A Move Toward Sex Equality in Preclinical Research | Pain Research Forum

Women suffer from chronic pain conditions in far greater numbers than do men, and recent research suggests that the basic biology of men's and women's experiences of pain might differ. Yet the overwhelming majority of basic pain studies are performed on male animals and male-derived cells. That is set to change, at least for researchers funded by the US National Institutes of Health (NIH), with new NIH guidelines mandating equal representation of both sexes in preclinical research. NIH director Francis Collins and Janine Clayton, director of the NIH's Office of Research on Women's Health, Bethesda, US, outlined the new policy in a commentary published May 14 in Nature.

 

According to the commentary, "The NIH is now developing policies that require [grant] applicants to report their plans for the balance of male and female cells and animals in preclinical studies in all future applications, unless sex-specific inclusion is unwarranted," such as in research of diseases affecting only males or only females.

 

The move will surely benefit women in the long run, said Rebecca Craft, who studies sex differences in pain at Washington State University Pullman, US. "This [policy] is finally going to hold people's feet to the fire to test female [animals]," Craft told PRF.

 

Jeffrey Mogil at McGill University, Montreal, Canada, also praised the new policy, which he described as particularly relevant to pain research. "There are huge, striking sex differences in pain—big stuff, not just a little more or a little less of something," he said. "Robust evidence of sex differences is as good or better in pain than in any other field," Mogil told PRF.

 

Clinical study design has undergone a revolution over the past 20 years, since the NIH began requiring equal numbers of women and men in nationally funded clinical trials. For decades, women took prescription drugs that were tested solely in men. In some cases, that practice led to unforeseen side effects and risks for women from medications. Although the transformation to gender-balanced trials took years to implement, researchers today hail it as a great achievement in medicine.

 

Now the NIH has taken the next step toward gender equality in science by requiring equal sex representation in animal experiments, and in work done with cells. The change is particularly important to pain researchers, said Craft, considering that "a number of pain syndromes are much more common in women." Without testing female animals, she added, "you are really not modeling the phenomenon very well."

 

Mogil echoed that sentiment. Whether or not there are sex differences that affect pain on a cellular level, "there are sex differences in the circuitry, and that is all you need to have the biology be robustly and fundamentally different between males and females," Mogil said.

 

The news has some researchers worried that the change might come with high costs, but Mogil said that fear is unfounded. "There is no downside and no tradeoff. We have everything to gain and very little to lose at all," he told PRF.

For example, if twice the animals will be required, that could double the price of breeding, housing, and tracking the animals. But Mogil doubts the new decree will drastically change research costs. "If you're using 12 animals, for example, you just use six male and six female," Mogil said, and track the data separately, "and combine again if there are no sex differences."

 

"I don't think six animals per sex is enough," to reveal subtle sex differences, Craft said, but then, that is not the purpose of the policy. "This is definitely a start. What we need to know most is when there are big differences … which would leap out at you, even with that small sample size."

 

The new rule could affect the progress of target validation and drug development. "For agents based on mechanisms determined from experiments performed on males, there is the possibility the biology is less relevant to females," said Mogil.

 

Researchers have stayed stuck in the rut of studying predominantly male animals and cells mostly out of convention. A single sex animal pool, researchers reasoned, would yield more reproducible results. And until recently, clinical trials overwhelmingly tested drugs on men, so it made sense to stick with male animals at the preclinical stage. "Until funders or journals start requiring it, no one is going to change," Craft said. The new guidelines will provide that push, she added.

 

A popular misconception also contributed to the historical male dominance, Mogil said. "People resisted before because they thought that data would be more variable in females." But as he demonstrated years ago (Mogil and Chanda, 2005), "that idea is empirically false. If anything, there is more variability in males. So what people were worried about all this time turns out to be wrong."

 

For researchers daunted by the thought of embarking on a new experimental paradigm built around equal representation of male and female animals, Craft suggests two papers for guidance (Greenspan et al., 2007Becker et al., 2005), and the NIH will reportedly provide training materials as part of the rollout of the new policy. The change will mean more work for researchers unfamiliar with female biology, Craft said, but that will be a worthy investment indeed.

 

Stephani Sutherland, PhD, is a neuroscientist, yogi, and freelance writer in Southern California, US.


Grand Unified Theory of Female Pain by Leslie Jamison | VQR Online

http://www.vqronline.org/essays-articles/2014/04/grand-unified-theory-female-pain

‘The Empathy Exams,’ by Leslie Jamison - NYTimes.com

Regarding the pain of others requires more than just a pair of eyes. It necessitates an act of the imagination: a willingness to think or feel oneself into the interior of another's experience, to cross between what Susan Sontag once designated as the kingdoms of the sick and of the well. This kind of empathetic border crossing can be both difficult and dangerous, the sort of journey of which one might say: "I get across quickly because I'm headed in the right direction, by which I mean the wrong direction. I'm going where no one wants to stay."

This statement, actually describing a trip into Mexico, serves as a manifesto for "The Empathy Exams," Leslie Jamison's extraordinary and exacting collection of essays. Jamison is a young writer and the author of a novel, "The Gin Closet." For the past few years she's been publishing a steady stream of intense, original essays, gathered here for the first time. Though they roam widely in topic and location, their collective preoccupation is with pain: what it means and what to do about it, both when it occurs in our own lives and when its location is far distant from us.

Jamison opens with her experience as an actor playing patients for medical students. "I'm called a standardized patient, which means I act toward the norms set for my disorders." Sometimes, working from a script, she plays a mother whose baby's lips are turning blue, and sometimes a young woman whose grief over her brother's death manifests as seizures. The students are assessed on how empathically they respond to her character's pain. Sensitive questioning elicits vital detail; clumsy handling causes the actor-patient to clam up.

"Empathy," she writes, "means realizing no trauma has discrete edges. Trauma bleeds. Out of wounds and across boundaries. Sadness becomes seizure. Empathy demands another kind of porousness in response." She means a porousness in the witness, a willingness to let a stranger's troubles seep in and slowly unfurl their meaning. But there is a porousness, too, in her style. Her intricate reconstruction of the empathy exams gives way to a more personal case history, an anatomization of two medical procedures she underwent in close succession: first an abortion and then heart surgery. In the essay's virtuosic close, she presents a script for Leslie Jamison: an intimate document, aestheticized but not anesthetized by the assumed tone, the medical dressing.

The damaged physical body, the gulf between sufferer and witness, this is Jamison's territory. Elsewhere, she turns her searching gaze on the community of people who suffer from the condition known as Morgellons, in which patients believe they're infested with hairs or fibers (an opportunity for some remarkable thinking about why patients prefer a diagnosis of physical infection to mental illness). She examines the culture around an ultramarathon in Tennessee, explores the case of the West Memphis Three, and considers poverty and violence in Los Angeles and Bolivia in a set of linked essays entitled "Pain Tours." In almost all of these pieces, her own pain: getting punched in the face in Nicaragua, having a worm emerge from her ankle after a trip to Bolivia, bad boyfriends and the wounding, witty lines they'd deliver.
 
This is an approach fraught with dangers, which necessitates walking an ethical tightrope between voyeurism and narcissism, between an unnatural interest in the woes of others and an unattractive obsession with the wounds of the self. It is to Jamison's credit that she doesn't choose the easy neutrality of the distanced observer, but rather voyages deeply into both extremes, maintaining almost always an admirable awareness about the perils of her approach.

Throughout, she pays close attention to the mechanisms of empathy, addressing not only its importance, as Rebecca Solnit did in last year's "The Faraway Nearby," but also its ethical complexities. In an essay that tacks brilliantly between a consideration of saccharine sentimentality and the artificial sweetener saccharin, she notes how sentimentality and anti-sentiment charm us by "coaxing out the vision of ourselves we'd most like to see," continuing: "If the saccharine offers some undiluted spell of feeling, . . . then perhaps its value lies in the process of emerging from its thrall: that sense of unmasking, that sense of guilt." This capacity for critical thinking, for a kind of cool skepticism that never gives way to the chilly blandishments of irony, is very rare. It's not surprising that Jamison is drawing comparisons to Sontag, clearly an influence on much of the thinking here. The struggle between irony and empathy surfaces again in two of the more troubling essays of the collection, a linked manifesto on the importance of accepting female woundedness as a subject worthy of attention. I can't say I much like the heavy-handed gender essentialism of her approach, or the moments of over-identification with her subjects, something her best essays rarely permit. On the subject of the plaster corsets Frida Kahlo wore to support her damaged spine, Jamison writes, "She would have given anything, perhaps, to have a body that rendered them irrelevant," adding that after Kahlo's leg was amputated, "she died the next year, as if this loss — after so many others — was what she finally couldn't bear." This is both histrionic and reductive. But it's a danger in keeping with her larger point, which is that it's worth risking an excess of feeling, rather than taking up the fashionable pose of world-weariness, which all too easily shades into detachment and then to cruelty.

Jamison is capable of the most extraordinary flourishes of image. On the case of the West Memphis Three, in which three teenagers were imprisoned for 17 years for the murder of three boys (wrongfully, many believe; they have since been freed), she writes: "Years ago witches were torched like fields. Their bodies held the controlled burn. Their bodies held evil like vessels so that evil would not be understood as something diffused across other bodies, across everyone." There is a glory to this kind of writing that derives as much from its ethical generosity, the palpable sense of stretch and reach, as it does from the lovely vividness of the language itself.

These are the essays of a working journalist. Most have been previously published in magazines like Vice, Harper's and Oxford American. Because they all work to some degree over the narrow field of personal experience, they inevitably turn up the same items of autobiography, perpetually introduced as if for the first time. This has a strange, unwitting effect in a book so preoccupied with the registering of and response to distress — it makes Jamison sound self-preoccupied, too caught up in her own stories to recognize that the reader has encountered them before. A small point, and clearly a consequence of the form, it makes one wonder a little hankeringly what this collection could have been if it had been worked just a touch more. But perhaps this is greedy. It's hard to imagine a stronger, more thoughtful voice emerging this year.

THE EMPATHY EXAMS
Essays
By Leslie Jamison
226 pp. Graywolf Press. $15.

Olivia Laing's latest book is "The Trip to Echo Spring: On Writers and Drinking."


Genetic Switches Turn Off Pain - Forbes

Researchers at King's College London have discovered a link between four common chronic pain syndromes (CPS), suggesting that some people may be genetically predisposed to suffer from conditions of this type. The study, published in the journal Pain, examined identical and non-identical twins and established that IBS, musculoskeletal pain, pelvic pain and dry eye disease may have hereditary links. Migraine was shown, as previously, to have a degree of genetic susceptibility but was not genetically linked to the other conditions.

Chronic pain syndromes such as irritable bowel syndrome (IBS) and chronic pelvic pain can severely affect someone's quality of life and their diagnosis relies on the presentation of symptoms, not on evidence of inflammation or other biomarkers on testing. These types of conditions are poorly defined and a challenge to healthcare providers because of their complex physiology, poor response to therapy and associated psychological elements. Chronic pain syndromes are more often reported in women than men.

The research team, funded by the Pain Research Foundation, studied more than 8,000 pairs of twins from the TwinsUK cohort using questionnaires asking about subjects' chronic pain symptoms. The sample compared groups of identical twins (sharing 100 per cent of their DNA) and non-identical twins (sharing 50 per cent of their DNA), with the differences between these two groups providing important information about the heritability of the conditions.

All of the CPS studied were more likely to be found in both twins in a identical pair than in the non-identical group, leading to the conclusion that each of the five syndromes are heritable. There was also a higher prevalence of CPS in females than males as expected.

Further analysis of different combinations of these CPS in female twin pairs showed that there were also stronger links between the syndromes in the identical group than in the non-identical group, indicative of a genetic link between four of the conditions (migraine was excluded from this second analysis). This suggests a common genetic pathway for CPS in general which was estimated to be 66 per cent heritable.

Dr Frances Williams, lead researcher from the Department of Twin Research at King's College London said: 'This study is one of the first to examine the role of genetic and environmental factors in explaining the links between different chronic pain syndromes. The findings have clearly suggested that CPS may be heritable within families. With further research, these findings could then lead to therapies which may change the lives of those suffering with chronic pain.'

The presence of a possible genetic predisposition to CPS is also supported by similarities in symptoms and could explain why many sufferers have more than one of these kinds of diseases. Shared symptoms such as fatigue, memory loss, sleep disturbance are often seen. Migraine was found less commonly with the other CPS so appears to be a different disease entity and was excluded from simultaneous analysis with the other syndromes.

Conditions such as these are often overlooked and not considered a research priority and so, as one of the first studies to examine the role of genetic and environmental factors in explaining possible links, these findings can now justify further study to find common genetic variants.

The overlap found between CPS found in this study is suggestive of an underlying genetic pathway, common for all CPS and could lead to more effective, targeted therapies in the future. This has the potential to significantly increase the quality of life for sufferers of conditions with chronic pain.



http://www.forbes.com/sites/paulrodgers/2014/02/06/genetic-switches-turn-off-pain/

Key genetic link between chronic pain conditions like IBS discovered - Kings College London

Researchers at King's College London have discovered a link between four common chronic pain syndromes (CPS), suggesting that some people may be genetically predisposed to suffer from conditions of this type. The study, published in the journal Pain, examined identical and non-identical twins and established that IBS, musculoskeletal pain, pelvic pain and dry eye disease may have hereditary links. Migraine was shown, as previously, to have a degree of genetic susceptibility but was not genetically linked to the other conditions.

Chronic pain syndromes such as irritable bowel syndrome (IBS) and chronic pelvic pain can severely affect someone's quality of life and their diagnosis relies on the presentation of symptoms, not on evidence of inflammation or other biomarkers on testing. These types of conditions are poorly defined and a challenge to healthcare providers because of their complex physiology, poor response to therapy and associated psychological elements. Chronic pain syndromes are more often reported in women than men.

The research team, funded by the Pain Research Foundation, studied more than 8,000 pairs of twins from the TwinsUK cohort using questionnaires asking about subjects' chronic pain symptoms. The sample compared groups of identical twins (sharing 100 per cent of their DNA) and non-identical twins (sharing 50 per cent of their DNA), with the differences between these two groups providing important information about the heritability of the conditions.

All of the CPS studied were more likely to be found in both twins in a identical pair than in the non-identical group, leading to the conclusion that each of the five syndromes are heritable. There was also a higher prevalence of CPS in females than males as expected.

Further analysis of different combinations of these CPS in female twin pairs showed that there were also stronger links between the syndromes in the identical group than in the non-identical group, indicative of a genetic link between four of the conditions (migraine was excluded from this second analysis). This suggests a common genetic pathway for CPS in general which was estimated to be 66 per cent heritable.

Dr Frances Williams, lead researcher from the Department of Twin Research at King's College London said: 'This study is one of the first to examine the role of genetic and environmental factors in explaining the links between different chronic pain syndromes. The findings have clearly suggested that CPS may be heritable within families. With further research, these findings could then lead to therapies which may change the lives of those suffering with chronic pain.'

The presence of a possible genetic predisposition to CPS is also supported by similarities in symptoms and could explain why many sufferers have more than one of these kinds of diseases. Shared symptoms such as fatigue, memory loss, sleep disturbance are often seen. Migraine was found less commonly with the other CPS so appears to be a different disease entity and was excluded from simultaneous analysis with the other syndromes.

Conditions such as these are often overlooked and not considered a research priority and so, as one of the first studies to examine the role of genetic and environmental factors in explaining possible links, these findings can now justify further study to find common genetic variants.

The overlap found between CPS found in this study is suggestive of an underlying genetic pathway, common for all CPS and could lead to more effective, targeted therapies in the future. This has the potential to significantly increase the quality of life for sufferers of conditions with chronic pain.



http://www.kcl.ac.uk/newsevents/news/newsrecords/2014/May/Key-genetic-link-between-chronic-pain-conditions-like-IBS-discovered.aspx

Doubts Raised About Off-Label Use of Subsys, a Strong Painkiller - NYTimes.com

Almost overnight, a powerful new painkiller has become a $100 million business and a hot Wall Street story.

But nearly as quickly, questions are emerging about how the drug is being sold, and to whom.

The drug, Subsys, is a form of fentanyl, a narcotic that is often used when painkillers like morphine fail to provide relief. The product was approved in 2012 for a relatively small number of people — cancer patients — but has since become an outsize moneymaker for the obscure company that makes it, Insys Therapeutics. In the last year, the company's sales have soared and its share price has jumped nearly 270 percent.

Behind that business success is an unusual marketing machine that may have pushed Subsys far beyond the use envisioned by the Food and Drug Administration. The F.D.A. approved Subsys only for cancer patients who are already using round-the-clock painkillers, and warned that it should be prescribed only by oncologists and pain specialists. But just 1 percent of prescriptions are written by oncologists, according to data provided by Symphony Health, which analyzes drug trends. About half of the prescriptions were written by pain specialists, and a wide range of doctors prescribed the rest, including general practice physicians, neurologists and even dentists and podiatrists.

More ...


Study examines back pain and depression in seniors - Senior's Health - Press of Atlantic City

Researchers at the Univ-ersity of Pittsburgh School of Medicine are studying the most effective means of treating chronic low back pain and symptoms of depression - together - in those 60 or older.

The ADAPT (Addressing Depression And Pain Together) study has been going on for four years. Seventy-five men and 123 women, ranging in age from 60 to 94, have taken part.

About a third of seniors suffer from low back pain. Nearly 20 percent of Americans age 65 and older have clinically significant symptoms of depression, according to the National Alliance on Mental Illness.

Up to 25 percent of seniors may suffer from both, said Dr. Jordan F. Karp, associate professor of psychiatry, the principal investigator.

"Chronic low back pain and depression make each other worse," Karp said. "Both can cause poor sleep, keep people from enjoying their usual activities, isolate them at home. Patients can enter a vicious cycle of the blues, pain, physical deconditioning and feeling hopeless."

Nearly 40 percent of those who've participated in the ADAPT study so far have had back surgery that has not worked, Karp said.

"People who are contemplating surgery need to have their depression treated, because depression can negatively affect outco-mes," he said.

About 30 percent of ADAPT participants to date have fibromyalgia, which may make it more difficult to treat depression.

Doctors aren't sure what causes fibromyalgia, and there is no cure for it, but there are treatments that ease the discomfort it causes.

About 12 million Americans - roughly 90 percent of them women - suffer from it.

People with fibromyalgia ache all over. Muscles may feel as if they've been overworked or pulled. Some patients may be very sensitive to touch and pressure. Other symptoms include fatigue, chronic headaches, trouble with concentration and memory, hypersensitivity to cold or heat, and tingling in extremities.

Although fibromyalgia is the second most common musculoskeletal disorder after osteoarthritis, the percentage of ADAPT participants who suffer from it is higher than he expected, Karp said. Only about 7 percent of older women have fibromyalgia, he said.

There are two phases to the ADAPT study.

In the first, which lasts six weeks, all participants take the anti-depressant drug venlafaxine (Efflexor).

About a third of those who've participated in the ADAPT study so far have shown improvement during phase one, Karp said.

In the second phase, which lasts 14 weeks, participants who haven't improved during the first phase are given a higher dose of venlafaxine and are divided into two groups.

Half receive the higher dose of venlafaxine only.

The other half also get counseling on how to manage pain, mood, sleep and other difficulties seniors who suffer from both conditions typically experience.

The purpose of phase two is to determine whether people who didn't improve during phase one need the problem-solving therapy to get them feeling better, or if the higher dose of venlafaxine will suffice.

"One of the reasons we picked the medicine we used is not only because the FDA approves it for depression, but it also has been observed to have analgesic (painkilling) effects," Karp said.

Low doses of venlafaxine increase levels of the neurotransmitter serotonin, which regulates mood. Higher doses of the drug also increase levels of the neurotransmitter norepinephrine, which may regulate both mood and pain.

Neurotransmitters are chemicals in the brain that relay signals between nerve cells to tell the brain what's going on in the body. Both serotonin and norepinephrine tend to block some pain messages.

When people are depressed, they tend to feel pain more acutely. Having less pain can relieve depression. Attacking both problems at once can produce a double benefit.

"Getting people moving and in better control of their pain through healthy behavior changes may also help their mood and improve quality of life," Karp said.

Zelienople, Pa., resident Robert Boykin, 73, a financial consultant with AXA, emphatically agrees. He's suffered from chronic back pain due to spinal stenosis.

"On top of that, back in November, I went into a real tailspin of depression," Boykin said. Then he learned of the ADAPT study. His final session was a few weeks ago.

"It was a godsend," Boykin said. "They brought me out of the hole I was in."

The venlafaxine provided immediate relief. But for him, "the talk therapy was almost as important as the drug therapy," Boykin said. "(Senior clinician) Sunita (Chickering) was extremely effective at uncovering problems - chiefly anger issues - I've had over the years."

His back pain is pretty much gone, Mr. Boykin said. And although he still feels depressed from time to time, "at least I know now how to deflect it."

A Soldier’s War on Pain - NYTimes.com

Four years and a lifetime ago, a new war began for Sgt. Shane Savage.
On Sept. 3, 2010, the armored truck he was commanding near Kandahar, Afghanistan, was blown apart by a roadside bomb. His head hit the ceiling so hard that his helmet cracked. His left foot was pinned against the dashboard, crushing 24 bones.
Sergeant Savage came home eight days later, at age 27, with the signature injuries of the conflicts in Iraq and Afghanistan: severe concussion, post-traumatic stress and chronic pain. Doctors at Fort Hood in Killeen, Tex., did what doctors across the nation do for millions of ordinary Americans: They prescribed powerful narcotic painkillers.
What followed was a familiar arc of abuse and dependence and despair. At one point, Sergeant Savage was so desperate that he went into the bathroom and began swallowing narcotic tablets. He would have died had his wife, Hilary, not burst through the door.
Today Sergeant Savage has survived, even prevailed, through grit, his family and a radical experiment in managing pain without narcotics. When off-duty, he pulls on cowboy boots and plays with his children, does charity work and, as part of a therapy program, rides horses. The only medication he takes for pain is Celebrex, a non-narcotic drug.
"You have to find alternative ways to get out and do stuff to stay active, to get your brain off the thought process of 'I'm in pain,' " said Sergeant Savage, whose ears push out from under a Texas A&M baseball cap.
The story of Sergeant Savage illuminates an effort by experts inside and outside the military to change how chronic, or long-term, pain is treated. By some estimates, tens of millions of Americans suffer from chronic pain, and the use of opioids — drugs like hydrocodone, methadone and oxycodone (the active ingredient in painkillers like OxyContin) — to treat such conditions has soared over the last decade.
This opioid boom was a result of a synchronized drumbeat sounded by pharmaceutical companies, pain experts and others who argued that the drugs could defeat pain with little risk of addiction. Insurers embraced opioids as a seemingly effective and relatively inexpensive solution to a complex problem that often involves psychological and emotional issues.
In recent years, sales of opioids have flattened because of their role in 16,000 overdose deaths annually in the United States, cases that often involve abuse of the drugs. But a growing number of specialists have sharply reduced or stopped their prescription of opioids for another reason: their belief that the drugs have led doctors to focus on the wrong goal in treating chronic pain.
Opioids blunt a patient's discomfort for a time. But the drugs can become a barrier to improving how well a patient functions physically and socially, goals that appear crucial in combating chronic pain, many experts say. As a result, specialists are returning to strategies that were popular before the opioid era, like physical therapy, behavior modification and psychological counseling. Others are exploring alternative treatments like acupunctureand yoga.
Many pain programs now use non-opioid drugs, including ones developed for conditions like epilepsy, that are also effective in relieving pain. "We have to change the paradigm and the culture," said Dr. Karen H. Seal, who specializes in pain treatment at the Veterans Affairs Medical Center in San Francisco and has studied the use of opioids and other drugs in combat veterans.
More ...

http://www.nytimes.com/2014/05/11/business/a-soldiers-war-on-pain.html?

INvisible Project

The INvisible Project highlights the day-to-day experiences of pain survivors through photographs. These photographs capture the struggles and triumphs of these brave pain survivors. As the INvisible Project allows the outside world a glimpse of what it is like to live with pain while persistently pursuing to live a meaningful life, the goal of this project is to create pain awareness, empower survivors and generate change.



http://www.invisibleproject.org/

What injured squid can teach us about irritability and pain - LA Times

A new study involving injured squid and hungry sea bass may help explain why we are so grumpy and irritable when we are in pain.



For many of us, the unpleasantness of being in pain often goes beyond the agony of the injury. If we are in excruciating discomfort, suddenly it seems everything bothers us -- sounds are too loud, lights are too bright, and even a gentle touch can be uncomfortable.



"One of the effects of pain is the peripheral sensory system becomes hyperactive," said Edgar T. Walters, who studies pain and neural plasticity at the University of Texas Medical School at Houston. "People in pain are very easily irritated and we found that this fits in with a primitive pattern designed for an animal to be extra-vigilant."



Walters is the senior author of a new study in the journal Current Biology that looks at how squid react after having the end of one of their arms snipped off -- a relatively minor injury by squid standards.



The researchers put four injured squid in a tank with four squid predators -- in this case, sea bass. Then they compared the injured squids' behavior to four non-injured squid who were put in the same predator-heavy conditions.



The injury was subtle enough that it didn't effect the squid's ability to swim or maneuver in the water. However, the researchers found it did affect the behavior of the squid.



"The injured squid were really touchy," said Robyn Crook, an evolutionary neurobiologist at the UT Medical School at Houston who led the study. "They responded more strongly to visual stimulus than normal squid. So an encounter a normal squid might just want to keep an eye on caused the injured squid to start up their defense mechanisms."





Squid are the perfect animals to do this type of study on because their defense mechanisms are very specific. Their primary defense is to change color, either to a tan or to make light and dark stripes appear on its body. If they continue to feel threatened they stop swimming, then they swim quickly, and then they release ink.



The researchers also noticed that the sea bass were much more likely to hunt the injured squid. Even though the researchers could not discern any difference in the swimming ability of the injured and non-injured squid, the sea bass clearly could.



"Obviously the fish are evolved to detect the most vulnerable prey, which goes to show just how costly a really minor injury can be to an animal," Crook said.



In another experiment, the researchers anesthetized the squid before snipping its arm. These squid were not hypervigilant, but they were still more attractive to the sea bass, and therefore, they were more likely to be eaten than the injured squid who had not been anesthetized and were super sensitive to any perceived threat.



It seemed the hypervigilance of the injured squid served a useful purpose, leading the researchers to conclude that there is an evolutionary benefit to that hypersensitive sensory state we often find ourselves in after an injury.



"It is not an accident we feel really awful after we are injured," said Walters. "Those sensory changes are really important for increasing survival under conditions where an animal is extremely vulnerable."



So the next time you are around a friend or family member in pain who is complaining about the slightest disturbance in their environment, remember this: If they were in the wild, their hypersensitivity to light, sound and touch might keep them from getting eaten.



http://www.latimes.com/science/sciencenow/la-sci-sn-vigilant-squid-and-the-purpose-of-human-pain-20140507-story.html