Tag Archives: pain

Pain impairs our ability to feel pleasure — and now we know why, and how

Researchers are homing in on the brain circuits that handle pain-induced anhedonia, the reduction in motivation associated with experiencing pain. The findings, currently only involving lab rats, might prove pivotal in our efforts to address depression and the rising issue of opioid addiction.

Pain is definitely not a sensation most of us are excited to experience. And although physical hurt is obviously unpleasant, it isn’t the only component of this sensation. Affective pain can be just as debilitating, and much more insidious. New research has identified the brain circuits that mediate this kind of pain, in a bid to counteract its long-term effects — which can contribute to the emergence of depression and make people vulnerable to addictions that take that pain away, such as opioid use disorder (OUD).

Show me where it hurts

Chronic pain is experienced on many levels beyond just the physical, and this research demonstrates the biological basis of affective pain. It is a powerful reminder that psychological phenomena such as affective pain are the result of biological processes,” said National Institute on Drug Abuse (NIDA) Director Nora D. Volkow, M.D, who was not affiliated with this study.

“It is exciting to see the beginnings of a path forward that may pave the way for treatment interventions that address the motivational and emotional effects of pain.”

Pain, the authors explain, has two components: a sensory one (the part you can feel) and an affective, or emotional, component. Anhedonia — an inability to feel pleasure and a loss of motivation to pursue pleasurable activities — is one of the central consequences of affective pain. Considering the strong links between anhedonia, depression, and substance abuse, the NIDA has a keen interest in understanding how our brains produce and handle affective pain.

Previous studies found that rats in pain were more likely to consume higher doses of heroin compared to their peers. In addition to this, they lost a sizable chunk of their motivation to seek out other sources of reward (pleasure), such as sugar tablets.

The current paper built on these findings, and aimed to see exactly how this process takes place in the brain. The team measured the activity of dopamine-responding neurons in a part of the brain’s “reward pathway” known as the ventral tegmental area. This activity was measured while the rats used a lever with their front paw to receive a sugar tablet. In order to see what effect pain would have on the activity of these neurons, rats in the experimental group received an injection that produced local inflammation in their hind paw. Rats in the control group were injected with saline solution.

After 48 hours, the researchers noted that rats in the experimental group pressed the lever less than their peers, indicative of a loss of motivation. They also saw lower activity levels in their dopamine neurons. Further investigations revealed that these neurons were less active because the sensation of pain was activating cells from another region of the brain known as the rostromedial tegmental nucleus (RMTg). Neurons in the RMTg are, among other tasks, responsible for producing the neurotransmitter GABA, which inhibits the functions of dopamine neurons.

Despite this, when the authors artificially restored functionality to the dopamine neurons, the effects of pain on the reward pathway was completely reversed and the rats regained the motivation to push the lever and obtain their sugar tablet even with the sensation of pain.

In another round of lab experimentation, the team were able to reach the same effects by blocking the activity of neurons which produce GABA in response to pain. The rats who were part of this round of testing were similarly motivated to pick a solution of water and sugar over plain water even when experiencing pain. This, the authors explain, shows that the rats were better able to feel pleasure despite also experiencing pain.

All in all, even though the findings are valuable in and of themselves, the team says that this is the first time a link has been established between pain, an increase of activity of GABA neurons, and an inhibitory pathway effect in the reward system which causes decreased activity of dopamine neurons.

“Pain has primarily been studied at peripheral sites and not in the brain, with a goal of reducing or eliminating the sensory component of pain. Meanwhile, the emotional component of pain and associated comorbidities such as depression, anxiety, and lack of ability to feel pleasure that accompany pain has been largely ignored,” said study author Jose Morón-Concepcion, Ph.D., of Washington University in St. Louis.

“It is fulfilling to be able to show pain patients that their mental health and behavioral changes are as real as the physical sensations, and we may be able to treat these changes someday,” added study author Meaghan Creed, Ph.D., of Washington University in St. Louis.

The paper “Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior” has been published in the journal Nature Neuroscience.

What is pain, and why do we even need it?

Arguably the least enjoyable sensation out of them all, pain always demands attention — and a reaction. But why would biology even give us the ability to feel such a debilitating sensation? Why can’t we just block it out by ourselves? Why even have it in the first place?

Image credits Dimitris Vetsikas.

Pain is unpleasant by design. It needs to be because it is our body’s alarm system. It warns us whenever some bit isn’t functioning correctly, of issues such as disease or infection, and of damage and injury. But, and this is a very important but, it doesn’t always do that. People can feel phantom limb pain even after having a limb amputated. Injuries can be sustained without any feelings of pain, either temporarily or permanently. Our brain can completely block it out if needed. And things such as loud or high-pitched noises can cause us pain without producing any injury (although they can cause these too).

It also “pains us to say this” sometimes. We all know that it’s a figure of speech, especially in work emails, but is there any literal truth behind that?

First off, what is pain?

From our direct experience of it, it’s easy to start seeing pain as punishment — scratch your knee through carelessness, then it starts hurting to get revenge. In actuality, however, pain is meant as a behavioral corrector. Research in the field showed that it doesn’t have to be produced by tissue damage, but rather works as a preventative as well as a protective mechanism. It is so unpleasant and hard to ignore because it was designed from the ground up to get your attention, hold it, and make you want to make it stop.

We all intimately know that pain is an unpleasant, physical sensation. But its current definition also includes its emotional component, meaning that pain can also be a feeling or a constellation of feelings associated with actual or potential harm.

Image via Pixabay.

Physical pain is handled by specialized nerve endings called nociceptors running through and across our bodies. These stay alert for any change that could pose a risk for us, including changes in temperature, chemistry, or pressure. The signals they send to our brains once dangerous thresholds are passed are interpreted or perceived by us as pain. For example, getting bitten hurts because the pressure being applied in that area is almost as great, or greater than, what our skin can safely handle. Keeping your palm on a block of ice for too long starts hurting because it prevents our tissues there from keeping their normal temperature.

Feelings of pain can also be neuropathic in nature (related to damage incurred by the nervous system) or nociplastic (produced by changes in our pain thresholds, generally without injury). The former is the kind of pain you perceive as burning, tingling, or stabbing in your fingers. Diabetes patients often develop long-lasting neuropathic pain, most commonly felt as severe burning pain at night, due to nerve damage incurred by the disease.

It is important to note that like pretty much every other one of our senses, pain doesn’t actually exist, it’s simply a product of our brains. The most concrete manifestation of pain would be the electrical impulses sent out by nociceptors when certain conditions are met. The actual unpleasant sensation you feel, however, is just something your brain creates as it deems necessary. It looks at information such as what threats are present (as informed by our senses), our cognitive state, previous experience with certain types of stimuli, social and cultural norms, and so on.

In other words, when a certain part of you is injured or just not having a good time, it doesn’t hurt; your brain makes you think it hurts. That pain is meant to encourage you to keep said area safe and protected so it can heal. You’ll know how to do so because it will hurt more whenever you don’t. It’s a pretty straightforward system like that.

How we feel it

One thing that I feel is important to note here is that the nerves in our bodies are not made equal.

The nerves in your body are meant to (and are thus specialized to) feel certain kinds of pain in certain ways. For example, the nerves running through your internal organs will readily pick up on distension (stretching), ischemia (reduction in blood flow), or inflammation, beaming these back to you as a diffuse pain. This pain is not highly localized because you don’t really need it to be — all that matters is that you understand there’s something going on inside your belly and you should manage it.

What these visceral nerves are not good at, however, is feeling stuff like cuts or burns. The ones in your skin, meanwhile, are very good at picking up on these, and they’re also very good at pinpointing exactly where the pain comes from. It’s much more important to know where you got a cut on your skin so you can keep it clean and prevent infection, so your body supplies this information.

However, at the end of the day, all nerve fibers make their way to the same spinal cord. But because both areas with a higher sensory density (skin, for example) and those with low sensory density (such as viscera) end up here, their data can get scrambled up. This can produce an effect where pain from one low-sensitivity area can be interpreted as coming from a high-sensitivity area.

Types of pain

A pain management chart, meant to help patients more accurately describe the levels of pain they’re feeling. Image credits LPWaterhouse / Flickr.

The first one we’ll talk about today is ‘referred‘ or ‘reflected’ pain, that’s felt in one part of the body but produced by injuries in another. For example, a kidney stone will make your back hurt, and a stroke can make your jaw sore. Referred pain is produced because the nerve pathways serving the injured areas also connect to others, which may mess up where our brains perceive the pain (although we don’t yet have a good grasp on why it happens). There is also ‘radiating‘ pain, similar to the referred one, with the slight difference that the sensation is also felt in the area that has sustained an injury, not just away from it.

Acute pain is diagnosed mostly based on duration and re-emergence. If the pain can be resolved quickly it is considered to be acute. The exact definitions are still a bit blurry, and the time window used to determine acute pain has varied from 30 days to 6 months, even up to 12 months. One simple way to describe acute pain is that it doesn’t extend beyond the expected period of healing, or that it is short-lived.

On the other hand, we have chronic pain. This can last for years, even your whole lifetime, if you’re particularly unlucky. This can be produced by a variety of conditions, although doctors sometimes make a distinction between cancer-related and benign chronic pain. One easier way of describing it is as pain that extends past the expected period of healing, or that it is long-lasting.

Phantom pain sounds spooky, and it is. This is the type of pain individuals sometimes feel in a limb they lost through accident or amputation. Although a part of their body is gone, these individuals still feel (sometimes very significant) levels of pain in that limb. This is a type of neuropathic pain. It’s a very common symptom, occurring in over 80% of upper-limb amputees and over 50% of lower-limb amputees.

Breakthrough pain is often associated with cancer patients, but they’re not the only ones to experience it. Breakthrough pain is a ‘background’ pain that’s usually controlled by medication but sometimes ‘breaks through’ these in bouts of acute pain.

Finally, to your brain, emotional pain is almost the same as the physical kind; which is why breakups are so enjoyable.

How do pain blockers work?

Image credits Arek Socha.

Pain pathways form a very intricate system in our bodies. This is also by design: our ability to feel pain has to be reliable, because it’s meant to keep us alive.

However, our brains can block out pain when needed. If we find ourselves in a dangerous situation where tending to our wounds is not possible — when we’re facing a predator, for example — pain can become counterproductive. The sensation could limit our range of motion or willingness to move and fight in this scenario. As such, our brains temporarily block painful sensations to allow us to escape or prevail. You’ve probably also experienced getting injured during a tense or dangerous situation and only later noticing it. Adrenaline or states of shock can also block out the sensation of pain.

This process takes place without our input and isn’t reproducible at will. Still, having the ability to stop pain is very handy, so we’ve developed ways of doing so. Anesthetics or pain blockers work by either preventing nerve endings from transmitting pain signals to the brain, or in one way or another stopping the brain from producing a painful sensation.

General anesthesia, for example (the kind you’d get before surgery) disrupts nerve activity throughout your whole body. This prevents us from feeling pain while under anesthesia, and blocks our recollection of it afterwards. All the extra bits that come with general anesthesia — the specialized doctor who administers the drugs and monitors you, tubes to feed oxygen into your lungs, monitoring devices — are all there because anesthesia basically shuts down your nervous system. If not done properly, this can and will kill you, most commonly by breaking the communication lines between your brain, heart, and lungs.

There are four stages to general anesthesia — induction, delirium, surgery anesthesia, and overdose.

  • Induction starts when the drugs are administered, and lasts until you fall asleep. During this stage, you’ll still be able to talk and focus to some extent. However, your breathing will slow down, and you’ll slowly lose the ability to feel pain.
  • The delirium phase is quite dangerous, and an anesthesiologist will do their best to make it last for as brief a time as possible. This step takes place as the nerves connecting your body to your brain stop working properly, making bits of you act weird. The delirium phase can produce uncontrolled movements, irregular breathing, and can lead to an increase in your heart rate. It’s also possible to see patients vomit during this stage, which can be quite deadly (there is a significant risk of choking).
  • In the surgical anesthesia phase, things calm down a little. A patient’s eyes stop moving and their muscles relax completely. It’s very possible that a patient in this state is unable to breathe unassisted. This is the ideal state for surgery and the one an anesthesiologist will try to keep you in as it is the least dangerous stage apart from induction.
  • The overdose stage takes place if too much anesthesia is administered to a patient. It’s rarer nowadays, but it’s still a very dangerous event with a high risk of being fatal. The risks are related to the communication lines between your brain, heart, and lungs going completely silent. If a patient is not brought up fast enough, or his breathing and heartbeat not maintained artificially, he will die.

Local anesthesia is far less powerful, affects a much smaller, more controlled area, but it’s also less risky. The most reliable way to differentiate local from general anesthesia is that the former involves loss of pain sensation but not loss of consciousness — general anesthesia leads to a temporary loss of both.

Local anesthetics typically work by blocking certain biochemical pathways inside nerve cells in a certain area. Most commonly, they target sodium ion pumps on the membranes of cells. This effectively prevents those cells from sending signals to the brain, as the electrical signals our bodies rely on are mediated by ions zipping here and there over nerve cells.

Psychological pain

Image via Pixabay.

The muddier and arguably worse type of pain, psychological pain can be summarized as ‘suffering’. It’s also referred to as emotional or mental pain, and is usually described as a deeply unpleasant but hard to delineate feeling.

Since people are complex creatures, psychological pain is hard to define in concrete terms. It encompasses a wide range of feelings and subjective experiences produced by the awareness of negative events or changes in one’s life, abilities, bodily functions, social standing, and so forth. Perceived shortcomings or deficiencies in the self can also lead to psychological pain. Losing a loved one is a major cause of psychological pain and, for better or for worse, an inescapable part of being human.

Being a deeply subjective experience, psychological pain is much harder to discuss in concrete terms. One of the most commonly used definitions of psychological pain today is that it is caused by our unmet psychological needs (making it the opposite of happiness). Unlike physical pain, it is most often described as being a diffuse sensation without necessarily having a known cause, is seen as generally long-lasting, and as having an adverse effect on the self and our ability to function.

Art has long grappled with themes of suffering, emotional distress, how these impact us, and it may be, in many ways, one of our most efficient tools in learning how to deal with psychological pain on a personal level. Therapy also works wonders. You can mix and match them if you need to.

To wrap things up

Pain, to hold to the definition we started this journey with, is meant to help correct our poor behavior — i.e. do things that hurt your body then feel pain, so, hopefully, you’ll stop doing the bad thing. Psychological pain, then, can also be seen as a way to correct our poor behavior in the social or cognitive realm.

This gives pain, and especially suffering, a strange double nature. They both are supremely unpleasant to us, but they are also great teachers. People will go to great lengths to avoid pain, which shows just how great this feeling is at correcting behavior. In fact, Freudian psychology considers the ability to endure pain now for a worthy outcome (delayed gratification) as the hallmark of maturity, as we don’t really have free will until we can face the fear of pain and overcome it (the pleasure principle vs reality principle).

People have recognized this nature for millenia now. The oldest stories we know of, such as the Epic of Gilgamesh, the Iliad, or creation myths around the world, delve deeply into experiences such as loss of a loved one and/or rebirth, loss of social standing and power, of being far away from home unable to return. Characters, be they mortals or gods, are shown to pass through suffering and emerge anew on the other side — sometimes stronger, sometimes weaker for it. Others, like Darth Vader for example, try and fail to overcome their suffering, and become defined by it until they succeed. Those are the kinds of stories that still captivate us because we can all understand and have experienced psychological pain, and desire to see our heroes and villains overcome it and get their due.

I’ll end with a quote from Fyodor Dostoevsky, a titan of the Russian novel, that I feel perfectly encapsulates humanity’s unique relationship to pain. Dostoyevsky started his adult life as an idealistic, passionate political reformist. A religious awakening after a mock execution and a real sentence in a Siberian labor camp (he was a very interesting guy) led him to a captivation with how the human ‘soul’ (in his words) or psychology (in modern parlance) works. His writing is very good, if at times disjointed (he was suffering from a particularly debilitating form of epilepsy), so go read them if you like exploring new depths of despair. But until then I leave you with this quote from his 1864 book Notes from the Underground:

“And why are you so firmly, so triumphantly, convinced that only the normal and the positive — in other words, only what is conducive to welfare — is for the advantage of man? Does not man, perhaps, love something besides well-being? Perhaps he is just as fond of suffering? Perhaps suffering is just as great a benefit to him as well-being?”

“Man is sometimes extraordinarily, passionately, in love with suffering, and that is a fact.”

Helping others helps your brain feel less pain

Doing good for others may do us good in turn, a new paper suggests. Engaging in altruistic behavior without expecting something in return can lessen physical pain, it found.

Image via Pixabay.

Most people like doing good things for others. Altruistic behavior has been shown to trigger the release of neurotransmitters such as dopamine in the brain, which amplify nice cozy feelings. But the same chemicals can lessen our subjective perception of pain, a new paper reports.

Pain Less

“We find consistent behavioral and neural evidence that in physically threatening situations acting altruistically can relieve painful feelings in human performers,” the study explains.

The team carried out four experiments to see if engaging in altruistic behavior could alter the way people perceive pain. In the first experiment, they asked donors who gave blood after an earthquake to rate how painful the needle jab was to them. They also did this with volunteers who gave blood without a disaster having occurred recently (this acted as the control group). Those in the first group reported feeling less pain when jabbed with the needle, the team explains.

In the second experiment, the team asked participants to fill out some questionnaires while exposed to cold temperatures. Additionally, each participant could opt to help revise a handbook for migrant children with their questionnaire. Those that accepted formed the experimental group, while those that opted out of the revision task were placed in the control group. Both groups performed the same task, including the revision, but the control group was told that they were given regular counseling handbook (i.e. that the revision wasn’t altruistic in nature). The researchers report that those who volunteered for this task felt less discomfort associated with the cold than the participants who didn’t volunteer.

For the third experiment, the team asked cancer patients to report on their pain levels. Two groups were established: patients that cared (doing cooking, cleaning, etc.) only for themselves, and those that cared for others as well. The second group reported lower levels of pain overall, the study found.

In the final experiment, the team asked volunteers for donations to help orphans and asked those that did donate how much they thought their donation helped the cause. Each volunteer then underwent an MRI scan while receiving mild electrical shocks. Participants who donated showed a lower brain pain response than those who didn’t, and the more a volunteer thought that their donation helped, the lower this response.

The team explains that their findings suggest altruistic behavior not only makes you feel good but can also reduce our perception of pain.

“This reduced pain-induced activation in the right insula was mediated by the neural activity in the ventral medial prefrontal cortex (VMPFC), while the activation of the VMPFC was positively correlated with the performer’s experienced meaningfulness from his or her altruistic behavior,” the team concludes.

As for why this happens, the authors write that it’s probably one of the “psychological and biological mechanisms underlying human prosocial behavior”, meant to promote cooperation between individuals and cement social networks. However, it’s not all rainbows and roses: previous research has shown that altruism and punishment are two sides of the same coin, and are used liberally to enforce the prosocial behavior in individuals.

The paper “Altruistic behaviors relieve physical pain” has been published in the journal PNAS.

Hippocampus.

Researchers identify clump of neurons that block, or allow, frightful memories into our minds

New research is looking into the cells that block, or allow, frightening memories to pop up into our minds.

Hippocampus.

Image credits Henry Gray / Anatomy of the Human Body (1918) via Wikimedia.

Researchers at The University of Texas at Austin have identified the group of neurons that handle scary, recurrent memories. The findings could help us better tailor therapy for the treatment of anxiety, phobias, and post-traumatic stress disorder (PTSD).

Frightful relapse

“There is frequently a relapse of the original fear, but we knew very little about the mechanisms,” said Michael Drew, associate professor of neuroscience and the senior author of the study. “These kinds of studies can help us understand the potential cause of disorders, like anxiety and PTSD, and they can also help us understand potential treatments.”

Drew and his team worked with a group of lab mice, which they trained to associate a distinctive box with fear. Each mouse was repeatedly placed inside the box and given a harmless electrical shock until they started associating this box with feelings of pain. Needless to say, this rendered the mice quite scared of having to go inside said box.

The end result was that the mice would display fear when inside the box. In the second step of the experiment, the same mice were placed inside the box without receiving the shock. They kept displaying fear initially, the team reports. However, as exposure to the box continued without the shock being administered, the association weakened. Eventually, the mice stopped showing signs of fear. The authors explain that repeated exposure without the painful shock created extinction memories in the mice’s minds in place of the earlier, painful and fear-inducing memories.

This is a glimpse of how our brain stores and handles conditioned responses, a process which has been heavily studied and documented ever since Pavlov and his drooling dogs. However, there are still things we don’t understand. Among these, and something the team wanted to understand, is how and why memories or responses we thought were behind us can still pop up in our minds, triggering spontaneous recovery (think of it as a form of traumatic-memory relapse).

In order to find out, they artificially activated fear responses and suppressed extinction trace memories through the use of optogenetics (a technique that uses light to turn neurons on or off).

“Artificially suppressing these so-called extinction neurons causes fear to relapse, whereas stimulating them prevents fear relapse,” Drew said. “These experiments reveal potential avenues for suppressing maladaptive fear and preventing relapse.”

Drew’s team was surprised to find that the brain cells responsible for suppressing or allowing fear memories to surface are nestled in the hippocampus. The traditional view is that fear is born of the amygdala, the primitive ‘lizard’ level of our brains. The hippocampus is actually heavily involved in aspects of memory, but generally in the process of linking memory with spatial navigation. The team’s hypothesis is that the hippocampus’ job is to provide spatial context for memories, i.e. where something happened or how you got there.

Their findings could, therefore, explain why exposure therapy — one of the most common treatment avenues for fear-based disorders — sometimes simply stops working. Exposure therapy works by creating safe (extinction) memories to override the initial, traumatic one. For example, someone who’s scared of spiders after being bitten by one can undertake exposure therapy by letting a harmless spider crawl on his hand.

While the approach is sound, the team reports, it hinges on our hippocampus‘ willingness to play ball.

“Extinction does not erase the original fear memory but instead creates a new memory that inhibits or competes with the original fear,” Drew said.

“Our paper demonstrates that the hippocampus generates memory traces of both fear and extinction, and competition between these hippocampal traces determines whether fear is expressed or suppressed.”

The findings suggest we should revisit how we time exposure therapy, and how frequently patients should undergo exposure sessions, according to the authors.

Paper DOI http://dx.doi.org/10.1038/s41593-019-0361-z

SAFit2.

New study wants to tackle depression, obesity, chronic pain by blocking a single protein

New research aims to shut down a protein linked to major depression, obesity, and chronic pain.

SAFit2.

The new inhibitor (colored orange) only blocks the activity of FKBP51, which is involved in depression, chronic pain and obesity.
Image credits Felix Hausch.

One protein known as FK506-binding protein 51, or FKBP51 for short, has previously been linked to depression, obesity, diabetes, and chronic pain. A new study is looking into ways we can block its activity in mice, in an effort to relieve chronic pain and have positive effects on diet-induced obesity and mood. The new compound could also have applications in alcoholism and brain cancer, the team explains.

The problematic protein

“The FKBP51 protein plays an important role in depression, obesity, diabetes and chronic pain states,” says Felix Hausch, Ph.D., the project’s principal investigator.

“We developed the first highly potent, highly selective FKBP51 inhibitor, called SAFit2, which is now being tested in mice. Inhibition of FKBP51 could thus be a new therapeutic option to treat all of these conditions.”

Hausch said he became “intrigued” by the protein’s peculiar role in the body, especially its link to depression. So, together with his team, he set about trying to shut it down. Among others, the protein can limit glucose uptake in cells and the browning of fat, which, taken together, can make our bodies store adipose tissue instead of shedding it. It also has a part to play in regulating our stress responses, Hausch adds, so finding a way to block FKBP51 could help treat a variety of conditions.

But here’s the catch: FKBP51 is extremely similar in structure to FKBP52, even though they perform almost opposite roles in cells. It is exceedingly difficult, then, to develop a drug that interacts with only one of these proteins and not the other. To tackle this issue, the team used nuclear magnetic resonance techniques to look at the FKBP51 protein, and discovered a new binding site.

“We have this yin-yang situation,” Hausch says. “Selectivity between these two proteins is thought to be crucial, but this is hard to achieve since the two proteins are so similar. We discovered that FKBP51 can change its shape in a way that FKBP52 can’t, and this allowed the development of highly selective inhibitors.”

Based on their analysis, the team started developing SAFit2, a substance they say could work to inhibit the activity of FKBP51 — and only FKBP51. Animal testing revealed that SAFit2 can help mice “cope better in stressful situations”, Hausch reports. It reduced stress hormone levels, promoted more active stress coping, was synergistic with antidepressants, protected against weight gain, helped normalize glucose levels, and reduced pain in three animal models.

Besides SAFit2, the approach they developed could help other researchers identify similar “cryptic” binding sites in challenging drug targets in the future, Hausch says.

The findings so far are pretty exciting, the team explains, but much more work needs to be done before we have FKBP1 inhibitors that are safe to use in human tests. Until then, they are exploring the potential applications of such compounds in animals. They’re also interested in using such inhibitors to treat alcoholism and have already started digging into this idea, but the results are still too early to report on.

Hausch also says that certain types of glioblastoma tumors overexpress FKBP51. This suggests that FKBP51 inhibitors might be used to treat cancer in patients whose tumors mutate beyond what current medication can treat.

“We may be able to resensitize them to different types of chemotherapy using these specific inhibitors,” he says.

The findings have been presented at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition under the title “Selective FKBP51 inhibitors enabled by transient pocket binding.”

Jo Cameron (left) feels no physical pain and heals quickly. Her abilities are caused by two genetic mutations which may one-day be targetted in novel pain-relief treatments. Credit: Jo Cameron.

Scottish woman who feels no pain and heals without scars might help create novel painkillers

Jo Cameron (left) feels no physical pain and heals quickly. Her abilities are caused by two genetic mutations which may one-day be targetted in novel pain-relief treatments. Credit: Jo Cameron.

Jo Cameron (left) feels no physical pain and heals quickly. Her abilities are caused by two genetic mutations which may one-day be targeted in novel pain-relief treatments. Credit: Jo Cameron.

Jo Cameron, a 71-year-old Scottish woman, has lived all her life without the sensation of physical pain. Although what you might think at first glance, living without feeling pain comes with its own challenges and problems. For instance, the woman has suffered numerous burns and cuts, which often inflicted more damage than they should have. Sometimes, Cameron would realize her skin was burning only after she smelled fumes coming out of her flesh. But luckily Cameron possesses another superman trait: she heals quickly and often with very little or no scarring at all. In a new study, scientists have found that these traits are due to a newly identified genetic mutation — one that could pave the way for new treatments.

‘X-woman’

Cameron’s extraordinary abilities first came to doctors’ attention when, only a few years ago, she sought treatment for a hip injury. Her hip proved to have severe arthritis and required replacing. Immediately doctors knew something was off since Cameron’s disease should have caused her immense discomfort, which wasn’t the case. After two painless surgeries, doctors decided they should investigate more closely this unique patient.

“We had banter before theatre when I guaranteed I wouldn’t need painkillers,” the woman told BBC News, recounting the moment her doctors couldn’t believe she wouldn’t need painkillers after her surgery.

“When he found I hadn’t had any, he checked my medical history and found I had never asked for painkillers.”

Doctors at Raigmore Hospital, Inverness, ran some tests on her finding that the woman had almost no pain response. She could even eat Scotch bonnet chillis, which are famous for being extremely hot, without so much as flinching.

Cameron was then referred to experts in pain genetics at the University College London and the University of Oxford who identified two mutations that may be linked to her pain sensitivity and healing ability. One is a mutation that affects a gene called FAAH (Fatty Acid Amide Hydrolase), which plays a major role in regulating the body’s endocannabinoid system — a family of endogenous ligands, receptors, and enzymes that are important in pain, memory, and mood. The endocannabinoid system is also the target of compounds in cannabis which provoke a ‘high’ or ‘buzz’ once they are ingested.

The second mutation targets a gene which previously had no apparent useful purpose. The new research, however, shows that this mutation switches the FAAH gene on or off. In the case of Cameron, the gene’s activity is switched off, the authors reported in the British Journal of Anaesthesia.

These mutations may explain why Cameron doesn’t feel physical pain or heals so quickly. What’s more, there may also be some psychological effects. For instance, Cameron scored zero on clinical tests for anxiety and depression. She says she never panics or loses her cool — not even when she was in a recent car accident.

But despite her rare condition, Cameron says that she would have preferred to feel pain.

“Pain is there for a reason, it warns you – you hear alarm bells.”

“It would be nice to have warning when something’s wrong – I didn’t know my hip was gone until it was really gone, I physically couldn’t walk with my arthritis.”

Scientists hope to translate the findings into novel drugs that annihilate the pain response. Right now, half of the patients recovering from surgery still experience pain despite taking strong painkillers. In the future, researchers hope to study other people with the same kind of mutations. In 2013, ZME Science wrote about a similar case — that of Ashlyn Blocker, a normal looking American teenager from a small town called Patterson, GA.

 “People with rare insensitivity to pain can be valuable to medical research as we learn how their genetic mutations impact how they experience pain, so we would encourage anyone who does not experience pain to come forward,” Dr. James Cox, of UCL, told the BBC.

“We hope that with time, our findings might contribute to clinical research for post-operative pain and anxiety, and potentially chronic pain, PTSD and wound healing.”

Credit: Pixabay.

Poor sleep makes people more sensitive to pain

Scientists have found that inadequate sleep ramps up activity in pain-sensing regions of the brain. At the same time, brain areas responsible for how we perceive painful stimuli decreased in activity.

Credit: Pixabay.

Credit: Pixabay.

The fact that sleep and pain have an intertwined relationship, feeding off of one another, is well established. Previously, a study published in the journal PAIN performed a pain sensitivity test by having participants submerge their hands in cold water. The findings showed that 42% of participants with insomnia were more likely to take their hands out early compared to only 31% of the insomnia-free participants, and that the pain sensitivity increased with the frequency and severity of insomnia. Another study published in 2006 found that just one night of poor sleep was enough to increase a person’s sensitivity to pain.

Sleep deprivation may make a person more sensitive to pain because it enhances the production of pro-inflammatory proteins called cytokines. These are the molecules that stimulate the movement of inflammatory cells such that, in the event of a foreign invader, the body may respond by calling white blood cells to the site of infection. Usually, inflammation is helpful because it leads to healing. However, when the inflammatory reaction is constantly stimulated, the white blood cells can end up affecting healthy organs, tissues, and cells. If a person is already suffering from arthritis or fibromyalgia, sleep deprivation can aggravate their symptoms and may even disrupt how that person responds to medication.

In two new studies led by Matthew Walker, a Professor of Neuroscience and Psychology at the University of California, Berkeley, and founder of the Center for Human Sleep Science, researchers investigated how the brain processes pain after sleep deprivation. In the first part of the study, participants were recruited from Amazon’s Mechanical Turk and had to report how their pain sensitivity fluctuated after sleeping poorly the night before. In the second part, participants had their brain activity scanned while they were kept awake through the night in the lab.

The results suggest that sleep-deprived individuals who performed a pain sensitivity task showed increased activity in the primary somatosensory cortex (which is responsible for detecting pain) and reduced activity in regions of the striatum and insular cortex (which have many cognitive roles, among them perception).

About 50 to 70 million Americans suffer from some degree of sleep deprivation, from insomnia to obstructive sleep apnea, to chronic sleep deprivation. The results are important in this context — perhaps better sleep could be an effective way to manage pain, especially in a hospital setting.

The findings appeared in the Journal of Neuroscience.

pain treshold

Pain, the self-fulfilling prophecy: When we expect something to hurt, it does

pain treshold

Credit: Pixabay.

Our expectations have far-reaching consequences: they can influence learning and sports performance — and, apparently, how we respond to pain. According to researchers at the University of Colorado, Boulder, expecting a certain pain intensity can become a self-fulfilling prophecy. For instance, expecting a vaccine shot to hurt will probably result in this feeling — even if that needle poke isn’t really painful at all. What’s more, this response persists even when reality demonstrates otherwise.

“We discovered that there is a positive feedback loop between expectation and pain,” said senior author Tor Wager, a professor of psychology and neuroscience at the University of Colorado Boulder. “The more pain you expect, the stronger your brain responds to the pain. The stronger your brain responds to the pain, the more you expect.”

Wager and colleagues wanted to investigate why pain expectations are so entrenched and resistant to change. The researchers were inspired to carry out the new study after noticing that test subjects participating in Wager’s lab for various research often continued to expect something to hurt badly even though they were shown time and time again that the stimulus wasn’t painful at all.

The research team recruited 34 volunteers who were taught to associate one symbol with low heat and another with high, painful heat. Each participant was then seated inside a fMRI machine that records neural activity. For an hour, the subjects were shown various cues representing low or high pain — the symbols that they were trained to associate earlier, but also words like “Low” and “High”, or the letter L and W —  and then rated how much pain they expected to receive.

Next, a painful but non-damaging heat was applied to the volunteers’ forearm or leg, then they were asked to rate the pain. The most painful stimuli was “about what it feels like to hold a hot cup of coffee” according to Wager.

The volunteers weren’t told that there was actually no relationship between the intensity of heat they felt and the preceding cues. Nevertheless, when the subjects expected more pain due to the cues, brain regions associated with threat detection and fear became activated. When they actually received the stimulus, brain regions involved in the generation of pain lit up more. Regardless of how much heat they actually received, the participants generally reported more pain following exposure to high-pain cues.

“This suggests that expectations had a rather deep effect, influencing how the brain processes pain,” said Marieke Jepma, then a postdoctoral researcher in Wager’s lab.

And it seems like the brain has even more tricks to play on us. When the participants expected high pain and got it, the next time they would expect even more pain. However, if they expected high pain and didn’t get it, nothing changed — an example of confirmation bias in action. Confirmation bias can prevent us from considering other information when making decisions since we tend to only see factors that support our beliefs.

“You would assume that if you expected high pain and got very little you would know better the next time. But interestingly, they failed to learn,” said Wager.

The findings could prove important for medicine in settings where pain management is important. For instance, the study may explain why in some instances patients whose damaged tissues have healed still have chronic pain.  

“Our results suggest that negative expectations about pain or treatment outcomes may in some situations interfere with optimal recovery, both by enhancing perceived pain and by preventing people from noticing that they are getting better,” Jepma said. “Positive expectations, on the other hand, could have the opposite effects.”

The findings appeared in the journal Nature Human Behaviour.

Why do people self-harm? New study offers surprising answers

If you’ve seen HBO’s newest miniseries, Sharp Objects, you’re well familiar with what doctors call NSSI: non-suicidal self-injury. NSSI is a serious mental health condition, but despite years of research, we’re still not quite sure why individuals engage in this type of behavior. A new study performed at St. Edward’s University in Austin, Texas, sought the answer to this question by drawing on existing theories in the literature.


Previous studies have shown that individuals who exhibit NSSI have low levels of β-endorphin, which is produced to mediate stress-induced analgesia (the inability to feel pain) — and high ratings of clinical dissociation, which is a feeling of disconnection with oneself and one’s surroundings. The researchers hypothesized that NSSI individuals are attempting to restore these imbalances using self-harm. To test their hypothesis, researchers recruited participants from the university. Using saliva samples and surveys, they assessed β-endorphin levels and psychological state before and after a procedure called the cold-pressor test.

[panel style=”panel-info” title=”Cold-Pressor Test” footer=””]During the cold-pressor test, an individual immerses his or her hand in a bucket of ice water. Researchers then note how long it takes the individual to feel pain (their pain threshold) and how long until the pain is unbearable (pain tolerance), at which point the test ends.
[/panel]

They discovered that non-suicidal self-injurers have lower levels of arousal than people without these tendencies (the control group). After the pain challenge, their arousal levels matched the baseline of the control group — in other words, experiencing pain was able to correct their low levels of arousal. The pain challenge also decreased symptoms of dissociation. However, these changes weren’t exclusive to the NSSI group: the control group also experienced an increase in arousal and a decrease in dissociative symptoms after the cold-pressor test.

Next, the researchers sorted the NSSI group by symptom severity. They found that the more severe the individual’s NSSI symptoms, the stronger their dissociative symptoms were. However, only the most severe cases experienced a reduction in these symptoms after the pain challenge. Another interesting finding is that the NSSI individuals with moderate symptom severity actually had higher levels of β-endorphins (both before and after the pain challenge). This wasn’t seen in those with low or high symptom severity.

However, perhaps the most surprising part of the study was the high percentage of NSSI participants. 

“The literature states that there’s a 5% prevalence of NSSI in the general population, and we found this in 17 out of 65 participants, which is way above what we would expect, even when taking into consideration that university students tend to have a higher NSSI rate than the general population,” said Haley Rhodes, who presented the research at the 2018 Society for Neuroscience Meeting.

Rhodes admits that a bigger sample size is necessary before we can draw full conclusions from the data, but it’s intriguing that there seems to be a minor psychological benefit to the pain — though it most definitely doesn’t warrant any self-harming practices.

Understanding the imbalances in individuals that partake in NSSI might help us find a way to provide for their psychological needs, and allow them to get the same benefits without needing to resort to self-injury.

 

 

Researchers at Max Planck developed a new fitness technology called Jymmin makes us less sensitive to pain. Credit: Max Planck Institute For Human Cognitive and Brain Sciences.

Jymmin combines working out with music, makes people feel less pain

Good news for all of us! Whether or not you’re enjoying exercising, scientists have developed new technology that makes working out more enjoyable than ever. The new study also found that it makes us more resistant to pain.

Researchers at Max Planck developed a new fitness technology called Jymmin makes us less sensitive to pain. Credit: Max Planck Institute For Human Cognitive and Brain Sciences.

Researchers at Max Planck developed a new fitness technology called Jymmin that makes us less sensitive to pain. Credit: Max Planck Institute For Human Cognitive and Brain Sciences.

Researchers at Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) developed a new way of working out: they altered fitness machines to produce musical sounds during use. Scientists discovered that this novel approach, which they call Jymmin, increases pain threshold and makes people less sensitive to discomfort.

“We found that Jymmin increases the pain threshold. On average, participants were able to tolerate ten percent more pain from just ten minutes of exercise on our Jymmin machines, some of them even up to fifty percent”, said Thomas Fritz, head of research group Music Evoked Brain Plasticity at MPI CBS, in a press statement.

How do these machines work?

Scientists paired music composition software with sensors attached to the fitness machines. While exercising, the sensors captured and then transmitted signals to the software, which played back an accompaniment from each fitness machine. Basically, the researchers modified steppers and abdominal trainers to become our own musical instruments, so you can get really creative while working out.

Researchers discovered that, after Jymmin, participants were able to immerse their arms in ice water of 1°C (33.8°F) for five seconds longer compared to a conventional exercise session.

Scientists believe that the pain resistance experienced by the participants is due to the increased release of endorphins. Apparently, if music composition and physical activity are combined, endorphins are flushed into our systems in a more efficient way.

Researchers divided all 22 participants according to how they rated pain and discovered that participants with the highest pain threshold benefitted the most from this training method. Maybe this happens because these participants already release endorphins more effectively in comparison to those who are more pain sensitive.

“There are several possible applications for Jymmin that can be derived from these findings. Patients simply reach their pain threshold later,” Fritz added.

Jymmin could do wonders in treating chronic or acute pain. It could also be used as support in rehabilitation clinics by enabling more efficient training.

Scientists tested top swimmers in South Korea and the results were remarkable: athletes who warmed up using Jymmin machines were faster than those using conventional methods. In a pilot test, five of six athletes swam faster than in previous runs.

Previous studies showed that Jymmin has many positive effects on our well-being. They revealed that personal mood and motivation improved, and even the music produced while Jymmin was perceived as pleasant.

Scientific reference: Thomas H. Fritz, Daniel L. Bowling, Oliver Contier, Joshua Grant, Lydia Schneider, Annette Lederer, Felicia Höer, Eric Busch, Arno Villringer. Musical Agency during Physical Exercise Decreases PainFrontiers in Psychology, 2018; 8 DOI: 10.3389/fpsyg.2017.02312.

Family from Italy can’t feel physical pain because of genetic mutation

A genetic mutation diminished an Italian family’s response to physical pain almost to the point of total insensitivity.

The family members — a grandma, her two daughters and three grandchildren — are all suffering from congenital hypoalgesia, a disease that makes the patient insensitive to pain-inducing stimuli. People with this condition are more prone to a number of injuries, from biting off their lips and fingertips to bone fractures.

Similar cases intrigued doctors worldwide, but, up to now, congenital hypoalgesia has proven mysterious. The study published in the journal Brain casts light upon the condition.

Source: ColiN00B/Pixabay

The researchers from the Wolfson Institute for Biomedical Research, University College London, UK, used a barrage of tests to assess pain resistance in the Marsili family.

The scientists measured the responses of the participants on a scale of 1 to 100. Some of the tests included immersing the participants’ hands in cold water, applying weights and sharp filaments to their forearms and intradermically injecting capsaicin –an active component from chilli peppers that produces a burning sensation.

Next, the scientists sequenced the family’s genome and compared it to that of pain-sensitive humans. They discovered that the ZFHB2 gene had suffered a point mutation. The following phase of the study was to create a mouse model in which the ZFHB2 gene was deleted entirely.

Via Tiburi/Pixabay

The genetically engineered mice lacked reactions to pain, similarly to humans. Scientists found that these mice perceived less pain to thermal and mechanical stimuli than the wild mice group, just like in the human experiment.

Thanks to the rarity of their condition, the Italians made history — the researchers named the disease the Marsili Syndrome. When asked if they would like to feel pain normally, the family told researcher John Wood that they wouldn’t change a thing, reported New Scientist.

The team’s discovery is excellent news for chronic pain patients and for the pharmaceutical companies that are trying to upgrade pain management. Now, new targeted analgesic drugs based on these findings might be manufactured that, hopefully, will aid chronic pain sufferers.

Migraine man.

The crippling pain of migraines makes you more likely to develop a generalized anxiety disorder

Adults who report having more frequent migraines also seem to be much more predisposed to generalized anxiety disorders relative to their peers (6% compared to 2%), a new study from the University of Toronto reports.

Migraine man.

Image credits Gerd Altmann

The study was performed using data from the 2012 Canadian Community Health Survey-Mental Health (CCHS-MS) and drew on a huge sample of people with and without migraines (2232 and 19,270 people respectively). After adjusting for several factors that may play a part in the emergence of generalized anxiety disorder (GAD), the team found that rate of this disorder was “two and a half times higher among those with migraines than those without,” suggesting a powerful link between the two.

So what’s tying the two together? Well, it seems to come down to the “unpredictable and uncontrollable nature” of migraines, the team reports. These seemingly random bursts of pain can cause a lot of anxiety because they often interfere with “family and work impressionability with little or no warning.” First author Professor Esme Fuller-Thomson, Sandra Rotman Endowed Chair at University of Toronto’s Factor-Inwentash Faculty of Social Work and Director of the Institute for Life Course & Aging explains that “this link […] in the past year was partially explained by the disturbingly high prevalence of debilitating chronic pain (30%) and problems in managing household responsibilities (28%) among those with migraine.”

However, this effect can be mitigated to some extent, and the trick is to admit that you may be in over your (aching) head due to the pain. Respondents who didn’t have a person to confide in were roughly five times as likely as those who did to develop a GAD.

Rather surprisingly, the study also found that men who suffer from migraines had almost double the odds of developing a GAD compared to women who reported migraines, the paper adds. Men as a whole are less likely than women to develop GADs in the general population, so this figure was quite puzzling at first.

“This was a surprising finding […],” said co-author Senyo Agbeyaka, a recently graduated MSW student.

“Our results may be due to the fact that men are less likely than women to take medication to treat their migraine and therefore the disorder may be more painful and less controllable, which could result in anxiety.”

The findings show how important it is for doctors to monitor the mental health state — keeping an extra eye out for anxiety disorders — of patients who often suffer from migraines. Men, in particular, are at high risk of developing such conditions, as are those who experience chronic or debilitating pain, people who are struggling to cope with their daily responsibilities and those who are socially isolated.

If you experience a lot of migraines and need some help coping with them, marijuana might help. But there is some evidence that use of cannabis might promote development of anxiety disorders, not to mention that it’s still illegal in many places. Everything considered, a person to confide in and taking some time to rest through a migraine might be the best way to deal with them.

The paper “Characteristics of Headache After an Intracranial Endovascular Procedure: A Prospective Observational Study” has been published in the journal Headache.

Study finds how to predict which brains respond to placebo treatments

A new study offers insight into why a simple sugar pill can work to significantly reduce pain for some patients while having no effect on others.

Image credits Patrik Nygren / Flickr.

A team from the Northwestern Medicine and the Rehabilitation Institute of Chicago (RIC) used fMRI to identify the brain area responsible for the placebo effect in pain relief. This region, known as the mid-frontal gyrus (MFG), is located at the front of the brain and also plays a key role in our decision making and emotional state. The data was recorded in two clinical trials involving 95 patients with chronic pain from osteoarthritis. The team found that participants who had better connectivity between the MFG and other brain areas were more likely to respond to the placebo effect.

The findings could be used to better tailor pain medication to each patient’s brain structure, offering a safer and more efficient alternative to the current trial-and-error approach. In Germany, half of all doctors prescribe placebos for non-chronic illnesses — they might be on to something.

“Given the enormous societal toll of chronic pain, being able to predict placebo responders in a chronic pain population could both help the design of personalized medicine and enhance the success of clinical trials,” said Marwan Baliki, PhD, a research scientist at RIC and assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.

Also, these differences in brain structure could be the reason why some drugs — such as pregabalin, commercially known as Lyrica — provide pain relief in some patients, but not others. By understanding how each patient responds to pain medication, those predisposed to the placebo effect can be eliminated from clinical trials, making future research far more reliable.

“This can help us better conduct clinical studies by screening out patients that respond to placebo and we can just include patients that do not respond. And we can measure the efficacy of a certain drug in a much more effective manner,” he added.

“If we do the same with Lyrica, maybe we can find another area of the brain that can predict the response to that drug.”

Professor of physiology at Feinberg and study co-author Vania Apkarian said that the findings will allow physicians to see what brain regions become active while a patient feels pain, then decide on a drug that specifically targets that area.

“It also will provide more evidence-based measurements. Physicians will be able to measure how the patient’s pain region is affected by the drug,” she added.

The full paper “Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials” has been published in the journal PLOS Biology.

Alzheimer’s disease connected to reduced pain perception

Alzheimer’s disease is a progressive form of dementia that causes problems in memory, thinking and behavior. After sufficient progression, those suffering from it can face extremely difficulty when trying to conduct even simple tasks. Now, a new study from researchers from Vanderbilt University in Nashville suggests that the disease might also hinder people’s ability to recognize when they are in pain.

Image credit Pixabay

Image credit Pixabay

The study spanned three years and examined two groups of adults aged 65 and older. One group consisted of patients with Alzheimer’s disease, while the other was a control group without dementia. Using a device to expose participants to various heat sensations, the researchers gathered self-reported pain levels from each individual and analyzed the results.

“We found that participants with Alzheimer’s disease required higher temperatures to report sensing warmth, mild pain and moderate pain than the other participants,” said Todd Monroe, an assistant professor at Vanderbilt’s School of Nursing and lead author of the study.

Interestingly, although the study found lessened pain recognition in those with Alzheimer’s disease, their pain tolerance remained the same as the control group.

“What we didn’t find was a difference between the two groups in reporting how unpleasant the sensations were at any level,” Monroe said. “While we found that their ability to detect pain was reduced, we found no evidence that people with Alzheimer’s disease are less distressed by pain nor that pain becomes less unpleasant as their disease worsens.”

The inability to detect pain can have a cascade of effects by allowing underlying health issues to go undetected and untreated, ultimately leading to serious problems in the body such as organ damage.

Since the researchers used participant reports to gauge pain levels, the neural mechanisms behind the changes in pain perception found in the study are still unclear. Further research is needed to better understand exactly how Alzheimer’s disease is connected to pain perception and how to help patients detect discomfort, especially when they begin to have difficulties with verbal communication

“As people age, the risk of developing pain increases, and as the population of older adults continues to grow, so will the number of people diagnosed with Alzheimer’s disease,” Monroe said. “We need to find ways to improve pain care in people with all forms of dementia and help alleviate unnecessary suffering in this highly vulnerable population.”

Journal Reference: Contact heat sensitivity and reports of unpleasantness in communicative people with mild to moderate cognitive impairment in Alzheimer’s disease: a cross-sectional study. 10 May 2016. 10.1186/s12916-016-0619-1

In the long run, morphine might actually cause more pain than it alleviates

Painkillers in the opium family (most notably morphine) may actually make pain last longer, a new study reports. Morphine treatment after a nerve injury doubled the duration of pain in rats and this is highly worrying.

Morphine treatment extended the duration of nerve pain in rats, a result that raises questions about the effects of other opioid-based painkillers, such as OxyContin.

It gets even more disturbing when you consider the addictive potential of many commercial opioids such as OxyContin and Vicodin. If this is true, then people are becoming addicted to something that’s extending their pain even longer, suggesting that “the treatment is actually contributing to the problem,” says study coauthor Peter Grace, a neuroscientist at the University of Colorado Boulder.

It’s not the first time opioids have been discussed in this context. Doctors have known for a while that for some people, opioids enhance the pain sensitivity, a condition called opioid-induced hyperalgesia. In this new study, the negative effects lingered for a few weeks even after the treatment was stopped. These experiments were done with male rats, but unpublished data indicate that morphine extends pain even longer in female rats, Grace says. Previous studies suggest there wouldn’t be any major difference between male and female results.

However, this is still just a rat study, and we don’t know if the same effects would be exhibited in humans, nor is it known if all opioids behave similarly. Clarity on how opioids influence pain could change doctors’ prescribing habits and promote better treatments, but the study has to be replicated in humans before we can draw any definite conclusions.

Journal reference: P. M. Grace et al. Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation.Proceedings of the National Academy of Sciences. Published online the week of May 30, 2016. doi: 10.1073/pnas.1602070113.

chronic pain

At least a third of Brits live with chronic pain

After pooling massive amount of data about the health of the UK’s population, researchers found a gradual increase over time in the prevalence of chronic pain. Scientists estimate that 43% of Brits now experience chronic pain or around 28 million people, based on stats gathered in 2013.

chronic pain

Image: Pixabay

There’s no consensus on how many individuals in the UK go about their lives living in chronic pain, despite the extensive literature. Chronic pain is defined as any pain that lasts more than three months due to medical conditions like fibromyalgia, which causes rheumatic conditions, and others.

To get to the bottom of things, researchers at the Imperial College London identified 1737 relevant studies published after 1990. Of these, they selected 19 studies involving 140,000 adults which were deemed relevant enough for a systematic review of chronic pain in the United Kingdom.

The report’s summary:

  • the prevalence of chronic pain ranged from 35% to 51% of the UK’s adult population;
  • moderate to severely disabling chronic pain ranged from 10% to 14% or 8 million people;
  • 43% of the population experience chronic pain, and 14% of UK adults live with chronic widespread pain;
  • 8% of UK adults experience chronic neuropathic pain, and 5.5% live with fibromyalgia;
  • regarding age groups: 18-25 year olds (14% chronic pain prevalence),  18-39 year olds (30% chronic pain prevalence), aged 75 or older (62% chronic pain prevalence).

“Chronic pain affects between one-third and one-half of the population of the UK, corresponding to just under 28 million adults, based on data from the best available published studies. This figure is likely to increase further in line with an ageing population,” the study published in the journal BMJ concludes.

The great prevalence of chronic pain among Britons can be attributed to an aging populace. In a way, that’s excellent news. It’s estimated that one in three children born in the UK in 2012 will live to be 100, but this also comes at an immense burden.

Women in the UK are having fewer children, while the longevity of the population is growing steadily every year. This presents numerous challenges to the job market, pressures the healthcare system, among other things. It also means more and more people have to live in pain.

The UK, one of the leading developed countries in the world, now has to set an example. Its healthcare system needs to shift from primarily extending livelihoods, to improving the quality of life. This is a challenge that the entire planet will have to face at some point.

 

 

bullet ant

Worst pain known to man is caused by world’s largest ant

Quick: Imagine the worst pain you’ve felt. Now, triple it.

That may sound really harsh, but believe it or not, chances are it would still not come close to being stung by the bullet ant, the largest ant in the world. Native to the western rainforests of South America, this insect packs a nasty venomous bite that’s believed to be thirty times more painful than a bee’s sting.

Arguably, it’s the worst pain known to man

bullet ant

Credit: Fewell Lab at Arizona State University

“With a bullet ant sting, the pain is throughout your whole body,” adventurer and naturalist Steve Backshall described on a recent episode of the BBC’s Infinite Monkey Cage. “You start shaking. You start sweating […] It goes through your whole body.”

“Your heart rate goes up, and if you have quite a few of them, you will be passing in and out of consciousness. There will be nothing in your world apart from pain for at least three or four hours.”

Like bees, however, Parponera clavata will only release its potent venom in defense, when threatened. Unlike other ants, there are usually only a few hundred of them in each colony or nest. Nests are usually located at the bases of trees. The worker ants forage all the time in the trees, even getting up to the canopy, but seldom forage on the forest floor. The queen Bullet Ant is a lot bigger than the workers (who are usually about 20 to 30 mm in length). The workers are unyielding, look a bit like a wingless wasp, are reddish-black in color, and are very predacious.

bullet-ant-glove

It’s waiting! Image: The Drip Tray

Some people are hardcore masochists, though, and actively seek the pain. In the case of tribesmen of the Satere-Mawe in Brazil, the reward for wrestling with the bullet ant is manhood. To become initiated as a warrior, teenage boys must wear gloves filled with numerous bullet ants woven in, stinger facing inside, for a full five minutes. During this whole rite, it’s imperative you maintain a calm composure. Initiates must repeat the process at least 20 times to ascend to manhood.

It comes at a price, though. Each session leaves the hand swollen, bruised, and paralyzed temporarily. The boy in question might experience uncontrollable shakiness for days after the rite. That’s why the 20 trials are spread out over several months. One documentary filmmaker, Hamish Blake, tried on the ant gloves for an Australian TV documentary. He could only bear wearing the gloves for a few seconds, which earned him eight hours of excruciating pain.

For what it’s worth, though, the bullet ant’s venom doesn’t last that long. The bruises heal quickly, and the paralysis fades away. In a mere 24 hours, the active ingredient, a neurotoxin called poneratoxin, is completely flushed out of the body. According to toxicological estimates, it would take 2,250 stings to kill a 165-pound human.

“It’s an almost completely pure neurotoxin,” Backshall said. “One of the reasons why people can use it for tribal initiation ceremonies is because although it causes extraordinary pain, it’s not dangerous. There’s almost no allergens. There’s no danger of a histamine reaction to the venom.”

[MORE] Scientist finds the worst places to get stung by a bee – by experimenting on himself. In order, it’s the nostril, lip, and penis

It’s easy to understand why the Satere-Mawe revere their practice so much. Following the rite, the body is completely filled with adrenaline — a rush that can last for weeks.

Adrenaline is a key component of our body’s fight-or-flight response and is used to squeeze every last drop of performance out of our bodies in order to keep us alive. It’s most obvious effects include increased blood flow to muscles, output of the heart, and increased pupil dilation. Adrenaline also primes our internal organs for emergency — it increases blood sugar level, alters which compounds our bodies prioritize during digestion, and how we perceive emotion (it shifts everything closer to fear and/or aggression). On the bright side, it makes us more alert, pushes our muscles into overdrive, and makes us more focused.

Because the bullet ant’s bite is so immensely painful, and because of the sheer number of bites a Satere-Mawe would be exposed to during their initiation right, their nervous systems register it as a particularly dangerous threat — and release a deluge of adrenaline to help them fight it off or run away from it.

“You have such a massive overdose of adrenaline that you feel like a god. For a week afterwards I felt like if I leapt off a cliff I could have flown,” Backshall said.

Ironically, poneratoxin is being explored as a possible pain reliever. In subtle doses, some have found it acts to block pain.

Would you be willing to take an electric shock in the name of curiosity? Science says yes, several actually

Curiosity is probably the single most powerful force behind our species’ scientific discoveries. It can drive us to explore and discover even if the outcome might be painful or harmful. But this need to discover and learn can also become a curse; a new study found that people are willing to face unpleasant outcomes with no apparent benefits just to sate their curiosity.

Curiosity; killer of cats and purveyor of great shots since the dawn of time.
Image credits flickr user Esin Üstün.

Previous research into curiosity found that it can drive humans to seek out miserable or risky experiences, such as viewing gruesome scenes or exploring dangerous terrain, in their search for information. Bowen Ruan and co-author Christopher Hsee from the University of Chicago Booth School of Business believe that our primal need to resolve uncertainty, regardless of personal harm or injury we might endure in the process, is the cornerstone upon which our curiosity is based.

So they designed a series of experiments exposing participants to several unpleasant outcomes, to see how far they would go to obtain a sense of certainty about their environment. In one of the studies, 54 college students were taken to a lab with electric shock pens supposedly left over from a previous experiment. They were told that they were free to pass the time by testing the pens while the experiment they were about to take part in was set up.

*click*
Image credits smartphotostock

Some of the participants had color coded pens — red stickers for the five pens that would deliver a shock, and green stickers for the five that wouldn’t. Others however only had pens with yellow stickers, meaning they didn’t have any certainty what would happen if they clicked them. They were also told that only some of these pens still had working batteries, compounding their level of uncertainty. In the meantime, the team counted how many times each participant clicked each type of pen.

While they waited, students who knew the outcome clicked one green pen and two red ones on average. But those that had no clue what was going to happen clicked noticeably more, around five pens each.

For the second study, another group of students were shown 10 pens of each color. Here too students clicked the pens with uncertain outcomes more than those which were clearly identified as safe or shock-inducing.

“Just as curiosity drove Pandora to open the box despite being warned of its pernicious contents, curiosity can lure humans–like you and me–to seek information with predictably ominous consequences,” explains study author Bowen Ruan of the Wisconsin School of Business at the University of Wisconsin-Madison.

For the third study, the researchers wanted to know how well their findings hold under different circumstances, and if satiating their curiosity would make participants feel worse. They designed a test involving exposure to both pleasant and unpleasant sound recordings. Participants had to choose between 48 buttons on a computer screen, each with a different sound recording attached to it. For example, the “nails” button would play a recording of nails on a chalkboard, buttons labeled “water” played a sound of running water, and buttons labeled “?” could play either sound.

On average, students who had to choose from mostly identified buttons clicked around 28 of them. In contrast, those who had mostly unidentified buttons clicked around 39 of them. Participants who clicked more also reported feeling worse at the end of the experiment. Those who had mostly uncertain buttons reported being less happy overall than those who faced mostly certain outcomes.

The team carried out a separate, online study in which participants were shown partially obscured pictures of unpleasant insects — centipedes, cockroaches, and silverfish for example — and were informed they could click the image to reveal the insect. As with the previous studies, participants clicked on more pictures, and felt worse overall, when faced with uncertain results.

But interestingly, when they were prompted to predict how they would feel about their choice first, their number of clicks went down (and they reported feeling happier overall). This suggests that predicting the consequences of your choice might dampen your curiosity.

So while curiosity is often seen as one of the more desirable human qualities, it can also be a curse. Many times our drive to seek information and satisfy our curiosity can become a huge risk.

“Curious people do not always perform consequentialist cost-benefit analyses and may be tempted to seek the missing information even when the outcome is expectedly harmful,” Ruan and Hsee write in their paper.

“We hope this research draws attention to the risk of information seeking in our epoch, the epoch of information,” Ruan concludes.

The full paper, titled “The Pandora Effect, The power and Peril of Curiosity” has been published online in the journal Psychological Science and can be read here.

Why getting a tattoo hurts — the science behind inking

Your leather jacket and motorcycle aren’t enough for you anymore; they fall woefully short of conveying just how much of a badass you really are. This will not do — everyone must see you in all your glory, the world must know. With a spring in your step, you walk into the best tattoo parlor in town, pick out a design that has a dragon with a skull over explosions and roses and chainswords and… OW! Why do tattoos hurt so much!?

mZQDrA

Well, it’s because tattoos have to get that ink deep enough that it won’t get washed away but not too deep so it remains visible — the ideal location ends up being right next to your skin’s pain receptors. Given that most modern tattoo artists do this with mechanical tools that push a needle into the skin from 80 to 150 times a second, it’s easy to see how tattooing gets its painful reputation. However, people have endured excruciating pain throughout history to adorn their bodies with ink. So why do we do it? How do we do it? And can we make it hurt less? The short answer to the last question is yes. Here’s the longer answer:

Not just ink

Tattooing is a controversial subject — some are all for it, others consider it an art form to be perfected and some think it’s repulsive. To each his own, but the fact remains that throughout history, tattoos have had (and in some cases still have) deep running cultural and social implications. People around the globe have long marked their bodies to express cultural identity and community status; it is one method to connect to one’s ancestors or gods, to mark rites of passage, or even “wear” a permanent amulet.

The term “tattoo” is believed to originate from the Polynesian “tatau”, meaning “to mark,” and Dictionary.com defines it as being “the act or practice of marking the skin with indelible patterns, pictures, legends, etc., by making punctures in it and inserting pigments.” It’s a simple enough process, but the tattoo’s shapes, colors, and position on the body, taken together often hold an incredibly deep meaning throughout time.

In New Guinea, the swirly tattoos on a Tofi woman’s face detail her family lineage, while in Cambodia monks display religious beliefs etched in ink on their chests. The Japanese Yakuza’s spectacular patterns or the US gang member’s sprawling tattoos can show affiliation, rank, or if the wearer has committed murder. The “Iceman” discovered in the Alps in 1991 was covered in tattoos, 85% of which line up with acupuncture points, says Dr. Lars Kurtak, world-renowned tattoo expert and anthropologist with the Repatriation Office of the National Museum of Natural History.

“He appeared to have terrible arthritis. [The tattoos were] so dark, they seemed to be repeated applications and some of them he could not reach on his own,” he notes.

In some cultures, successfully enduring the excruciating pain and the blood loss of tattooing with primitive tools marks the transition from infancy to manhood and is considered deeply sacred rites, notes Joseph Campbell in his book Primitive Mythology: The Masks of God. So in the end, there are as many meanings to tattoos as there have been human cultures throughout history.

How are they made — and why do they hurt?

Early tattooing involved cutting the skin and rubbing ink in the wound or using needles made of bone or wood to push ink into the tissue; Western civilization’s first recorded encounter with the Polynesian practice of tattooing dates from 1769, when naturalist Joseph Banks traveling the world aboard the British Endeavour witnessed the “extensive adorning” of a 12-year-old girl.

“It was done with a large instrument about 2 inches long containing about 30 teeth,” Banks wrote in his journal. “Every stroke […] drew blood.”

Banks also recounts how the girl wailed and writhed but two women held her down, occasionally beating her, for more than an hour until the tattoo was complete.

Thankfully, tattooing changed since then. Modern tattoo artists use clean, precise units to deposit dye by mechanically driving one or several needles soldered together in and out of the skin, usually from 80 to 150 times a second, like this:

https://www.youtube.com/watch?v=FEgeQSyaDqk&feature=youtu.be&t=29s

With each prick of the needle, dye gets injected into the skin, and the body’s immune system responds by deploying white cells called macrophages to deal with the threat. Some of the ink gets lost this way, but most don’t — dead macrophages and the ink they didn’t consume is fixed in skin cells named fibroblasts and remains visible through the thin layers of tissue that cover them.

But we know we can get a scratch and not feel any pain or cut our fingers on paper without so much as a blink. So why is tattooing so notoriously painful? Well, it’s all because of where the pigment needs to go to make a tattoo permanent. Let’s look at your skin’s structure to find out why.

Show me some skin!

The skin is the largest and one of the most complex organs in (on?) the body, serving as the soft outer layer of vertebrates; it’s there to protect and delimitate the juicy, fragile “inside” of the organism from the harsh outside.

There are two distinct parts that make up mammalian skin: the epidermis (this is the outer layer of dead keratinocytes that “flakes” off of to be renewed pretty often) together with the more stable dermis (the layer under it that houses all kinds of glands, hair follicles, blood vessels, lymph vessels and sensory cells) forms the cutis. Directly under the cutis lies the subcutis or subcutaneous tissue, where fatty cells are clumped together to protect you from the cold.

The layer where ink needs to be deposited, the dermis, unfortunately also contains receptor cells that send pain signals to the brain to let us know our body is being hurt; it’s not that bad when you prick your toe on a particularly sharp rock, but when your body is being hurt 80 to 150 times a second, they send out a panicked flurry of signals to the brain, making the experience of getting a tattoo rather unpleasant.

On the bright side, since the dermis doesn’t flake off to be renewed like the epidermis, the dye remains embedded in your skin for life.

The inks or dyes themselves have also evolved over time; as a rule of thumb, tattoo ink is made up of two parts: a pigment and a carrier. The pigment is the substance that gives the ink its color, while the carrier is a solvent that ensures the pigment is evenly mixed, protects against pathogens and aids application. Throughout time, water or alcohol have been the most widely used carriers, while glycerine and denatured alcohols have started being used in modern tattooing.

Pigments have been made from, well, mostly anything colorful; traditional colors were made with materials like simple dirt, pen ink (yay, prisons), soot, even blood. Modern pigments are derived from heavy metals, metal oxides, liquid hydrocarbons, or carbon. But be warned: red dyes, in particular, are known to cause allergies and swelling for a few months after getting a tattoo.

One of the most spectacular (read: insane) pigment recipes I’ve come across hails from ancient Rome and calls for Egyptian pine bark, corroded bronze ground in vinegar, and iron sulfate to be mixed with insect eggs, then soaked in water and leek juice. The concoction would be rubbed energetically on fresh wounds made with needles or blades to create the tattoo. It bugged me.

It really bugged me.

Some tattoos hurt and some tattoos really hurt. Here are some tips

Now, getting a tattoo is going to hurt, there’s no way around that. But there are some areas that are more sensitive to pain than others; as an empirical rule, if you’re extremely ticklish in an area, getting tattooed there is probably going to hurt pretty bad. While keeping in mind that everyone has a different threshold for pain, Tattoos-Hurt.com has put together a chart showing how sensitive different areas of the skin are to pain:

I like how they grade things.
Image via tattoos-hurt

Secondly, a lot of people think that getting a tattoo while hammered or after taking painkillers will make it easier to handle the pain; don’t be one of those people. Alcohol is a blood thinner, meaning you will bleed more and the ink won’t take as easily. Your constant drunken movements will also make the process take longer and the end result will be lackluster. Also try to avoid Tylenol, Advil, coffee, and energy drinks before your tattoo session, as they have similar effects.

Drinking water is a good idea, as well-hydrated skin accepts the ink more readily, so start drinking as much water as you need a day or two before. Taking breaks also helps, but try to take them sparingly, as the skin will begin to swell a lot more during your breaks and constant starting and stopping will interrupt a lot of the tattoo process and adrenaline build-up.

So if you’re looking to get a tattoo, either to celebrate your religion or to show off your lineage, or to simply some cool new artwork on your skin, now you know why it has to hurt and how you can make it hurt less; you can also pass the time being thankful you’re not getting crushed bug eggs rubbed into your wounds. Happy inking!

Wireless implants can block or induce the sensation of pain

Researchers at the Washington University School of Medicine, St. Louis and University of Illinois at Urbana-Champaign have developed implantable devices that can activate — and in theory, block too — pain signals traveling from the body through the spinal cord before they reach the brain.

The devices are controlled through wireless technology and have huge application in the treatment of chronic pain in parts of the body that don’t respond to other types of treatment. The full study has been published in the journal Nature Biotechnology.

Implanted microLED devices light up, activating peripheral nerve cells in mice.
Image via phys

“Our eventual goal is to use this technology to treat pain in very specific locations by providing a kind of ‘switch’ to turn off the pain signals long before they reach the brain,” said co-senior author Robert W. Gereau IV, PhD, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology and director of the Washington University Pain Center.

The devices are soft and stretchable so they can be implanted into any part of the body, Gereau explains. Previously, similar devices had to be anchored to bone tissue and proved problematic with limbs or other movable body parts.

“But when we’re studying neurons in the spinal cord or in other areas outside of the central nervous system, we need stretchable implants that don’t require anchoring,” he said.

The implants are sutured in place, and each boasts a microLED light that can activate specific neurons. The team behind them hopes to use the implants to blunt pain signals in patients who have pain that cannot be managed with standard therapies.

Experiments with genetically engineered mice (that were given light-sensitive proteins in some of their nerve cells) showed great promise for the devices. To demonstrate that the implants could influence the pain pathway in nerve cells, researchers induced a pain response. The mice were placed in a maze and as they walked through a specific area, the devices lit up and caused the little rodents to feel discomfort. When they left the area, the devices turned off, and the animals quickly learned to avoid the pain inducing part of the maze.

The experiment would have been very difficult with older optogenetic devices, which are tethered to a power source and can inhibit the movement of the mice.

As the new devices are smaller than those previously available, flexible and can be sutured in place, they have potential uses bladder, stomach, intestines, heart or other organs.

“They provide unique, biocompatible platforms for wireless delivery of light to virtually any targeted organ in the body,” he said.

Rogers and Gereau designed the implants with an eye toward manufacturing processes that would allow for mass production so the devices could be available to other researchers. Gereau, Rogers and Michael R. Bruchas, PhD, associate professor of anesthesiology at Washington University, have launched a company called NeuroLux to aid in that goal.