Laughter as a Form of Exercise - NYTimes.com

Is laughter a kind of exercise? That offbeat question is at the heart of a new study of laughing and pain that emphasizes how unexpectedly entwined our bodies and emotions can be.

For the study, which was published this year in Proceedings of the Royal Society B, researchers at Oxford University recruited a large group of undergraduate men and women.

They then set out to make their volunteers laugh.

Most of us probably think of laughter, if we think of it at all, as a response to something funny - as, in effect, an emotion.

But laughter is fundamentally a physical action. "Laughter involves the repeated, forceful exhalation of breath from the lungs," says Robin Dunbar, a professor of evolutionary psychology at Oxford, who led the study. "The muscles of the diaphragm have to work very hard." We've all heard the phrase "laugh until it hurts," he points out. That pain isn't metaphoric; prolonged laughing can be painful and exhausting.

Rather like a difficult workout.

But does laughter elicit a physiological response similar to that of exercise and, if so, what might that reveal about the nature of exertion?

To find out, Dr. Dunbar and his colleagues had their volunteers watch, both alone and as part of a group, a series of short videos that were either comic or dryly factual documentaries.

But first, the volunteers submitted to a test of their pain threshold, as determined by how long they could tolerate a tightening blood pressure cuff or a frozen cooling sleeve.

The decision to introduce pain into this otherwise fun-loving study stems from one of the more well-established effects of strenuous exercise: that it causes the body to release endorphins, or natural opiates. Endorphins are known "to play a crucial role in the management of pain," the study authors write, and, like other opiates, to induce a feeling of euphoric calm and well-being (they are believed to play a role in "runner's high").

It's difficult to study endorphin production directly, however, since much of the action takes place within the working brain and requires a lumbar puncture to monitor, Dr. Dunbar says. That is not a procedure volunteers willingly undergo, particularly in a study about laughing. Instead, he and his colleagues turned to pain thresholds, an indirect but generally accepted marker of endorphin production. If someone's pain threshold rises, he or she is presumed to be awash in the natural analgesics.

And in Dr. Dunbar's experiments, pain thresholds did go up after people watched the funny videos, but not after they viewed the factual documentaries.

The only difference between the two experiences was that in one, people laughed, a physical reaction that the scientists quantified with audio monitors. They could hear their volunteers belly-laughing. Their abdominal muscles were contracting. Their endorphin levels were increasing in response, and both their pain thresholds and their general sense of amiable enjoyment were on the rise.

In other words, it was the physical act of laughing, the contracting of muscles and resulting biochemical reactions, that prompted, at least in part, the pleasure of watching the comedy. Or, as Dr. Dunbar and his colleagues write, "the sense of heightened affect in this context probably derives from the way laughter triggers endorphin uptake."

The physical act of laughing contributed to the emotional response of finding something to be funny.

Why the interplay of endorphins and laughing should be of interest to those of us who exercise may not be immediately obvious. But as Dr. Dunbar points out, what happens during one type of physical exertion probably happens in others. Laughter is an intensely infectious activity. In this study, people laughed more readily and lustily when they watched the comic videos as a group than when they watched them individually, and their pain thresholds, concomitantly, rose higher after group viewing.

Something similar may happen when people exercise together, Dr. Dunbar says. In an experiment from 2009, he and his colleagues studied a group of elite Oxford rowers, asking them to work out either on isolated rowing machines, separated from one another in a gym, or on a machine that simulated full, synchronized crew rowing. In that case, the rowers were exerting themselves in synchrony, as a united group.

After they exercised together, the rowers' pain thresholds - and presumably their endorphin levels - were significantly higher than they had been at the start, but also higher than when they rowed alone.

"We don't know why synchrony has this effect, but it seems very strong," Dr. Dunbar says.

So if you typically run or bike alone, perhaps consider finding a partner. Your endorphin response might rise and, at least theoretically, render that unpleasant final hill a bit less daunting. Or if you prefer exercising alone, perhaps occasionally entertain yourself with a good joke.

But don't expect forced laughter to lend you an edge, Dr. Dunbar says. "Polite titters do not involve the repeated, uninhibited series of exhalations" that are needed to "drive the endorphin effect," he says. With laughter, as with exercise, it seems, there really is no gain without some element of pain.

http://well.blogs.nytimes.com/2012/10/24/laughter-as-a-form-of-exercise/?pagewanted=print

Listening without judgment an important component of pain management - The Clinical Advisor

For as long as I've been in the medical field, I've heard the phrase, "Pain is what the patient says it is." Nurses are taught to assess pain as the fifth vital sign, and have multiple ways to assess a pain level as accurately as possible, from number scales to pictures. But as providers, are we really listening when patients complain of pain?

Most of us have patients who always seem to be complaining about some ache or pain. There are those patients who keep coming back time and again with the same pain, despite our best efforts to help them. This can be frustrating for the patient and the provider. I know many providers who "tune out" when these patients start discussing their pain.

I've been thinking about people's perception of pain all week. I had some minor cartilage repair in my wrist that turned out to be a more extensive surgery than anticipated. I've had great pain control post-operatively, but it reminded me that this isn't always the case.

Seven years ago, I had laproscopic surgery and was in excruciating agony when I came out of anesthesia. I was reporting a 10 out of 10 on the pain scale during recovery, but the nurses just brushed me off, telling me that I had no pain tolerance and to go home and take my painkillers. "Don't tell a woman who has given birth without pain medication or an epidural that she has no pain tolerance," I thought.

Eighteen awful hours later I had a huge hematoma. It looked like a bikini bottom made from bruising. When I saw the surgeon, he was appalled that no one had called him about my unusual pain. If they had alerted him, he might have been able to stop the internal bleeding and prevent the hematoma from growing so large.

Managing pain is a huge part of my profession, and I see such extremes in the way people respond to pain. I've seen women roll onto the labor floor laughing and chatting. "Well, we know she's not in labor," says the nurse. And the nurse is right, most of the time. But every now and then we are wrong, and the mom is in active labor with advanced cervical dilatation.

More often we see the moaning, cursing, writhing women, not in active labor yet, but in obvious pain. The puzzle, as an obstetric provider, is how to best get her comfortable before active labor starts. Who am I to say that a patient's early labor pain isn't as intense as another's active labor pain? A patient's pain is what she says it is.

I also see many women complaining of chronic dysmenorrhea or dyspareunia, often complex and difficult to manage disorders. Typical pain management strategies can be ineffective for these women and they are often frustrated, having been written off by practitioners as hypochondriacs or drug seekers. Sometimes patients complaining of chronic pain are drug seeking, but isn't addiction a form of pain as well?

I try to keep listening when my patients tell my about their pain, then work on developing a plan with the patient to best meet their needs and get them out of pain as quickly as possible. This may include referral to a specialist or to pain management.

Pain can be debilitating and can be a cause, as well as an effect, of depression. In my experience, pain is usually a sign that something is wrong, somewhere. If we listen well, ignoring our own judgments and preconceived notions, we may actually be able help relieve the pain.

Robyn Carlisle, MSN, CNM, WHNP, works as a full-scope midwife at University Doctors and Kennedy University Hospital in Sewell, N.J.

http://www.clinicaladvisor.com/listening-without-judgment-an-important-component-of-pain-management/article/262909/

Practical Pain Management

Practical Pain Management is the most prominent pain journal for practicing pain specialists.

http://www.practicalpainmanagement.com/

Patients:

http://www.practicalpainmanagement.com/patients

Spinal Steroid Injections Have History of Trouble - NYTimes.com

Perry D. Clark says that a steroid injected near his spine to relieve persistent back pain instead left him "way, way worse." Twelve years later, he still suffers from continuous stinging in his legs and feet and occasional bursts of excruciating pain.

"It's like somebody took a hot poker out of a fire and jammed it into my foot for two or three seconds," said Mr. Clark, a retired media professional from Petoskey, Mich.

The outbreak of fungal meningitis that has killed 14 people and sickened 156 more has focused attention on the risk of infection from spinal injections. But the same injections have also long been linked to other rare but devastating complications, including nerve damage, paralysis and strokes.

The Food and Drug Administration is already reviewing how to reduce the risk of "catastrophic neurological injuries" from the injections, said Dr. James P. Rathmell, chief of pain medicine at Massachusetts General Hospital, who is involved in the review. The risk of infections did not even factor into the review, though it will now, he said.

The meningitis outbreak is raising new questions about the steroid spinal injections, which are given to millions of Americans. Use has mushroomed even as clinical trials have found only modest evidence that the injections help. Moreover, the steroids, while approved for uses like relieving inflammation in joints, have not been approved by the F.D.A. for epidural injections, next to the spinal cord.

"Not only were these people killed, but there was no ethical reason to give this treatment," said Dr. William Landau, a professor of neurology at Washington University in St. Louis, referring to those who died of meningitis.

Many pain specialists dispute that conclusion. Doctors are allowed to, and often do, prescribe drugs for unapproved uses, they say, and steroids have been used to treat back pain for decades. They contend the injections can be less risky than narcotics or surgery.

Even Dr. Rathmell, who has been calling attention to the complications, said they occur in only about one in 10,000 cases. "In the right individuals, they are a tremendous help," he said of the injections.

Kenny Alhadeff, the producer of the Broadway musical "Memphis," says he is one of them. Several years ago, he said, he had such severe back pain that "I could barely get into a car." His first injection brought immediate relief. Now, after a few years of periodic injections, he is pain-free.

But some defenders of the practice concede that injections are overused. They are most useful for people with herniated disks and pain radiating into the legs or arms. But a study published in the journal Spine in 2007 found that fewer than half of the injections given were for these conditions.

"We are doing too many of these, and many of those don't meet the proper criteria," said Dr. Laxmaiah Manchikanti, who runs a pain clinic in Paducah, Ky., and is chairman of the American Society of Interventional Pain Physicians. He also said that about 20 percent of doctors who perform the procedures were not adequately trained.

Dr. Manchikanti said his own review of Medicare records found an increase of nearly 160 percent in the number of injections from 2000 to 2010.

The increased use is driven by the aging of the population, the desperation of patients and the desire of physicians to help — and there are financial incentives. Medicare and private insurers pay $100 to several hundred dollars for an injection, and there are pain clinics that do almost nothing but injections.

Dr. Richard Deyo, a professor of family medicine at Oregon Health and Science University, said that despite the increase in injections and other aggressive treatments, surveys and Social Security disability records suggest that "people with back pain are reporting more functional limitations and work limitation, rather than less."

Evidence on the effectiveness varies by the condition being treated, the drug used and the injection technique.

A review last year by Washington State, which was considering whether to pay for such procedures, found that for one set of circumstances, there were seven clinical trials that showed the injections were helpful, another seven that found them no better or even worse than a placebo, and three with unclear results.

The state agency decided that the evidence was strong enough to justify paying for injections under certain circumstances.

The serious complications, while extremely rare, are more noticeable because of the explosive growth in the number of injections. In one anonymous survey, 287 pain physicians reported 78 serious complications, including 13 deaths, among their patients.

The injections are made into the epidural space just outside the spinal column. This is the same site used in numbing the pain of childbirth, though women in labor receive an infusion of a local anesthetic, not an injection of a steroid.

But the needle can sometimes go astray, putting the drug into the spinal fluid or arteries, causing nerve damage, hemorrhages and death to nerves by depriving them of oxygen. Many doctors use imaging and fluorescent dye to position the needle, but even that technique is not foolproof.

Another complication is arachnoiditis, an inflammation of a membrane surrounding the nerves of the spinal cord that is marked by pain, nerve damage and bowel and bladder dysfunction. Mr. Clark who said he has this condition, uses a catheter to urinate.

The F.D.A. review is focusing on developing best practices for injection techniques with the aim of reducing the risk of injury.

Some doctors are turning to steroids that are free of preservatives, which may damage nerves, and particles, which may clog tiny blood vessels feeding the spinal cord.

But such products in general are not made by drug manufacturers, causing doctors to turn to compounding pharmacies, which are lightly regulated. One of them, the New England Compounding Center, supplied a contaminated drug — called methylprednisolone acetate — that is suspected of causing the fungal meningitis outbreak.

Moreover, the particle-free steroids may not provide lasting relief, said Dr. Christopher Gharibo, an associate professor of anesthesiology and orthopedics at New York University.

Last year, the label for the steroid Kenalog, made by Bristol-Myers Squibb, was changed to say that epidural injection was not recommended. But the label for Pfizer's Depo-Medrol, the brand name version of methylprednisolone acetate, does not have such a warning.

A Pfizer spokesman said the company did not condone the epidural use of Depo-Medrol.

Dennis J. Capolongo, who runs an advocacy group called the End Depo Now Campaign, says the lack of warning is inexplicable.

A former photojournalist in Washington, Mr. Capolongo said an epidural injection of Depo-Medrol to treat hip pain in 2001 inflamed his nerves, leaving him hospitalized for weeks and bedridden for two years. The pain, while no longer so intense, is not completely gone.

"There are nights I cry myself to bed," he said.

http://www.nytimes.com/2012/10/12/health/before-meningitis-outbreak-injections-tied-to-risks.html?nl=todaysheadlines&emc=edit_th_20121012&pagewanted=print

Are these the five most unpleasant sounds in everyday life? | guardian.co.uk

Scientists from Newcastle University have drawn up a league table of the least pleasant sounds we may encounter as part of everyday life – albeit a slightly old-fashioned life as the top five include the rasp of chalk on a blackboard.

Working with 13 volunteers, they tested reactions to 74 different noises both in outward response and more closely via small changes in the brain.

The results are published in the latest issue of the Journal of Neuroscience and show, among other things, that acoustically anything in the frequency range of around 2,000 to 5,000 Hz was found to be unpleasant. The author of the paper, Dr Sukhbinder Kumar, is not surprised. He says:

This is the frequency range where our ears are most sensitive. Although there's still much debate as to why our ears are most sensitive in this range, it does include sounds of screams which we find intrinsically unpleasant.

The study, funded by the Wellcome Trust, took place at the trust's Centre for Neuroimaging at University College, London, using functional magnetic resonance imaging to watch how the volunteers' brains responded to the noises. These varied from the sound of a knife on a bottle – which emerged as the most unpleasant – to babbling water, which went down best.

The imaging showed a pattern in the connections between the region of the brain that processes sound, the auditory cortex, and the amygdala, which is active in the processing of negative emotions when we hear unpleasant sounds. The paper shows how in reaction to these, the amygdala modulates the response of the auditory cortex heightening activity and provoking our negative reaction.

Dr Kumar says:

It appears there is something very primitive kicking in.IIt's a possible distress signal from the amygdala to the auditory cortex.

The leader of the study, Professor Tim Griffiths from NewcastleUniversity, says that better understanding of the brain's reaction to sound could help in the study of medical conditions where sensitivity to noise plays a part. He says:

Shedding new light on the interaction of the amygdala and the auditory cortex might be a new inroad into emotional disorders and disorders like tinnitus and migraine in which there seems to be heightened perception of the unpleasant aspects of sounds.

Would you like to test your own reactions? Here you go, with the five least pleasant sounds from the study.

 
First, here's the knife on a bottle

Next, a fork on a glass

Now for us older ones, chalk on a blackboard
 

A ruler on a bottle, which most be the most unusual of the Worst Five

And finally nails on a blackboard

And that's it. As they say nowadays, Enjoy, although that isn't the right word.

http://www.guardian.co.uk/uk/the-northerner/2012/oct/10/newcastle-university-scientists-brain-unpleasant-sounds-reaction?newsfeed=true

Contaminated drug draws attention to steroid injection procedure Physicians divided on value of low-back steroid injections - The Boston Globe

The discovery that a potentially tainted drug is linked to 119 cases of meningitis nationwide has fueled debate among doctors about widespread use of the back-pain treatment, which has little proven longterm benefit.

Use of the medication, a ­steroid injected near the spine to quell inflammation, has ­increased in part because of the demands of an aging population and the relatively few risks associated with the injections when compared with surgery and other treatments, which ­also carry no guarantee of success.

Patients and doctors often saw a so-called lumbar injection as a safe alternative, until the outbreak of fungal meningitis cases tentatively linked to the injectable steroid supplied by a compounding pharmacy in Framingham.

"What one can say from 10,000 feet is that these are one of the most overused procedures in the United States," said Dr. Steven J. Atlas, a primary care internist and director of Primary Care Research & Quality Improvement Network at Massachusetts General Hospital. "I think it reflects the fact that treatments for low back pain and low back pain conditions often don't provide the ­relief that patients are wanting or looking for, and they in desperation or hope look to procedures that may offer them the magic cure."

A 2007 study in the medical journal Spine found that there was a greater than 200 percent increase in steroid injections administered for back pain in two different ways between 1994 and 2001. It concluded that fewer than half were performed for medical problems for which there was the strongest evidence they worked.

The steroid drug, methylprednisolone acetate, is not approved by the US Food and Drug Adminstration for use in epidural injections for back pain, but physicians are ­allowed to use drugs "off-label" for unapproved uses.

Critics of the injections say that patients overestimate the benefit they will receive from a treatment, and the injections are often used to treat ailments other than those most likely to respond to the steroid treatment. But proponents say that subgroups of patients can benefit from the injections.

Dr. Ray Baker, president of the International Spine Intervention Society, said word of mouth, not just the aging population, has probably helped drive the increase in injections. His analysis of Medicare data found almost 2.5 million injections in that patient population in 2011, and he estimated that they probably make up about half of injections administered last year in the United States.

"The vast majority of practitioners are trying to very conscientiously use these injections on their patients to increase their activities and functions," Baker said. "We have a pretty expectant population; we have a population of baby boomers that are not aging in a wheelchair or in a rocking chair. These are people that are playing tennis and golf and running into their 80s."

The Cochrane Review, an ­organization that analyzes the strength of medical evidence, published a review in 2010 of 18 randomized trials. Just two of the studies were deemed to show benefits greater than possible harm. The ­review concluded that there was not strong evidence for or against the use of the treatments. The review added it could not rule out the possibility some groups of patients would benefit.

"I would say that there does seem to be consensus that at least in well-selected patients with . . . spinal pain that ­involves nerve dysfunction or nerve root dysfunction, that they at least provide some benefit and the controversy revolves about how much benefit and the duration of benefit," said Dr. Steven P. Cohen, a professor of anesthesiology at Johns ­Hopkins School of Medicine.

For patients, the matter can be more clear-cut. Josephine Kendall, an 80-year-old from Methuen, said her lower back pain had gotten so bad that she could only lie down. She has to go to dialysis three days a week, and tasks as simple as bringing home groceries had become unbearable.

Two and a half years ago, she began receiving injections at New England Baptist Hospital, which she said transformed her life, for three months at a time.

When she heard the news about the possibly tainted drugs, Kendall asked her physician whether she was receiving injections supplied by the same company. She was not, and she said it has not changed her mind at all about whether to continue receiving injections.

"I can't exist without them; let's put it that way," she said.

Physicians said they had been inundated with calls from patients wondering if they had received the drug from New England Compounding Center. Some said that patients who were eligible for an injection were forgoing the procedure now.

Dr. Carol Hartigan, a physiatrist at the spine center at New England Baptist, said Tuesday that more than one patient she had seen who was a candidate for an injection has declined to receive it for now.

She noted that while anecdotally, individual patients can report dramatic improvement, it is crucial to evaluate the effectiveness of an injection and that she looks for at least a 50 percent improvement that lasts three months.

"Clinicians and patients can really exaggerate the response out of hope, Hartigan said. "So many people we see come in with this list and litany of injections they've had," and they still aren't fixed, she said. "We want the quick fix sometimes."

http://www.bostonglobe.com/lifestyle/health-wellness/2012/10/09/contaminated-drug-draws-attention-steroid-injection-procedure-physicians-divided-value-low-back-steroid-injections/1cQdfBP0dVidlJxNz2HogL/story.html?p1=Well_BG_Links

Some 13,000 May Have Gotten Meningitis-Linked Drug - WSJ.com

An estimated 13,000 patients may have been exposed to the tainted spinal steroid injections which have sickened more than 100 people with fungal meningitis and killed eight, federal officials said Monday, as clinics and surgery centers continued to reach out to those who could be affected.

It was the first estimate of the potential scope of the meningitis outbreak, which has been traced by federal and state investigators to three lots of methylprednisolone acetate injections produced by New England Compounding Center. Some 105 people in nine states have been sickened by fungal meningitis, said Curtis Allen, a spokesman for the Centers for Disease Control and Prevention.

Tennessee, Virginia, Indiana, Maryland and Michigan reported new cases. Tennessee—with 35 cases, the most of any state—also reported an additional death, its fourth, according to the CDC.

Investigators from the U.S. Food and Drug Administration and state officials are probing the Framingham, Mass., facility where NECC made the 17,676 potentially tainted steroid injections, which were then shipped to 75 clinics in 23 states, according to federal and state officials.

A CDC spokesman said it isn't possible to know how many cases there will be. The CDC and state health officials scrambled last week and over the weekend to track down patients who received the shots to see if they had been sick and to warn them to watch for possible symptoms.

The numbers of cases are rising sharply now not necessarily because people are continuing to get sick, but because investigators are pinpointing more illnesses among those who already received the injections of methylprednisolone acetate for relief of back and neck pain.

The injections were given between July and September. So far, those who have been infected developed symptoms between one and four weeks after receiving their injections.

"There's no evidence that new infections are occurring at a more rapid rate," said John Jernigan, medical epidemiologist at the CDC who is involved in the investigation.

It is too early to know how many people ultimately will be affected. Federal and state investigators must determine how many people received potentially contaminated injections, then track down each one. They must then confirm that those who have subsequently become ill actually had fungal meningitis and not another disease. There are "too many variables to speculate on the number of possible cases," said a CDC spokesman.

The FDA had already advised medical professionals last week not to use NECC-made products.The compounding pharmacy that produced the injections in question issued a recall Saturday of all products made at its compounding center. "This action is being taken out of an abundance of caution due to the potential risk of contamination," NECC said in a statement. The company has said it is cooperating with investigators.

Meningitis is a potentially deadly inflammation of the brain or central nervous system. It is usually caused by viruses or bacteria, but can also be brought on by fungi. The two fungi found thus far in some patients—known as aspergillus and exserohilum—are commonly found in the air and soil.

The fungal form of meningitis is particularly difficult to diagnose because the symptoms can be vague and mild initially, including fever, headache, nausea and stiffness of the neck, according to the CDC. People with fungal meningitis can also experience dizziness and confusion. Several of the patients in the current outbreak have had strokes.

Most of the people who have been sickened had normal immune systems, Dr. Jernigan said, meaning they weren't at particular risk of infections. While the investigation into how patients became infected is ongoing, there is some evidence to suggest that the fungi in the medication penetrated the lining protecting the central nervous system after being injected epidurally, Dr. Jernigan said.

While the fungi aren't harmful in the environment, they can become deadly when they flourish in a medication and are then injected directly into a part of the body that should not have germs, Dr. Jernigan said.

Ms. Reed underwent an autopsy; the lawyer said he didn't yet know the results.One possible victim, 56-year-old Tennessee resident Diana Reed, died Wednesday; she got meningitis after receiving steroid injections, says a lawyer for her family. She had received the injections at a facility that has since been closed because of a meningitis outbreak, according to its Web site.

The outbreak has drawn renewed attention to the little-regulated world of compounding pharmacies. The FDA is hampered by federal law and conflicting federal court decisions over its authority to regulate compounding pharmacies. Current and former senior FDA officials said the agency has sought greater authority over the past decade, but so far has been stymied.

Government officials say the FDA is especially concerned about large compounding pharmacies that send out large amounts of drugs across the country—as opposed to a small pharmacy that may compound a medication three or four times a year.

In particular, the agency hasn't been able to take the normal steps it would take to ensure the safety of a drug produced at a compounding pharmacy. That includes requiring and evaluating clinical trials, and inspection of manufacturing facilities.

Attempts in the past by the agency to regulate more strenuously have been challenged in court.

http://online.wsj.com/article/SB10000872396390443982904578044682649925200.html?

The Mystery of Pain by Emily Dickinson

The Mystery of Pain

Pain has an element of blank;
It cannot recollect
When it began, or if there were
A day when it was not.

It has no future but itself,
Its infinite realms contain
Its past, enlightened to perceive
New periods of pain. 

Emily Dickinson

http://www.poemhunter.com/poem/the-mystery-of-pain/

Painkilling chemicals with no side effects found in black mamba venom | Not Exactly Rocket Science | Discover Magazine

The black mamba has a fearful reputation, and it's easy to see why. It can move at around 12.5 miles (20 kilometres) per hour, making it one of the world's fastest snakes, if not the fastest. Its body can reach 4.5 metres in length, and it can lift a third of that off the ground. That would give you an almost eye-level view of the disturbingly black mouth from which it gets its name. And inside that mouth, two short fangs deliver one of the most potent and fast-acting venoms of any land snake.

Combined with its reputation for aggression (at least when cornered) and you've got a big, intimidating, deadly, ornery serpent that can probably outrun you. It's not the most obvious place to go looking for painkillers.

But among the cocktail of chemicals in the black mamba's venom, Sylvie Diochot and Anne Baron from the CNRS have found a new class of molecules that can relieve pain as effectively as morphine, and without any toxic side effects. They've named them mambalgins.

Diochot and Baron started by searching animal venoms for chemicals that could block ASICs – not the shoe manufacturer, but a group of pain-inducing proteins called acid-sensing ion channels. They're like miniature gates, which dot the surface of neurons.

When we're injured, our damaged cells release an "inflammatory soup" of chemicals that triggers feelings of pain. Among the first of these harbingers are simple protons – positively charged particles that make the local tissues more acidic. The ASICs detect and respond to protons by opening up, allowing positive ions to flood inside, and causing the neurons to fire. They're warning systems that tell our bodies that something is wrong.

Diochot and Baron found two peptides (short proteins) from black mamba venom that block ASICs—mambalgin-1 and mambalgin-2. They act as padlocks that latch onto the closed proteins and stop them from opening, even when surrounded by protons. And they have characteristics that are almost too good to be true.

They work quickly and effectively against every type of ASIC found in our nervous system. As painkillers, they're as potent as morphine. They'll numb the sharp pain of a burn, as well as the dull throb of an inflamed limb. They're incredibly specific: they don't stop neurons from firing more generally, and they don't block any of the other gate-keeping proteins found in these cells. And unlike other similarly shaped proteins, they don't have any toxic effects, such as paralysis, convulsions or breathing difficulties. (The list of side effects that Diochot and Baron checked for, and saw no sign of, includes "death"; good to know.)

Animal venoms, of course, are better known for causing pain rather than dulling it. Many work through ASICs too. The Texas coral snake, for example, has venom that causes excruciating pain, thanks to a toxin called MitTx that makes ASICs much more sensitive to protons. The Trinidad chevron tarantula uses a different toxin that locks ASICs in their open state, allowing them to constantly trigger sensations of pain.

So why does the black mamba have potent painkillers in its arsenal? No one knows, but it's not alone. "Cobra venom, and more recently the corresponding purified cobrotoxin, have been used for instance for the control of pain in traditional Chinese medicine," says Baron. But cobrotoxin can also paralyse muscles; mambalgins, on the other hand, kill pain and little else.

The team is now exploring the properties of mambalgins even further. They're years away from turning these proteins into usable painkillers, but they've already been granted a patent, and found an industrial partner –a company called Theralpha that specializes in treatments for pain.

In the meantime, the mambalgins are already teaching us more about the basis of pain. In the central nervous system – the brain and spine –they mainly work by blocking a specific ASIC known as ASIC1a. If mice don't have this protein, mambalgins do nothing for them.

But it's a different story in the peripheral nervous system – the nerves that branch through the rest of our body. There, mambalgins are more than capable of relieving pain, even in mice that lack ASIC1a. That's because they work by blocking a different ASIC known as ASIC1b, whose role in pain has been unclear until now.

So, the black mamba has provided us with two leads in the quest for a better painkiller. Its venom has helped to identify proteins that could be targeted to soothe pain in the central and peripheral nervous systems, and it has given us two chemicals that could potentially do the job.

http://blogs.discovermagazine.com/notrocketscience/2012/10/03/painkilling-chemicals-with-no-side-effects-found-in-black-mamba-venom/

When a Drug Addict Isn't Ready to Accept Help - NYTimes.com

"I'm addicted to painkillers," J., a thickset construction worker, told me on a recent afternoon in the emergency room, his wife at his side.

Two years before, after months of pain, stiffness and swelling in his hands and neck, his primary physician had diagnosed rheumatoid arthritis and had prescribed three medications: two to slow the disease and one, oxycodone, for pain.

Bolstered by the painkiller, J. had felt more limber and energetic than he had in years. "I could finally keep up with the other guys," he told me. He worked harder, and his pain worsened. His primary physician increased the oxycodone dose.

Soon, J. was looking forward more to the buzz than to the relief the pills brought. He went to see two other physicians who, unaware that he was double-dipping, prescribed similar medications. When a co-worker offered to sell him painkillers directly, J.'s use spiraled out of control.

By the time I saw him, he was taking dozens of pills a day, often crushing and snorting them to speed the onset of his high. With remarkable candor, he described how the drugs had marred every facet of his life - from days of missed work to increasing debt, deteriorating health and marital strain.

But when I listed the treatment options that might help, J. shook his head, looked from me to his wife, and got up. "I'm all set," he said, holding up his hands.

Then he walked out of the room.

Despair fell on his wife's face. "Please," she said, grabbing my arm, "you can't let him leave."

She'd found him twice in the past week slumped on the bathroom floor, impossible to arouse. Though she'd called 911, both times the hospital released J. within hours after he came to and insisted the overdose was accidental. "I just know I'm going to come home one day to find him dead," she said.

She had good reason to worry. Prescription drug abuse is America's fastest-growing drug problem. Every 19 minutes, someone dies from a prescription drug overdose in the United States, triple the rate in 1990. And according to the Centers for Disease Control and Prevention, prescription painkillers (like oxycodone) are largely to blame. More people die from ingesting these drugs than from cocaine and heroin combined. Yet while I shared her concern, there was little I could do to force J. into treatment.

My hospital happens to be in Rhode Island, one of about a dozen states where compulsory treatment for someone like J. (that is, someone not under the purview of the criminal justice system) does not exist. Had J. been a resident of nearby Massachusetts - or from one of more than 20 other states that permit involuntary addiction treatment - I would have suggested his wife petition a judge to force him into care. Had we met in any of a dozen states, I could have hospitalized J. myself - against his will and for up to several days.

The requirements for involuntary substance treatment vary widely across the nation, from posing a serious danger to oneself, others or property, to impaired decision-making or even something as vague as losing control of oneself. States approach compulsory treatment for mental illness with far greater uniformity. All allow it, and almost all restrict it to instances in which a patient poses an immediate danger to himself or another.

This common standard stems from a series of federal court cases that set procedural and substantive requirements for mental health commitments. But involuntary commitment for addiction treatment, while certainly not new, has received considerably less judicial attention.

In a 1962 case, Robinson v. California, the Supreme Court held that while conviction solely for drug addiction was unconstitutional, "a state might establish a program of compulsory treatment for those addicted to narcotics." Many did, others didn't. The high court has yet to revisit the issue.

Another complicating factor is society's disagreement about what addiction really is: a disease, a moral failing or something in between. Many (often patients themselves) see drug abuse as purely a choice. Under this view, justifying the lost autonomy and expense to taxpayers that accompany mandated treatment becomes a hard sell.

Yet a large and ever-growing body of research paints a far more complicated picture of addiction.

The cognitive concepts that we typically associate with "willpower" - motivation, resolve and an ability to delay gratification, resist impulses and consider and choose among alternatives - arise from distinct neural pathways in the brain. The characteristic elements of drug abuse - craving, intoxication, dependency and withdrawal - correspond with disruptions in these circuits. A host of genetic or environmental factors serve to reinforce or mitigate these effects. These data underscore the powerful ways in which addiction constrains one's ability to resist.

The spotty existence of commitment laws for addiction has created something odd in medicine: a landscape where the standard of care differs dramatically from one place to the next. But change seems to be afoot. In March, Ohio passed a law authorizing substance-related commitments. Pennsylvania is considering a similar bill.

In July, Massachusetts extended its maximum period of addiction commitment from 30 days to 90 days, a move driven by the state's growing opioid abuse epidemic. In the same month, however, California terminated its commitment program for drug abuse.

These shifts come at a time when private insurers increasingly refuse to cover even brief inpatient stays for treatment of opioid abuse and as states grapple with dwindling resources. Still, while short periods of involuntary custody make intuitive sense - to provide protection until the effects of intoxication or withdrawal subside - surprisingly little evidence exists to suggest that a longer period of commitment will lead to abstinence or prevent the behavior that justified commitment in the first place. Science must guide the crafting of these laws, but for now the empirical jury is decidedly out.

As I watched the color drain from J.'s wife's face, I decided to speak with him again. Short of forcing him to stay, I knew what she wanted was for me to change J.'s mind.

He stood near the exit, arms folded, coat zipped. I waited next to him and for several moments said nothing. Then I wondered aloud whether he feared the physical pain that existed apart from his addiction. Without looking at me, he nodded.

"What if we can find a way to treat your pain and also bring an end to the hurt this is causing you and your family?" I asked. "Perhaps together we can help you get your life back."

J. paused to consider my offer. For an instant, his face softened.

Then, just as quickly, he jerked his head and was gone. His wife followed him out, in tears.

http://well.blogs.nytimes.com/2012/10/01/addicted-to-painkillers-but-not-ready-for-help/?ref=health&pagewanted=print

Inside "Ouch!" - Radiolab - Podcast

Pain is a fundamental part of life, and often a very lonely part. Doctors want to understand their patients' pain, and we all want to understand the suffering of our friends, relatives, or spouses. But pinning down another person's hurt is a slippery business. 

Is your relentless lower back pain more or less unbearable than my crushing headache? Problem is, pain is maddeningly subjective. In this short, producer Tim Howard introduces us to three attempts to put a number on pain in the hopes that we can truly understand the suffering of another.

We begin with entomologist Justin Schmidt's globe-trotting adventure to plot the relative nastiness of insect bites and stings. Then, Paula Michaels, a professor in the History of Medicine at the University of Iowa, brings us back to 1948, to a well-intentioned but ultimately misguided attempt to demystify the pain of childbirth. And we end with a very modern, very personal struggle for understanding as non-fiction writer Eula Biss tries to rate her own chronic pain.

http://www.radiolab.org/blogs/radiolab-blog/2012/aug/27/pain-scale/

World Pain Foundation — Blog and News

WPF was established to provide educational resources that inform patients, medical professionals and the general public about the latest clinical advances, management and treatment options for pain. WPF mission is to:

* Foster professional standards among pain specialist professionals and industry
* Provide for communication among all of those affected by pain, including the general public, medical professionals and interested parties in government, business, and education
* Provide for education through the development of resources, publishing of articles and books, professional papers, and the sponsoring of seminars and conferences
* Stimulate the continued research, and advocacy by providing a forum for the raising of new ideas and an effective mechanism for dialog on these issues

http://worldpainfoundation.org/blog

Study uncovers simple way of predicting severe pain following breast cancer surgery - University of Warwick

Women having surgery for breast cancer are up to three times more likely to have severe pain in the first week after surgery if they suffer from other painful conditions, such as arthritis, low back pain and migraine, according to a Cancer Research UK study published in the British Journal of Cancer.

Of the women surveyed, 41 per cent reported moderate to severe pain at rest, and 50 per cent on movement, one week after their surgery. Most patients having breast cancer surgery are discharged home by this time.　

Psychological state was also important, with women who felt more optimistic before their surgery found to suffer lower intensity pain in the week afterwards. While those who had more extensive surgery to remove their lymph nodes were prone to more severe pain in the week after surgery.

The findings could be used as a simple way of identifying before surgery which breast cancer patients might benefit from extra pain relief or support, according to the researchers, based at the Universities of Warwick, Aberdeen and Dundee.

Study leader Dr Julie Bruce, from the University of Warwick, said: "Women generally receive the same advice and treatment for pain relief following breast cancer surgery, but this study shows how factors such as a patient's psychological state and whether they have a prior history of chronic pain can really affect their recovery.

"Importantly, doctors may be able to use this as a way of identifying women who need more intensive pain relief immediately after surgery. These results are particularly important because research shows that severe pain in the first week after surgery can significantly delay recovery."

Three hundred and thirty-eight patients from across North Scotland took part in the study. Each patient was asked to fill out detailed questionnaires before surgery, asking about their general health, how they were feeling and whether they had any existing pain. A week after surgery, patients were contacted by a member of the research team and asked specific questions about the amount and type of any pain they were experiencing and whether they had taken pain killers.

Catherine Harkin, a GP from Edinburgh, was diagnosed with breast cancer six years ago, aged 49. Her cancer was discovered by chance after she had a mammogram to investigate a large benign cyst in her left breast, revealing a small 1cm tumour in the opposite breast. After several attempts at removing the tumour surgically, she opted to have a mastectomy with full breast reconstruction.

She remembers what it was like afterwards: "I'd been very against having a mastectomy, but in some ways it was a relief because it meant an end to the rollercoaster of having lumps removed and then waiting for the results. In total I spent five days in hospital, after which I was given anti-inflammatory drugs and sent home. The drugs really helped with the pain, but it was a long time before I felt myself again and that's something that no one can really prepare you for."

"For me the worst part was not feeling in control of my pain, so it's really interesting to hear about research into ways of finding out in advance which women are likely to need extra help to recover from their surgery. I think this could really improve people's quality of life in the long term.

"I still suffer some after-effects from my surgery, but one of the real turning points for me was earlier this year, when I decided to join a local Dragon Boat paddling team set up especially for breast cancer survivors and their friends and family. It's great exercise and really helped me get my body confidence back and realise that, while I may not be as strong as I was, there are still lots of activities I can get involved in."

Liz Woolf, head of Cancer Research UK's information website, CancerHelp UK, said: "As well as being extremely important for a patient's comfort, post operative pain levels can have a significant impact on their treatment – for example it can increase risk of complications because they are unable to move as much as they should.　 It may also lead to them missing appointments, or being unable to carry out important postoperative exercises which aid their recovery. This is why it's so important to be able to identify in advance those who may be in need of extra pain relief or support.

"Earlier studies suggest that up to half of women who undergo surgery for breast cancer may continue to suffer from pain for up to a year afterwards. This study is ongoing and it will be helpful to see what impact things like having a history of chronic pain and psychological state may have on longer term pain after surgery."

http://www2.warwick.ac.uk/newsandevents/pressreleases/study_uncovers_simple/