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Nerve-mimicking device gives ‘feeling’ to prosthetics

By Claudia López Lloreda When someone loses a hand or leg, they don’t just lose the ability to grab objects or walk—they lose the ability to touch and sense their surroundings. Prosthetics can restore some motor control, but they typically can’t restore sensation. Now, a preliminary studyposted to the preprint server bioRxiv this month—shows that by mimicking the activity of nerves, a device implanted in the remaining part of the leg helps amputees “feel” as they walk, allowing them to move faster and with greater confidence. “It's a really elegant study,” says Jacob George, neuroengineer at the University of Utah who was not involved with the research. Because the experiments go from a computational model to an animal model and then, finally humans, he says, “This work is really impactful, because it's one of the first studies that's done in a holistic way.” Patients with prosthetics often have a hard time adapting. One big issue is that they can’t accurately control the device because they can’t feel the pressure that they’re exerting on an object. Hand and arm amputees, for example, are more prone to drop or break things. As a result, some amputees refuse to use such prosthetics. In the past few years, researchers have been working on prosthetic limbs that provide more natural sensory feedback both to help control the device better and give them back a sense of agency over their robotic limb. In a critical study in 2019, George and his team showed that so-called biomimetic feedback, sensory information that aims to resemble the natural signals that occur with touch, allowed a patient who’d lost his hand to more precisely grip fragile objects such as eggs and grapes. But such studies have been limited to single patients. They’ve also left many questions unanswered about how exactly this feedback helps with motor control and improves the use of the prosthetic. So in the new work, researchers used a computer model that re-creates how nerves in the foot respond to different inputs, such as feeling pressure. The goal was to create natural patterns of neural activity that might occur when sensing something with the foot or walking. © 2023 American Association for the Advancement of Science.

Related chapters from BN: Chapter 8: General Principles of Sensory Processing, Touch, and Pain; Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 5: The Sensorimotor System
Link ID: 28863 - Posted: 08.02.2023

How the placebo effect went mainstream

By Charlotte Stoddart Charlotte Stoddart: Can a sugar pill make you feel better? What about the rituals surrounding a visit to the doctor? Can the care of a doctor or your trust in them reduce the amount of pain you feel? I’m Charlotte Stoddart and this is Knowable. This episode is all about the placebo effect. We’re going to look in detail at one key paper to learn how the placebo effect has been used in medicine and how it’s been understood and misunderstood. The paper is called “The Powerful Placebo.” It was written by Henry Beecher and published in JAMA, the Journal of the American Medical Association, in 1955. I chose this paper because it’s often referred to as a classic, and it’s still one of the most frequently cited papers on the placebo effect. I’ve enlisted the help of Ted Kaptchuk, who knows the paper well. Ted Kaptchuk: I enjoyed rereading it, actually. It’s a remarkable paper. I’ve read it probably 15 times in my life. Charlotte Stoddart: Ted is director of the Program in Placebo Studies at the Beth Israel Deaconess Medical Center in Boston and a professor of medicine at Harvard Medical School, where Henry Beecher also held a professorship. Beecher also worked at Massachusetts General Hospital. Charlotte Stoddart: During the Second World War, Beecher served in the US Army, and there’s a story about how that experience got him interested in the placebo effect. It goes like this: Beecher was working at a military hospital. One day, a badly injured soldier needed surgery, but the hospital had run out of morphine. So Beecher injected the soldier with saline solution instead. The soldier relaxed and Beecher carried out the operation without any real anesthetic. This, so the story goes, is when Beecher realized the power of the mind over the body. There are several different versions of this story, but Ted says it’s likely some version of it is true. © 2023 Annual Reviews

Related chapters from BN: Chapter 8: General Principles of Sensory Processing, Touch, and Pain; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 28832 - Posted: 06.28.2023

Brain implants have revealed a signature for chronic pain

By Laura Sanders Scientists can see chronic pain in the brain with new clarity. Over months, electrodes implanted in the brains of four people picked up specific signs of their persistent pain. This detailed view of chronic pain, described May 22 in Nature Neuroscience, suggests new ways to curtail the devastating condition. The approach “provides a way into the brain to track pain,” says Katherine Martucci, a neuroscientist who studies chronic pain at Duke University School of Medicine. Chronic pain is incredibly common. In the United States from 2019 to 2020, more adults were diagnosed with chronic pain than with diabetes, depression or high blood pressure, researchers reported May 16 in JAMA Network Open. Chronic pain is also incredibly complex, an amalgam influenced by the body, brain, context, emotions and expectations, Martucci says. That complexity makes chronic pain seemingly invisible to an outsider, and very difficult to treat. One treatment approach is to stimulate the brain with electricity. As part of a clinical trial, researchers at the University of California, San Francisco implanted four electrode wires into the brains of four volunteers with chronic pain. These electrodes can both monitor and stimulate nerve cells in two brain areas: the orbitofrontal cortex, or OFC, and the anterior cingulate cortex, or ACC. The OFC isn’t known to be a key pain influencer in the brain, but this region has lots of neural connections to pain-related areas, including the ACC, which is thought to be involved in how people experience pain. But before researchers stimulated the brain, they needed to know how chronic pain was affecting it. For about 3 to 6 months, the implanted electrodes monitored brain signals of these people as they went about their lives. During that time, the participants rated their pain on standard scales two to eight times a day. © Society for Science & the Public 2000–2023.

Scientists Find Brain Signals of Chronic Pain

By Priyanka Runwal Researchers have for the first time recorded the brain’s firing patterns while a person is feeling chronic pain, paving the way for implanted devices to one day predict pain signals or even short-circuit them. Using a pacemaker-like device surgically placed inside the brain, scientists recorded from four patients who had felt unremitting nerve pain for more than a year. The devices recorded several times a day for up to six months, offering clues for where chronic pain resides in the brain. The study, published on Monday in the journal Nature Neuroscience, reported that the pain was associated with electrical fluctuations in the orbitofrontal cortex, an area involved in emotion regulation, self-evaluation and decision making. The research suggests that such patterns of brain activity could serve as biomarkers to guide diagnosis and treatment for millions of people with shooting or burning chronic pain linked to a damaged nervous system. “The study really advances a whole generation of research that has shown that the functioning of the brain is really important to processing and perceiving pain,” said Dr. Ajay Wasan, a pain medicine specialist at the University of Pittsburgh School of Medicine, who wasn’t involved in the study. About one in five American adults experience chronic pain, which is persistent or recurrent pain that lasts longer than three months. To measure pain, doctors typically rely on patients to rate their pain, using either a numerical scale or a visual one based on emojis. But self-reported pain measures are subjective and can vary throughout the day. And some patients, like children or people with disabilities, may struggle to accurately communicate or score their pain. “There’s a big movement in the pain field to develop more objective markers of pain that can be used alongside self-reports,” said Kenneth Weber, a neuroscientist at Stanford University, who was not involved in the study. In addition to advancing our understanding of what neural mechanisms underlie the pain, Dr. Weber added, such markers can help validate the pain experienced by some patients that is not fully appreciated — or is even outright ignored — by their doctors. © 2023 The New York Times Company

Soft ‘Electronic skin’ mimics our sense of touch

Katharine Sanderson Researchers have developed an electronic skin that can mimic the same process that causes a finger, toe or limb to move when poked or scalded. The technology could lead to the development of a covering for prosthetic limbs that would give their wearers a sense of touch, or help to restore sensation in people whose skin has been damaged. The ‘e-skin’ was developed in the laboratory of chemical engineer Zhenan Bao at Stanford University in California. Her team has long been trying to make a prosthetic skin that is soft and flexible, but that can also transmit electrical signals to the brain to allow the wearer to ‘feel’ pressure, strain or changes in temperature. The latest work, published on 18 May in Science1, describes a thin, flexible sensor that can transmit a signal to part of the motor cortex in a rat’s brain that causes the animal’s leg to twitch when the e-skin is pressed or squeezed. “This current e-skin really has all the attributes that we have been dreaming about,” says Bao. “We have been talking about it for a long time.” In healthy living skin, mechanical receptors sense information and convert it into electrical pulses that are transmitted through the nervous system to the brain. To replicate this, an electronic skin needs sensors and integrated circuits, which are usually made from rigid semiconductors. Flexible electronic systems are already available, but they typically work only at high voltages that would be unsafe for wearable devices. To make a fully soft e-skin, Bao’s team developed a flexible polymer for use as a dielectric — a thin layer in a semiconductor device that determines the strength of the signal and the voltage needed to run the device. The researchers then used the dielectric to make stretchy, flexible arrays of transistors, combined into a sensor that was thin and soft like skin. © 2023 Springer Nature Limited

Related chapters from BN: Chapter 8: General Principles of Sensory Processing, Touch, and Pain
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 28790 - Posted: 05.21.2023

Chronic pain: the long road to discovery

By Lucy Odling-Smee Philip Kass spends 90% of his day lying on a twin bed in a sparsely decorated room that used to belong to his niece. He takes most meals with a plate balanced on his chest, and he usually watches television because reading is too stressful. “I’m barely living,” he told me on a warm night in June last year. Ever since a back injury 23 years ago, pain has been eating away at Kass’s life. It has cost him his career, his relationships, his mobility and his independence. Now 55, Kass lives with his sister and her family in San Francisco, California. He occasionally joins them for dinner, which means he’ll eat while standing. And once a day he tries to walk four or five blocks around the neighbourhood. But he worries that any activity, walking too briskly or sitting upright for more than a few minutes, will trigger a fresh round of torment that can take days or weeks to subside. Philip Kass has dealt with pain for more than two decades. Some of what Kass describes is familiar. I have been pinned to the floor by spinal pain several times in my life. In my twenties, I was immobilized for three months. In my thirties and forties, each episode of severe pain lasted more than a year. I spent at least another half decade standing or pacing through meetings, meals and movies — for fear that even a few minutes spent sitting would result in weeks of disabling pain. For years, I read anything I could find to better understand why my pain persisted.

F.D.A. Approves New Nasal Spray for Migraines

By Christina Jewett The Food and Drug Administration has approved a Pfizer nasal spray for treatment of migraines that uses a different therapy from other nasal products on the market for severe headache pain, the company said on Friday. The fast-acting treatment, which is called zavegepant and will be sold as Zavzpret, performed better than a placebo in relieving pain and patients’ most bothersome symptoms, according to clinical trial results published in the journal Lancet Neurology. Participants in the trial who took the medication were more likely to report returning to normal function 30 minutes to two hours after taking it. The gains, though, were not significant for every patient. A study tracked the experience of 1,269 patients — half on the drug and half on a placebo — focusing on how they reported feeling two hours after using either substance. About 24 percent on the medication reported freedom from pain, compared to about 15 percent who took a placebo, according to the study. Dr. Timothy A. Collins, chief of the headache division at Duke University Medical Center’s neurology department, said the product gave doctors a new option in a nasal spray format that patients with migraines tended to appreciate. He said the condition often comes with nausea, so swallowing a pill can be unpleasant. He also said the drug presented few side effects, like drowsiness, that had been reported with other products. “We’ve been waiting for this medication to come out,” Dr. Collins said. “It’s a really helpful addition to migraine management.” One additional upside of the medication is that it’s safe for patients who have had a heart attack or a stroke, he added. Pfizer said the medication would be available in pharmacies in July, but did not disclose the estimated price of the new spray. The company estimated that nearly 40 million people in the United States suffered from migraines each year. © 2023 The New York Times Company

Neuronal Scaffolding Plays Unexpected Role in Pain

R. Douglas Fields Neuroscientists, being interested in how brains work, naturally focus on neurons, the cells that can convey elements of sense and thought to each other via electrical impulses. But equally worthy of study is a substance that’s between them — a viscous coating on the outside of these neurons. Roughly equivalent to the cartilage in our noses and joints, the stuff clings like a fishing net to some of our neurons, inspiring the name perineuronal nets (PNNs). They’re composed of long chains of sugar molecules attached to a protein scaffolding, and they hold neurons in place, preventing them from sprouting and making new connections. Given this ability, this little-known neural coating provides answers to some of the most puzzling questions about the brain: Why do young brains absorb new information so easily? Why are the fearful memories that accompany post-traumatic stress disorder (PTSD) so difficult to forget? Why is it so hard to stop drinking after becoming dependent on alcohol? And according to new research from the neuroscientist Arkady Khoutorsky and his colleagues at McGill University, we now know that PNNs also explain why pain can develop and persist so long after a nerve injury. Neural plasticity is the ability of neural networks to change in response to experiences in life or to repair themselves after brain injury. Such opportunities for effortless change are known as critical periods when they occur early in life. Consider how easily babies pick up language, but how difficult it is to learn a foreign language as an adult. In a way, this is what we’d want: After the intricate neural networks that allow us to understand our native language are formed, it’s important for them to be locked down, so the networks remain relatively undisturbed for the rest of our lives. All Rights Reserved © 2022

Bees may feel pain

ByVirginia Morell We swat bees to avoid painful stings, but do they feel the pain we inflict? A new study suggests they do, a possible clue that they and other insects have sentience—the ability to be aware of their feelings. “It’s an impressive piece of work” with important implications, says Jonathan Birch, a philosopher and expert on animal sentience at the London School of Economics who was not involved with the paper. If the study holds up, he says, “the world contains far more sentient beings than we ever realized.” Previous research has shown honey bees and bumble bees are intelligent, innovative, creatures. They understand the concept of zero, can do simple math, and distinguish among human faces (and probably bee faces, too). They’re usually optimistic when successfully foraging, but can become depressed if momentarily trapped by a predatory spider. Even when a bee escapes a spider, “her demeanor changes; for days after, she’s scared of every flower,” says Lars Chittka, a cognitive scientist at Queen Mary University of London whose lab carried out that study as well as the new research. “They were experiencing an emotional state.” To find out whether these emotions include pain, Chittka and colleagues looked at one of the criteria commonly used for defining pain in animals: “motivational trade-offs.” People will endure the pain of a dentist’s drill for the longer term benefits of healthy teeth, for example. Similarly, hermit crabs will leave preferred shells to escape an electric shock only when given a particularly high jolt—an experiment that demonstrated crabs can tell the difference between weak and strong painful stimuli, and decide how much pain is worth enduring. That suggests crabs do feel pain and don’t simply respond reflexively to an unpleasant stimulus. Partly as a result of that study, crabs (and other crustaceans, including lobsters and crayfish) are recognized as sentient under U.K. law. © 2022 American Association for the Advancement of Science

Related chapters from BN: Chapter 8: General Principles of Sensory Processing, Touch, and Pain; Chapter 6: Evolution of the Brain and Behavior
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 28410 - Posted: 07.30.2022

This soft, electronic ‘nerve cooler’ could be a new way to relieve pain

By Meghan Rosen A flexible electronic implant could one day make pain management a lot more chill. Created from materials that dissolve in the body, the device encircles nerves with an evaporative cooler. Implanted in rats, the cooler blocked pain signals from zipping up to the brain, bioengineer John Rogers and colleagues report in the July 1 Science. Though far from ready for human use, a future version could potentially let “patients dial up or down the pain relief they need at any given moment,” says Rogers, of Northwestern University in Evanston, Ill. Scientists already knew that low temperatures can numb nerves in the body. Think of frozen fingers in the winter, Rogers says. But mimicking this phenomenon with an electronic implant isn’t easy. Nerves are fragile, so scientists need something that gently hugs the tissues. And an ideal implant would be absorbed by the body, so doctors wouldn’t have to remove it. Made from water-soluble materials, the team’s device features a soft cuff that wraps around a nerve like toilet paper on a roll. Tiny channels snake down its rubbery length. When liquid coolant that’s pumped through the channels evaporates, the process draws heat from the underlying nerve. A temperature sensor helps scientists hit the sweet spot — cold enough to block pain but not too cold to damage the nerve. The researchers wrapped the implant around a nerve in rats and tested how they responded to having a paw poked. With the nerve cooler switched on, scientists could apply about seven times as much pressure as usual before the animals pulled their paws away. That’s a sign that the rats’ senses had grown sluggish, Rogers says. © Society for Science & the Public 2000–2022.

Seals use whiskers to track prey in deep ocean

Sofia Quaglia When they are in the deep, dark ocean, seals use their whiskers to track down their prey, a study has confirmed after observing the sea mammals in their natural habitat. It’s hard for light to penetrate the gloom of the ocean’s depths, and animals have come up with a variety of adaptations in order to live and hunt there. Whales and dolphins, for example, use echolocation – the art of sending out clicky noises into the water and listening to their echo as they bounce off possible prey, to locate them. But deep-diving seals who don’t have those same acoustic projectors must have evolutionarily learned to deploy another sensory technique. Scientists have long hypothesised that the secret weapons are their long, cat-like whiskers, conducting over 20 years of experiments with artificial whiskers or captive seals blindfolded in a pool, given the difficulties of directly observing the hunters in the tenebrous depths of the ocean. Now a study may have confirmed the hypothesis, according to Taiki Adachi, assistant project scientist of University of California, Santa Cruz, and one of the lead authors of the study published in Proceedings of the National Academy of Science. Adachi and his team positioned small video cameras with infrared night-vision on the left cheek, lower jaw, back and head of five free-ranging northern elephant seals, the Mirounga angustirostris, in Año Nuevo state park in California. They recorded a total of approximately nine and a half hours of deep sea footage during their seasonal migration. By analysing the videos the scientists noted that diving seals held back their whiskers for the initial part of their dives and, and once they reached a depth suitable for foraging, they rhythmically whisked their whiskers back and forth, hoping to sense any vibration caused by the slightest water movements of swimming prey. © 2022 Guardian News & Media Limited o

Scientists grew living human skin around a robotic finger

By Maria Temming The Terminator may be one step closer to reality. Researchers at the University of Tokyo have built a robotic finger that, much like Arnold Schwarzenegger’s titular cyborg assassin, is covered in living human skin. The goal is to someday build robots that look like real people — albeit for more altruistic applications. Super realistic-looking robots could more seamlessly interact with humans in medical care and service industries, say biohybrid engineer Shoji Takeuchi and his colleagues June 9 in Matter. (Whether cyborgs masked in living tissue would be more congenial or creepy is probably in the eye of the beholder.) To cover the finger in skin, Takeuchi and colleagues submerged the robotic digit in a blend of collagen and human skin cells called dermal fibroblasts. The mixture settled into a base layer of skin, or dermis, covering the finger. The team then poured a liquid containing human keratinocyte cells onto the finger, which formed an outer skin layer, or epidermis. After two weeks, skin covering the finger measured a few millimeters thick — comparable to the thickness of human skin. The lab-made skin was strong and stretchy enough to withstand the robotic finger bending. It could also heal itself: When researchers made a small cut on the robotic finger and covered it with a collagen bandage, the skin’s fibroblast cells merged the bandage with the rest of the skin within a week. Researchers at the University of Tokyo covered this robotic finger in living human skin to pave the way for ultrarealistic cyborgs. “This is very interesting work and an important step forward in the field,” says Ritu Raman, an MIT engineer who also builds machines with living components. “Biological materials are appealing because they can dynamically sense and adapt to their environments.” For instance, she’d like to see a future version of the living robot skin embedded with nerve cells to make robots more aware of their surroundings. © Society for Science & the Public 2000–2022.

Common Medications Can Prolong Back Pain

By Gina Kolata The very treatments often used to soothe pain in the lower back, which the Centers for Disease Control and Prevention says is the most common type of pain, might cause it to last longer, according to a new study. Managing pain with steroids and nonsteroidal anti-inflammatory drugs, like ibuprofen, can actually turn a wrenched back into a chronic condition, the study found. Some medical experts urged caution in interpreting the results too broadly. The study did not use the gold standard for medical research, which would be a clinical trial in which people with back pain would be randomly assigned to take a nonsteroidal anti-inflammatory drug or a placebo and followed to see who developed chronic pain. Instead, it involved observations of patients, an animal study and an analysis of patients in a large database. “It’s intriguing but requires further study,” said Dr. Steven J. Atlas, director of primary care practice-based research and quality improvement at Massachusetts General Hospital. Dr. Bruce M. Vrooman, a pain specialist at Dartmouth Hitchcock Medical Center in New Hampshire, agreed, but also called the study “impressive in its scope” and said that if the results hold up in a clinical trial, it could “force reconsideration of how we treat acute pain.” Dr. Thomas Buchheit, director of the regenerative pain therapies program at Duke, had a different view. “People overuse the term ‘paradigm shift’, but this is absolutely a paradigm shift,” Dr. Buchheit said. “There is this unspoken rule: If it hurts, take an anti-inflammatory, and if it still hurts, put a steroid on it,” he added. “But,” he said, the study shows that “we have to think of healing and not suppression of inflammation.” Guidelines from professional medical societies already say that people with back pain should start with nondrug treatments like exercise, physical therapy, heat or massage. Those measures turn out to be as effective as pain-suppressing drugs, without the same side effects. © 2022 The New York Times Company

Nerve blocks may help counter the opioid crisis

Perspective by Susan Berger As I faced a prophylactic double mastectomy in hopes of averting cancer, I had many questions for my surgeons — one of which was about pain. I was stunned when both my breast surgeon and plastic surgeon said that a nerve block would leave me pain-free for about three days, after which the worst of the pain would be over. Pectoralis nerve (PECS) blocks were developed to provide analgesia or pain relief for chest surgeries, including breast surgery. That is what happened. I went through the mastectomy Dec. 1 after learning I had the PALB2 gene mutation that carried a sharply elevated risk of breast cancer as well as a higher risk of ovarian and pancreatic cancers. I also had my fallopian tubes and ovaries removed in July. I had learned about the gene mutation in April 2021, when one of my daughters found out she was a carrier. As a 24-year breast cancer survivor and longtime health reporter, I was astonished that I had heard nothing about this mutation. I researched it and wrote “This Breast Cancer Gene Is Less Well Known, but Nearly as Dangerous” in August. After the double mastectomy, I also wrote about it for The Washington Post. Just as my surgeons at NorthShore University HealthSystem predicted, I was released from the hospital the same day as my surgery and remarkably pain-free. I took one Tramadol (a step down from stronger medications containing codeine) when I got home — only because it was suggested I take one pill. As I recovered, I only took Advil and Tylenol. The opioid epidemic is a major public health issue in the United States and nerve blocks could be a solution. According to a study published in the Journal of Clinical Medicine in 2021, 1 in 20 surgical patients will continue to use opioids beyond 90 days. “There is no association with magnitude of surgery, major versus minor, and the strongest predictor of continued use is surgical exposure,” the study states. © 1996-2022 The Washington Post

Related chapters from BN: Chapter 8: General Principles of Sensory Processing, Touch, and Pain; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 4: Development of the Brain
Link ID: 28316 - Posted: 05.07.2022

Deadly Venom From Spiders and Snakes May Cure What Ails You

By Jim Robbins TUCSON, Ariz. — In a small room in a building at the Arizona-Sonora Desert Museum, the invertebrate keeper, Emma Califf, lifts up a rock in a plastic box. “This is one of our desert hairies,” she said, exposing a three-inch-long scorpion, its tail arced over its back. “The largest scorpion in North America.” This captive hairy, along with a swarm of inch-long bark scorpions in another box, and two dozen rattlesnakes of varying species and sub- species across the hall, are kept here for the coin of the realm: their venom. Efforts to tease apart the vast swarm of proteins in venom — a field called venomics — have burgeoned in recent years, and the growing catalog of compounds has led to a number of drug discoveries. As the components of these natural toxins continue to be assayed by evolving technologies, the number of promising molecules is also growing. “A century ago we thought venom had three or four components, and now we know just one type of venom can have thousands,” said Leslie V. Boyer, a professor emeritus of pathology at the University of Arizona. “Things are accelerating because a small number of very good laboratories have been pumping out information that everyone else can now use to make discoveries.” She added, “There’s a pharmacopoeia out there waiting to be explored.” It is a striking case of modern-day scientific alchemy: The most highly evolved of natural poisons on the planet are creating a number of effective medicines with the potential for many more. One of the most promising venom-derived drugs to date comes from the deadly Fraser Island funnel web spider of Australia, which halts cell death after a heart attack. Blood flow to the heart is reduced after a heart attack, which makes the cell environment more acidic and leads to cell death. The drug, a protein called Hi1A, is scheduled for clinical trials next year. In the lab, it was tested on the cells of beating human hearts. It was found to block their ability to sense acid, “so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” said Nathan Palpant, a researcher at the University of Queensland in Australia who helped make the discovery. © 2022 The New York Times Company

Why do antidepressants help with nerve pain relief?

Ellen Phiddian Tricyclic antidepressants have long been known to have more than one purpose: among other things, they can alleviate pain – particularly nerve pain. Recent research has finally established why these tricyclic antidepressants (TCAs) can help with nerve pain. The discovery could lead to the rapid development of pain relief medications that don’t include the side effects of TCAs. Nerve pain comes from a variety of sources – including cancer, diabetes, trauma, multiple sclerosis, and infections. These treatments could address a range of different types of nerve pain. It turns out the drugs inhibit a key protein in our nerves, called an N-type calcium channel. These N-type calcium channels are shaped like tiny gates, allowing positively charged calcium ions, or Ca2+, through them. This helps with the transmission of pain signals in the body. Researchers have long been keen to find things that “close” the gate of these calcium channels because that’s likely to have analgesic effects. Adjunct Professor Peter Duggan, a researcher with the CSIRO and senior collaborator on the project, says that he and his colleagues initially stumbled across TCAs from a very different direction: they were investigating the toxins of venomous marine cone snails. “A few of the components in that toxin are actually painkillers and they block these calcium ion channels very, very effectively,” says Duggan. The cone snail toxin has the potential to be very dangerous to people, as well as needing to be administered in an impractical way, so the researchers started looking at similar compounds that might have some of the same properties.

Can Virtual Reality Help Ease Chronic Pain?

By Helen Ouyang After an hour-and-a-half bus ride last November, Julia Monterroso arrived at a white Art Deco building in West Hollywood, just opposite a Chanel store and the Ivy, a restaurant famous for its celebrity sightings. Monterroso was there to see Brennan Spiegel, a gastroenterologist and researcher at Cedars-Sinai who runs one of the largest academic medical initiatives studying virtual reality as a health therapy. He started the program in 2015 after the hospital received a million-dollar donation from an investment banker on its board. Spiegel saw Monterroso in his clinic the week before and thought he might be able to help alleviate her symptoms. Monterroso is 55 and petite, with youthful bangs and hair clipped back by tiny jeweled barrettes. Eighteen months earlier, pain seized her lower abdomen and never went away. After undergoing back surgery in September to treat a herniated disc — and after the constant ache in her abdomen worsened — she had to stop working as a housecleaner. Eventually, following a series of tests that failed to reveal any clear cause, she landed in Spiegel’s office. She rated her pain an 8 on a 10-point scale, with 10 being the most severe. Chronic pain is generally defined as pain that has lasted three months or longer. It is one of the leading causes of long-term disability in the world. By some measures, 50 million Americans live with chronic pain, in part because the power of medicine to relieve pain remains woefully inadequate. As Daniel Clauw, who runs the Chronic Pain and Fatigue Research Center at the University of Michigan, put it in a 2019 lecture, there isn’t “any drug in any chronic-pain state that works in better than one out of three people.” He went on to say that nonpharmacological therapy should instead be “front and center in managing chronic pain — rather than opioids, or for that matter, any of our drugs.” Virtual reality is emerging as an unlikely tool for solving this intractable problem. The V.R. segment in health care alone, which according to some estimates is already valued at billions of dollars, is expected to grow by multiples of that in the next few years, with researchers seeing potential for it to help with everything from anxiety and depression to rehabilitation after strokes to surgeons strategizing where they will cut and stitch. In November, the Food and Drug Administration gave authorization for the first V.R. product to be marketed for the treatment of chronic pain. © 2022 The New York Times Company

Related chapters from BN: Chapter 8: General Principles of Sensory Processing, Touch, and Pain; Chapter 10: Vision: From Eye to Brain
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 7: Vision: From Eye to Brain
Link ID: 28304 - Posted: 04.27.2022

Doctor accused of killing 14 patients with fentanyl acquitted of murder

By Brittany Shammas and Timothy Bella William Husel, an Ohio doctor who was accused of killing 14 patients with what prosecutors described as “wildly excessive” doses of fentanyl between 2015 and 2018, was acquitted on all counts of murder Wednesday, concluding one of the most significant murder cases of its kind against a health-care professional. Husel, a onetime physician of the year trained at the Cleveland Clinic, faced one count of murder for each of the 14 critically ill patients he was accused of killing. The jury deliberated for seven days before finding him not guilty on all 14 counts in what was one of the largest murder trials in Ohio history. He had been charged with causing or hastening their deaths amid a period of lax oversight of fentanyl at Mount Carmel West, a Catholic hospital in Columbus. Husel would have faced life in prison with just one guilty verdict. While the synthetic opioid is significantly more powerful than morphine and has wreaked havoc on American streets, it can provide pain relief in medical settings that is crucial to end-of-life care. The alleged victims in the Ohio case suffered critical medical conditions including overdoses, cancer, strokes and internal bleeding. Prosecutors acknowledged that all were being kept alive on ventilators and that many of them were dying. “In truth, William Husel was an innocent man, and thank goodness the justice system prevailed,” Jose Baez, one of Husel’s defense attorneys, told reporters. The 46-year-old’s acquittal came after a two-month trial that triggered a debate on end-of-life medical care. Husel and Baez argued in the trial that the doctor offered comfort care for dying patients and was not trying to kill them. They pointed out that the doctor’s actions did not occur in secret — nurses were the ones to administer the doses — and alleged that hospital officials made Husel the villain after realizing the systemic failures at play. The fallout over the allegations at Mount Carmel West had repercussions: the firing of 23 employees; the resignation of the hospital’s chief executive, chief clinical officer and chief pharmacy officer; and Medicare and Medicaid funding for the institution was put in jeopardy. © 1996-2022 The Washington Post

Non-opioid pain pill shows promise in clinical trials

ByKelly Servick An experimental pain drug that may offer an alternative to opioids has shown promise in two small clinical trials for acute pain, its developer announced today. Vertex Pharmaceuticals’s compound, called VX-548, outperformed a placebo in phase 2 trials for two types of postsurgical pain, the company said in a press release. The results pave the way for larger trials that could lead to regulatory approval. “This is a major advance in the effort to supersede opioids,” says John Wood, a neurobiologist at University College London who has studied the cellular channel that VX-548 targets. “These results are terrific, and the side effect profile is very good.” Opioids are powerful pain relievers, but they can cause side effects including slowed breathing, and they come with the potential for addiction. An epidemic of overdose deaths has prompted a hunt for safer alternatives. The new trials grew out of research into sodium channels on the surface of pain-sensing neurons, which let them fire electrical signals. One such channel, called Nav1.8, is crucial to relaying pain signals to the spinal cord from nerves throughout the body. People with genetic mutations that make Nav1.8 hyperactive can suffer pain even in the absence of injury. But relieving pain by blocking either Nav1.8 or another channel, Nav1.7, has proved difficult. One issue is their structure closely resembles those of other sodium channels, which regulate vital functions in the heart, muscles, and brain. To be safe, a compound needs to target the channel of interest and not accidentally target these other, critical channels. Vertex has spent years developing highly specific Nav1.8-blocking drugs, but it has abandoned previous candidates before they reached pivotal phase 3 trials. One drug, known as VX-150, succeeded in three phase 2 clinical studies but never advanced to larger ones, in part because its high dose might be impractical for clinical use. “We wanted to have higher potency,” explains Vertex Chief Scientific Officer David Altshuler. © 2022 American Association for the Advancement of Science.

For Decades, He Had Strange Episodes of Utter Exhaustion

By Lisa Sanders, M.D. The 51-year-old man sat at his desk preparing for his next online meeting when he suddenly became aware of a familiar stiffness and exhaustion. Had he slept badly? Or was this the beginning of one of his strange episodes? As the symptoms worsened, he had his answer. He knew that when he started to feel this way, the only recourse was to get into bed before he got any weaker. As he made his way slowly down the hall, his legs felt heavy, as if he were wearing ankle weights. Just lifting them was real work. He passed his wife’s home office without a word. She knew just from looking at him that he would probably have to spend the rest of the day in bed. For much of their 30-year marriage, he had these strange spells; he would suddenly feel exhausted and weak and have to lie down. He couldn’t work. He was a software engineer, and any mental exertion was too much for him. Once the fatigue fully set in — maybe after the first hour or so — he couldn’t walk, couldn’t stand, couldn’t even sit up. It was as if his body was totally out of gas, worse than how it felt when he ran a marathon. He would lie in a dark room, too weak to even hold up a book and too tired to think. But by the next morning, he would usually be fine, brimming with energy and enthusiasm, like normal. It was so strange. After more than 20 years, they both had come to expect these episodes. For most of that time, the spells were infrequent, maybe once a month. But recently they became more frequent. The monthly episodes became weekly, then a couple of times a week. They often came, as they did that morning, out of nowhere. Just before leaving his office, he sent an email to the woman he was to meet online. Sorry, he wrote, I’m not feeling well. Could we reschedule? Seeing a Psychiatrist Over the years the man saw many doctors. They had their theories, but so far none panned out. A few were convinced that he had periodic paralysis, a disorder sometimes linked to thyroid disease, where patients become temporarily paralyzed by too much or too little potassium in the bloodstream. But his potassium was always normal, even during these episodes. © 2022 The New York Times Company

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