Pooja Shree Chettiar, Texas A&M University and Siddhesh Sabnis, Texas A&M University

Pain is easy to understand until it isn’t. A stubbed toe or sprained ankle hurts, but it makes sense because the cause is clear and the pain fades as you heal.

But what if the pain didn’t go away? What if even a breeze felt like fire, or your leg burned for no reason at all? When pain lingers without a clear cause, that’s neuropathic pain.

We are neuroscientists who study how pain circuits in the brain and spinal cord change over time. Our work focuses on the molecules that quietly reshape how pain is felt and remembered.

We didn’t fully grasp how different neuropathic pain was from injury-related pain until we began working in a lab studying it. Patients spoke of a phantom pain that haunted them daily – unseen, unexplained and life-altering.

These conversations shifted our focus from symptoms to mechanisms. What causes this ghost pain to persist, and how can we intervene at the molecular level to change it?

More than just physical pain

Neuropathic pain stems from damage to or dysfunction in the nervous system itself. The system that was meant to detect pain becomes the source of it, like a fire alarm going off without a fire. Even a soft touch or breeze can feel unbearable.

Neuropathic pain doesn’t just affect the body – it also alters the brain. Chronic pain of this nature often leads to depression, anxiety, social isolation and a deep sense of helplessness. It can make even the most routine tasks feel unbearable.

About 10% of the U.S. population – tens of millions of people – experience neuropathic pain, and cases are rising as the population ages. Complications from diabetes, cancer treatments or spinal cord injuries can lead to this condition. Despite its prevalence, doctors often overlook neuropathic pain because its underlying biology is poorly understood.

There’s also an economic cost to neuropathic pain. This condition contributes to billions of dollars in health care spending, missed workdays and lost productivity. In the search for relief, many turn to opioids, a path that, as seen from the opioid epidemic, can carry its own devastating consequences through addiction.

GluD1: A quiet but crucial player

Finding treatments for neuropathic pain requires answering several questions. Why does the nervous system misfire in this way? What exactly causes it to rewire in ways that increase pain sensitivity or create phantom sensations? And most urgently: Is there a way to reset the system?

This is where our lab’s work and the story of a receptor called GluD1 comes in. Short for glutamate delta-1 receptor, this protein doesn’t usually make headlines. Scientists have long considered GluD1 a biochemical curiosity, part of the glutamate receptor family, but not known to function like its relatives that typically transmit electrical signals in the brain.

Instead, GluD1 plays a different role. It helps organize synapses, the junctions where neurons connect. Think of it as a construction foreman: It doesn’t send messages itself, but directs where connections form and how strong they become.

This organizing role is critical in shaping the way neural circuits develop and adapt, especially in regions involved in pain and emotion. Our lab’s research suggests that GluD1 acts as a molecular architect of pain circuits, particularly in conditions like neuropathic pain where those circuits misfire or rewire abnormally. In parts of the nervous system crucial for pain processing like the spinal cord and amygdala, GluD1 may shape how people experience pain physically and emotionally.

Fixing the misfire

Across our work, we found that disruptions to GluD1 activity is linked to persistent pain. Restoring GluD1 activity can reduce pain. The question is, how exactly does GluD1 reshape the pain experience?

In our first study, we discovered that GluD1 doesn’t operate solo. It teams up with a protein called cerebellin-1 to form a structure that maintains constant communication between brain cells. This structure, called a trans-synaptic bridge, can be compared to a strong handshake between two neurons. It makes sure that pain signals are appropriately processed and filtered.

But in chronic pain, the bridge between these proteins becomes unstable and starts to fall apart. The result is chaotic. Like a group chat where everyone is talking at once and nobody can be heard clearly, neurons start to misfire and overreact. This synaptic noise turns up the brain’s pain sensitivity, both physically and emotionally. It suggests that GluD1 isn’t just managing pain signals, but also may be shaping how those signals feel.

What if we could restore that broken connection?

In our second study, we injected mice with cerebellin-1 and saw that it reactivated GluD1 activity, easing their chronic pain without producing any side effects. It helped the pain processing system work again without the sedative effects or disruptions to other nerve signals that are common with opioids. Rather than just numbing the body, reactivating GluD1 activity recalibrated how the brain processes pain.

Of course, this research is still in the early stages, far from clinical trials. But the implications are exciting: GluD1 may offer a way to repair the pain processing network itself, with fewer side effects and less risk of addiction than current treatments.

For millions living with chronic pain, this small, peculiar receptor may open the door to a new kind of relief: one that heals the system, not just masks its symptoms.

Pooja Shree Chettiar, Ph.D. Candidate in Medical Sciences, Texas A&M University and Siddhesh Sabnis, Ph.D. Student in Medical Sciences, Texas A&M University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Jennifer D. Oliva, Indiana University

Over the past decade, health insurance companies have increasingly embraced the use of artificial intelligence algorithms. Unlike doctors and hospitals, which use AI to help diagnose and treat patients, health insurers use these algorithms to decide whether to pay for health care treatments and services that are recommended by a given patient’s physicians.

One of the most common examples is prior authorization, which is when your doctor needs to
receive payment approval from your insurance company before providing you care. Many insurers use an algorithm to decide whether the requested care is “medically necessary” and should be covered.

These AI systems also help insurers decide how much care a patient is entitled to — for example, how many days of hospital care a patient can receive after surgery.

If an insurer declines to pay for a treatment your doctor recommends, you usually have three options. You can try to appeal the decision, but that process can take a lot of time, money and expert help. Only 1 in 500 claim denials are appealed. You can agree to a different treatment that your insurer will cover. Or you can pay for the recommended treatment yourself, which is often not realistic because of high health care costs.

As a legal scholar who studies health law and policy, I’m concerned about how insurance algorithms affect people’s health. Like with AI algorithms used by doctors and hospitals, these tools can potentially improve care and reduce costs. Insurers say that AI helps them make quick, safe decisions about what care is necessary and avoids wasteful or harmful treatments.

But there’s strong evidence that the opposite can be true. These systems are sometimes used to delay or deny care that should be covered, all in the name of saving money.

A pattern of withholding care

Presumably, companies feed a patient’s health care records and other relevant information into health care coverage algorithms and compare that information with current medical standards of care to decide whether to cover the patient’s claim. However, insurers have refused to disclose how these algorithms work in making such decisions, so it is impossible to say exactly how they operate in practice.

Using AI to review coverage saves insurers time and resources, especially because it means fewer medical professionals are needed to review each case. But the financial benefit to insurers doesn’t stop there. If an AI system quickly denies a valid claim, and the patient appeals, that appeal process can take years. If the patient is seriously ill and expected to die soon, the insurance company might save money simply by dragging out the process in the hope that the patient dies before the case is resolved.

This creates the disturbing possibility that insurers might use algorithms to withhold care for expensive, long-term or terminal health problems , such as chronic or other debilitating disabilities. One reporter put it bluntly: “Many older adults who spent their lives paying into Medicare now face amputation or cancer and are forced to either pay for care themselves or go without.”

Research supports this concern – patients with chronic illnesses are more likely to be denied coverage and suffer as a result. In addition, Black and Hispanic people and those of other nonwhite ethnicities, as well as people who identify as lesbian, gay, bisexual or transgender, are more likely to experience claims denials. Some evidence also suggests that prior authorization may increase rather than decrease health care system costs.

Insurers argue that patients can always pay for any treatment themselves, so they’re not really being denied care. But this argument ignores reality. These decisions have serious health consequences, especially when people can’t afford the care they need.

Moving toward regulation

Unlike medical algorithms, insurance AI tools are largely unregulated. They don’t have to go through Food and Drug Administration review, and insurance companies often say their algorithms are trade secrets.

That means there’s no public information about how these tools make decisions, and there’s no outside testing to see whether they’re safe, fair or effective. No peer-reviewed studies exist to show how well they actually work in the real world.

There does seem to be some momentum for change. The Centers for Medicare & Medicaid Services, or CMS, which is the federal agency in charge of Medicare and Medicaid, recently announced that insurers in Medicare Advantage plans must base decisions on the needs of individual patients – not just on generic criteria. But these rules still let insurers create their own decision-making standards, and they still don’t require any outside testing to prove their systems work before using them. Plus, federal rules can only regulate federal public health programs like Medicare. They do not apply to private insurers who do not provide federal health program coverage.

Some states, including Colorado, Georgia, Florida, Maine and Texas, have proposed laws to rein in insurance AI. A few have passed new laws, including a 2024 California statute that requires a licensed physician to supervise the use of insurance coverage algorithms.

But most state laws suffer from the same weaknesses as the new CMS rule. They leave too much control in the hands of insurers to decide how to define “medical necessity” and in what contexts to use algorithms for coverage decisions. They also don’t require those algorithms to be reviewed by neutral experts before use. And even strong state laws wouldn’t be enough, because states generally can’t regulate Medicare or insurers that operate outside their borders.

A role for the FDA

In the view of many health law experts, the gap between insurers’ actions and patient needs has become so wide that regulating health care coverage algorithms is now imperative. As I argue in an essay to be published in the Indiana Law Journal, the FDA is well positioned to do so.

The FDA is staffed with medical experts who have the capability to evaluate insurance algorithms before they are used to make coverage decisions. The agency already reviews many medical AI tools for safety and effectiveness. FDA oversight would also provide a uniform, national regulatory scheme instead of a patchwork of rules across the country.

Some people argue that the FDA’s power here is limited. For the purposes of FDA regulation, a medical device is defined as an instrument “intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease.” Because health insurance algorithms are not used to diagnose, treat or prevent disease, Congress may need to amend the definition of a medical device before the FDA can regulate those algorithms.

If the FDA’s current authority isn’t enough to cover insurance algorithms, Congress could change the law to give it that power. Meanwhile, CMS and state governments could require independent testing of these algorithms for safety, accuracy and fairness. That might also push insurers to support a single national standard – like FDA regulation – instead of facing a patchwork of rules across the country.

The move toward regulating how health insurers use AI in determining coverage has clearly begun, but it is still awaiting a robust push. Patients’ lives are literally on the line.

Jennifer D. Oliva, Professor of Law, Indiana University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Brian Bossak, College of Charleston

Beach trips, cookouts and other outdoor activities are in full swing as summer arrives and the first widespread heat wave of 2025 hits the U.S.

For many people, summer is their favorite time of year. However, summer also brings the risk of dangerously high temperatures.

In the U.S., hundreds of people working or playing outside – even those who seem healthy – succumb to heat-related illnesses each year. Older adults and people in areas that historically haven’t needed air conditioning tend to see the highest rates of illnesses during heat waves, as Chicago saw in 1995 when at least 700 people died in a heat wave.

Even in places where heat is recognized as a dangerous health threat, people can be caught off guard as the thermometer creeps higher, on average, each year. In some cases, dangerous heat can arise quickly. In 2021, a young family died of heat stroke on a California trail after setting out for a hike when temperatures were still in the 70s Fahrenheit (low to mid 20s Celsius).

I study health risks in a warming climate as a professor of public health, and I’ve seen heat become a growing concern. Here are some of the key warning signs to watch for when temperatures rise – and ways to keep cool when the heat and humidity get too high.

Signs of heat-related illness to watch for

Heat-related illnesses occur across a spectrum, and mild heat stress can quickly progress to life-threatening heat stroke if a person is exposed to dangerous conditions for too long.

Mild forms of heat-related illness include heat cramps and heat rash, both of which can be caused by extensive sweating during hot conditions. Cooling the body and drinking cool fluids can help.

When heat-related illnesses progress into heat exhaustion, the situation is more serious. Heat exhaustion includes symptoms such as dizziness, nausea, excessive sweating, feeling weak, thirst and getting a headache.

Heat exhaustion is a signal that the body is losing its ability to maintain a stable core temperature. Immediate action such as moving to a cool, ideally air-conditioned space, drinking liquids, loosening clothes and applying wet cloths are some of the recommended steps that can help keep heat exhaustion from progressing to the most dangerous form of heat-related illness, heat stroke.

Heat stroke is a medical emergency. At this point, the body can no longer maintain a stable core temperature. A body with heat stroke can reach 106 degrees Fahrenheit or higher rapidly, and that heat can quickly damage the brain, heart and kidneys.

Typically, someone suffering heat stroke has exhausted their reserves of sweat and salt to stay cool, so sweating eventually stops during heat stroke. Their cognitive ability fails, and they cannot remove themselves from danger. Heat stroke can cause seizures or put someone into a coma as their core temperature rises. If the condition is not treated immediately, and the core temperature continues to rise, heat stroke becomes fatal.

Because heat exhaustion can lead to heat stroke, addressing heat-related illnesses before they progress is vital.

How to tell when the heat is too high

Heat risk isn’t just about temperature – humidity also increases the risk of heat-related illnesses because it affects how well sweating will cool the human body when it gets hot.

Instead of just looking at temperature when planning outdoor activities, check the heat index, which accounts for heat illness risk associated with temperature and relative humidity.

It doesn’t take very high temperatures or very high humidity for the heat index to enter dangerous territory.

However, the heat index is still a conservative measure of the impact of heat on humans, particularly for outdoor workers and athletes at summer practices. This is because temperature measurements used in weather forecasting are taken in the shade and are not exposed to direct sunlight. If someone is outside and exposed to the direct sun, the actual heat index can be as much as 15 F higher than the heat index chart indicates.

A more sophisticated measurement of heat effects on human health is what’s known as the wet-bulb globe temperature, which takes into account other variables, such as wind speed and cloud cover. Neither takes into account a person’s physical exertion, which also raises their body temperature, whether working at a construction site or playing soccer.

Tips for staying safe in a heat wave

How can you stay cool when heat waves set in? The answer depends in part on where you are, but the main points are the same:

• Avoid strenuous outdoor activities in high temperatures if possible. If you start to feel symptoms of heat-related illnesses, drink fluids that will hydrate you. Find shade, rest, and use cool, damp cloths to lower your body temperature. If you see signs of heat stroke in someone else, call for medical help.

• Be careful with fans. Fans can be useful if the temperature isn’t too high because they wick sweat away from the body and induce evaporative cooling. But at very high temperatures, they can accelerate heat buildup in the body and lead to dangerous conditions. If indoor temperatures reaches 95 degrees or higher, using fans can actually be dangerous and raise the risk of heat-related illnesses.

• Find a cooling center, library or community center where you can get inside and rest in an air-conditioned space in the hottest hours. In places such as Phoenix, where high temperatures are a regular hazard, cooling centers are typically opened in summer. Northern cities are also opening cooling centers as heat waves occur there more frequently than they did in the past. Urban areas with a lot of pavement and buildings – known as heat islands – can have temperatures well above the city’s average.

• Hydrate, hydrate, hydrate! Drink plenty of fluids, and don’t forget about the importance of electrolytes. Heat-related dehydration can occur when people sweat excessively, losing water and necessary salts from the body. Some sports drinks or rehydration fluids restore electrolytes and hydration levels.

Older adults and people with disabilities often face higher risks from heat waves, particularly if they can’t easily move to a cooler environment. Communities and neighbors can help protect vulnerable populations by providing cooling centers and bottled water and making regular wellness checks during high heat.

Summer can be a season of fun. Just remember the risks, keep an eye on your friends and neighbors when temperatures rise, and plan ahead so you can beat the heat.

Brian Bossak, Professor of Public Health, College of Charleston

This article is republished from The Conversation under a Creative Commons license. Read the original article.