was so shocking to wake up to find that one of my arms would not unfold anymore," she says.
Today the pain is everywhere. Toussaint describes it as a feeling as if she has "been doused with gasoline and lit on fire... burning from the inside out... It's pain like I never imagined."
The condition which ushered Toussaint into a life of chronic agony also gradually robbed her of her ability to dance, her ability to walk -- and, as it spread to her vocal cords, her ability to talk.
"Here I am 26 years later in a wheelchair," she says. "I had everything; my life was just starting. Suddenly I had this injury that never goes away."
Her voice would eventually return. But for years, Toussaint's battle with chronic pain and loss of function came spiked with the bitter reality that no matter how many doctors she saw, none could give her an accurate diagnosis of her condition.
Worse, without a solid diagnosis, she says many physicians refused to take her case seriously.
"I was told that I was crazy for 13 and a half years," Toussaint says. Once, one of her doctors told her to take a truth serum so she would admit that she was not truly in pain. Another suggested that she was fabricating her pain condition due to stage fright.
And a visit to yet another doctor was met with even greater insensitivity, she recalls.
"I said, 'What should I do?' and he said, 'Shoot yourself in the head.' He thought it was funny."
More than a decade had passed before Toussaint found that she suffered from a mysterious condition known as complex regional pain syndrome (CRPS), alternatively known as reflex sympathetic dystrophy syndrome (RSD). The nature of the condition continues to baffle doctors, as does its exact cause.
But finally, her pain had a name.
"When I got my diagnosis, it couldn't have been worse," Toussaint says. "But it was the happiest day of my life. They could never say I was crazy again."
Tuesday, November 04, 2008
Scientists have found clues in the brains of people with major depression that might help explain why so many depressed people also battle chronic pain, according to a U.S. study published on Monday.
Brain imaging showed people with depression had more activity in brain regions involved in emotions when they anticipated or experienced pain, the researchers found.
Irina Strigo of the University of California San Diego and colleagues told volunteers eight seconds beforehand that a painful experience was coming -- being touched on the arm with a device hot enough to cause brief pain but not injury.
"Not only do you really show this high activation of emotional areas when the pain was not there, but when the pain is there you see this helplessness, not even trying to modulate your experience," Strigo said in a telephone interview.
Her team tested 15 people in their mid-20s diagnosed with major depression but not taking medication to treat it. Their magnetic resonance imaging brain scans were compared to those of 15 similar people who did not have depression.
While anticipating the pain, the people with depression registered increased activation in brain circuitry involved in processing emotions, including structures called the amygdala and insula, compared with the people with no depression.
During the five seconds while their arm was touched with the hot device, their brains continued to show increased emotional activation. But at the same time, brain networks normally involved in mitigating pain were less activated in the depressed people than the others.
More than three quarters of depressed people have recurring or chronic pain, while 30 percent to 60 percent of people with chronic pain report symptoms of depression, the researchers wrote in the Archives of General Psychiatry.
"If a person has chronic pain together with depression, this is a very debilitating condition. This condition is very difficult to treat and the disability is much higher and the cost of treatment is very high," Strigo said.
She said the study's findings may point toward new ways to help patients, either through behavioral therapies or perhaps drugs.
Monday, November 03, 2008
Using single photon emission computed tomography (SPECT), researchers in France were able to detect functional abnormalities in certain regions in the brains of patients diagnosed with fibromyalgia, reinforcing the idea that symptoms of the disorder are related to a dysfunction in those parts of the brain where pain is processed.
"Fibromyalgia is frequently considered an 'invisible syndrome' since musculoskeletal imaging is negative," said Eric Guedj, M.D., and lead author of the study. "Past imaging studies of patients with the syndrome, however, have shown above-normal cerebral blood flow (brain perfusion) in some areas of the brain and below-normal in other areas. After performing whole-brain scans on the participants, we used a statistical analysis to study the relationship between functional activity in even the smallest area of the brain and various parameters related to pain, disability and anxiety/depression."
In the study, which was reported in the November issue of The Journal of Nuclear Medicine, 20 women diagnosed with fibromyalgia and 10 healthy women as a control group responded to questionnaires to determine levels of pain, disability, anxiety and depression. SPECT was then performed, and positive and negative correlations were determined.
The researchers confirmed that patients with the syndrome exhibited brain perfusion abnormalities in comparison to the healthy subjects. Further, these abnormalities were found to be directly correlated with the severity of the disease. An increase in perfusion (hyperperfusion) was found in that region of the brain known to discriminate pain intensity, and a decrease (hypoperfusion) was found within those areas thought to be involved in emotional responses to pain.
In the past, some researchers have thought that the pain reported by fibromyalgia patients was the result of depression rather than symptoms of a disorder. "Interestingly, we found that these functional abnormalities were independent of anxiety and depression status," Guedj said.