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Researchers search for more precise ways to Measure Pain Better Health
By M ark Johnson
The Washington Post
Madison Evans was 16 when she first felt the sharp pain in her lower pelvis, pain that radiated through her back and grew so severe that some days she could not get out of bed. Pain relievers “couldn’t touch it,” she said. “Sports, social events, whatever was on the calendar had to be cleared.”
The pediatricians Evans visited during her adolescence in Severna Park, Maryland, never asked her to rate the pain. Instead they told her, “The cramps are bad when you’re young” and, “You’ll grow out of it,” then prescribed the ineffective pills.
She did not grow out of the pain; it continued for almost 15 years. Relief only came at age 30 when a doctor listened to her descriptions of the pain and diagnosed endometriosis, a chronic condition that affects 1 in 10 women of childbearing age.
Measuring pain, one of the most fundamental tasks in medicine, remains one of the least precise, a shortcoming that helped fuel the nation’s opioid crisis. In an era of genomic medicine and artificial intelligence, doctors still ask patients to rate their pain from 0 to 10 or, in the case of very young children, with cartoon faces, ranging from smiley to frowny.
Studies have shown that these efforts are undermined by biases that have led the medical community to consistently underestimate the pain of women and minorities, especially Black Americans.
But researchers are now on a quest to find objective biological indicators of pain that will enable doctors to quantify it as they do heart rate and
blood pressure. The wave of research into these indicators, known as biomarkers, carries implications for the nearly 1 in 4 Americans who live with chronic pain. It may also speak for infants and others who are unable to tell doctors what they feel.
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measure pain using these markers would improve the accuracy of diagnoses and help determine how effective medications are in easing their patients’ suffering.
An accurate objective pain measure could also wind up saving the health-care system
Finkel said. “The current standard of care is that we ask the patient a bunch of questions; laboratory data is drawn. They get back to you next week. Then that next visit, which is the following month, based on what we saw in the labs, then we’ll escalate
Finding an objective measure of pain could also topple the barrier of doubt that sometimes stands between doctors and their patients, a problem Gissel Moralescasco ran into when she was 8. A doctor had asked her to rate the pain that spread from her
One problem with using pain scales alone is that they’re imprecise and vulnerable to manipulation. Craving medication, some patients overrate their pain; others, fearing they’ll be viewed as overly sensitive, downgrade their pain.
Scientists hope to identify biomarkers among the proteins, hormones and metabolites that have been linked to pain. One researcher has been developing a way to measure the pain sensations transmitted by nerve fibers in the body.
Doctors said the ability to
money, said Julia Finkel, an anesthesiologist at Children’s National Hospital in Washington, who is hoping to develop the first device to determine both the type and intensity of pain.
“You get it right the first time instead of this empirical, trial-and-error approach,”
the dose, or decrease the dose or change the drug.”
In 2010, the National Academy of Sciences put the annual cost of chronic pain at between $560 billion and $635 billion - up to $300 billion of that in direct health-care costs and up to $110 billion in missed time at work.
stomach through her entire body on a scale of 0 to 10, with 10 being the most severe.
“Ten,” she said, without hesitation.
“Are you sure?” the doctor asked. “Ten is really bad.”
Two months later, a different doctor spent almost a day examining Moralescasco and
running through tests before diagnosing the D.C. resident with lupus.
“Wow,” the doctor told her. “Now I understand.”
Although pain is sometimes called the fifth vital sign after temperature, pulse, respiration and blood pressure, its complexity often goes unappreciated.
“When patients are told that the pain is all in their head, the implication is that it’s imagined, but the irony is that [is] sort of right,” said Adam Kepecs, a professor of neuroscience and psychiatry at Washington University in St. Louis.
“The pain only exists in your brain. It’s neural activity, which is why it’s invisible and uniquely personal. But it’s still real.”
Kepecs and a colleague have a $3.4 million federal grant to develop a blood test that can measure pain in women who, like Evans, have endometriosis, which stems from the growth of tissue similar to the lining of the uterus but in the pelvic area outside the uterus.
“By comparing blood samples from the same individual at different times, when they experience high pain versus no pain, we can identify molecules specifically linked to pain,” Kepecs said.
At Children’s National Hospital, Finkel has an $8 million grant from the same federal program funding Kepecs’s project. In about two months, she plans to start clinical trials of the tool she has dubbed the Nociometer. The name is a nod to the term nociception, the detection of pain.
The Nociometer stimulates the patient’s three main
sory and
Left: Julia Finkel, M.D., 62, pediatric anesthesiologist and director of Pain Medicine Research at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital. Finkel is also the founder of AlgometRx, a medical device startup spun out of Children’s National in 2015. Right: A model of The AlgometRx Nociometer®, a pain assessment device that uses pupil dilation analysis to characterize pain type and intensity. (PHOTOS COURTESY OF CANDACE DANE CHAMBERS / THE WASHINGTON POST)
How
Metabolism is often discussed but perhaps not fully understood.
Does exercise boost metabolism?
Tips to overcome seasonal
metabolism allergies
The Cleveland Clinic says a person’s metabolism encompasses all of the processes within cells that keep the body functioning as it should. Metabolism provides the body with constant energy so it can perform essential tasks like breathing and digestion. There are many myths surrounding the metabolic process. The following are some things to know about metabolism and whether it is possible to utilize it to spur weight loss.
What is a fast metabolism or a slow metabolism?
A person’s basal metabolic rate (BMR) may be fast, slow or somewhere in between. Someone with a fast BMR will burn a lot of calories, even while at rest. Those with a slow BMR need fewer calories to keep it going. Genetics, medication use, illness, and activity level may affect BMR.
The answer to this question is yes and no. According to MedlinePlus, it is true that a person burns more calories when they exercise, but that increased calorie burn only lasts as long as the workout and maybe an hour or so afterwards. Once a person stops moving, his or her metabolism goes back to its resting rate. Therefore, eating a ton of calories after a workout thinking that a red-hot metabolism will burn through them for the rest of the day could be setting a person up for weight gain. The same can be said for mistakenly thinking adding muscle will boost metabolism. Muscle burns more calories than fat and that boost does last a bit longer than the workout itself. However, most people only gain a few pounds of muscle in the exercises they do. It’s not a big enough difference to affect metabolism dramatically. One may have to be a body builder to see a BMR boost associated with strength training. When muscles are not in active use, they burn very few calories.
What has the biggest impact on metabolism?
Metabolism is largely influenced by genetics, according to Harvard Health Publishing. Therefore, diet and exercise can be beneficial, but ultimately a person’s genes dictate BMR.
Also, most of the time the activities of keeping the brain, heart, kidneys, and lungs working account for most of a person’s metabolic function.
What is diet-induced thermogenesis?
Many people think that restrictive diets that are light on calories are good for losing weight, but that can sometimes backfire by slowing down a person’s BMR. Harvard Health says diet-induced thermogenesis (DIT), or the effect of eating certain metabolism-boosting foods, may increase resting metabolic rate. Foods and beverages that may impact DIT include lean protein, unrefined carbohydrates, caffeine, and green tea. DIT tends to be higher in the morning, so eating larger meals earlier in the day may help burn more calories. How does sleep affect metabolism?
While the jury is still out on whether or not lack of sleep can lower BMR, a 2019 study published in the Journal of Lipid Research found that a lack of sleep for four nights or longer may slightly decrease how the body metabolizes fat. Also, those who don’t get enough sleep often feel hungry and may overeat as a result. This isn’t a direct metabolic cause, but one to consider nonetheless.
Metabolism is a complex process that is affected by many things, none greater than genetics. A person may be able to realize moderate gains in boosting metabolic rate but there is no magic pill to increase metabolism.
Spring and summer are typically welcomed with open arms. Warm weather, blooming flowers and trees full of leaves are a welcome sight for many, but seasonal allergy sufferers may find the transition from winter to spring a little more challenging.
The Center for Health Statistics found that just under 26 percent of adults and roughly 19 percent of children have a seasonal allergy. Treatments for seasonal allergies can be effective, and many people find overthe-counter medications are enough to alleviate their symptoms. But even people who take OTC medications daily may have days when seasonal allergies cause considerable discomfort. In such situations, allergy sufferers can consider these strategies.
Identify your triggers
The American College of Allergy, Asthma, & Immunology notes that pollen is the most common outside allergy trigger. Trees and
grasses typically pollinate in spring and summer, which is why these seasons can be especially challenging for people with seasonal allergies. Dustmites and pets might trigger allergies indoors, but these can appear throughout the year. A visit to an allergist can determine what exactly triggers seasonal allergies. For example, certain types of grasses and trees might be triggers for some but not others. Identifying triggers is an effective first step because it can compel people to avoid the things that cause allergic reactions.
Stay indoors on dry, windy days
The Mayo Clinic advises seasonal allergy sufferers to stay indoors on dry, windy days, when pollen can be nearly impossible to avoid.
Take advantage of a good rain
The Mayo Clinic advises that the best time for seasonal allergy sufferers to be outside is after a good rain. Rain helps to clear pollen from the air, so post-rain conditions can be ideal for people with seasonal allergies.
Change your clothes and wash up upon coming inside
The ACAAI recommends changing clothes, washing them and taking a shower upon coming inside during allergy season. Washing clothes and taking a shower reduces the likelihood that you’ll spread pollen around the interior of your home, where it can attach to furniture and trigger allergic reactions.
Monitor the pollen count
As noted, pollen is a seasonal allergy trigger, so allergy sufferers are urged to monitor the pollen count via a website such as Pollen.com, where visitors can type in their ZIP code and get an up-to-date allergy report. On days when the pollen count is high, stay indoors and keep windows closed so the pollen does not get inside. The Mayo Clinic notes that pollen counts tend to be highest in morning, so it’s best to avoid being outside during this time of day. Seasonal allergies can make spring and summer more challenging. A few simple strategies can help people control their seasonal allergies even on days when pollen counts are particularly high.
Did you know?
The U.S. Department of Health and Human Services reports that pollen season is getting longer and increasing in intensity. Shifts in precipitation patterns, more frost-free days, warmer seasonal air temperatures, and greater amounts of carbon dioxide in the atmosphere, each of which are side effects of climate change, have led to higher concentrations of pollen in the air and longer pollen seasons. Data from the USA National Phenology Network, which provides data on the timing of seasonal events in plants and animals to ensure the well-being of humans, ecosystems and natural resources, indicates total pollen counts increased by as much as 21 percent between 1990 and 2018. Such data may come as no surprise to people with asthma and seasonal allergies who have noticed the side effects of such conditions tend to start earlier than in the past and extend for longer periods of time than in previous years.
Common health issues affecting
women
Preventive health care is a multifaceted approach that aims to keep people healthy and reduce their risk for various diseases and conditions.
Health education is one facet of preventive health care that can be easily overlooked, particularly by busy adults juggling an assortment of responsibilities.
Health education includes recognition of various conditions that pose a threat to individuals. Women can do their best to learn about issues that commonly affect them with a goal of taking steps to reduce their risk for various diseases and conditions. Northwestern Medicine¨ reports that the following are some of the most common health issues affecting women today.
Heart disease:
Stroke:
Both men and women might be shocked to learn that more women die from stroke than men. Difficulty with speech and numbness of the arms and legs are prominent symptoms of stroke.
Diabetes:
Women with diabetes have a four times greater risk for heart disease than women who do not have diabetes. Making an effort to maintain a healthy weight and committing to routine exercise can lower risk for type 2 diabetes. Quitting smoking also lowers a woman’s risk for diabetes.
Urinary tract infections:
Breast cancer:
Breast cancer is the most common form of the disease in women. Women in the United States have a 13 percent chance of developing breast cancer, and that risk may be even higher for women living outside the U.S. Agebased screening and healthy lifestyle choices like exercising and avoiding tobacco can help women in the fight against breast cancer.
Alzheimer’s disease:
Understanding the Menopause Transition
The human body is capable of various amazing feats, but many will attest that the ability of women to nurture and grow what will become another person is the body’s most impressive characteristic.
Healthline states a woman can get pregnant and bear children from puberty, when they start getting their menstrual periods, to menopause. The average woman’s reproductive years are between ages 12 and 51. While puberty and pregnancy are topics widely discussed in a woman’s life, the same may not be said for menopause. What is menopause?
The World Health Organization characterizes menopause as the end of a woman’s reproductive years. After true menopause, a woman cannot become pregnant naturally. Menopause is marked by the end of a monthly menstrual cycle often referred to as a ‘period.’ Natural menopause is deemed to have occurred after 12 consecutive months without menstruation. Menopause can occur for other reasons, such as if the reproductive organs are damaged due to illness or removed for the treatment of a certain condition. This is called induced menopause. What happens during menopause?
During menopause, the ovaries stop producing reproductive hormones and stop releasing eggs for fertilization, says the Cleveland Clinic.
What is perimenopause?
Some people incorrectly describe the years leading up to
the last menstrual period as menopause. However, menopause only occurs after the last period has occurred. It is a finite date. The menopausal transition before that takes place is actually called perimenopuase. It is a period of time that most often begins between ages 45 and 55. The National Institute on Aging says perimenopause traditionally lasts seven years, but it can go on for as long as 14 years. The duration may depend on lifestyle factors, race and ethnicity. During perimenopause, production of estrogen and progesterone made in the ovaries varies greatly. That can mean menstruation can be heavy at times or light. It may occur once a month or even multiple times per month. The menopausal transition affects each woman differently. It is a good idea for women to use a menstruation tracker and remain aware of symptoms to discuss with the gynecologist. What is postmenopause?
Postmenopause is the time after menopause has happened. Women will remain in postmenopause for the rest of their lives. While many symptoms ease up in postmenopause, there still may
be mild symptoms attributed to the low levels of reproductive hormones. What are common symptoms of the transition?menopause
As one transitions from childbearing years into postmenopause, certain symptoms can occur.
• Irregular periods
• Hot flashes/night sweats
• Vaginal dryness
• Urinary urgency
• Difficulty sleeping
• Emotional changes
• Dry skin, eyes or mouth
• Worsening premenstrual syndrome symptoms
• Breast tenderness
• Headaches
• Racing heart
• Joint and muscle aches
• Weight gain
• Trouble concentrating
• Changes in libido
Women are urged to discuss their symptoms and concerns about menopause with a health care professional. Various treatments can alleviate symptoms and make the transition more comfortable.
It’s common to view heart disease as a killer of men, but women should know it’s the No. 1 cause of death for women. Menopause does not cause heart disease, but certain risk factors for heart disease, including high blood pressure, elevated cholesterol levels and lower levels of estrogen, are more common in post-menopausal women.
People assigned female at birth have shorter urethra than those assigned male at birth. A shorter urethra means bacteria does not have to travel as far to reach the bladder, and UTIs are caused by germs that enter the urethra and multiply. Frequent urination, painful urination and cloudy urine are common symptoms of UTIs.
More than two-thirds of the six million Americans living with Alzheimer’s disease are women. Women historically have lived longer than men, but researchers are exploring if that is the only reason for the disparity between rates of Alzheimer’s in women compared to men. A healthy diet and routine physical activity are some of the ways to promote brain health and potentially reduce Alzheimer’s risk.
Recognition of risk for specific diseases can be a vital component of preventive health care that encourages women to take steps that can decrease the chances they develop various conditions.
What to know about Lupus
Estimates from the Lupus Foundation of America indicate roughly five million people across the globe have a form of lupus. Though that figure suggests a person’s chances of developing lupus are slim, it’s still worth anyone’s time to gain a basic understanding of the disease.
What is lupus?
The Lupus Research Alliance reports lupus is a serious autoimmune disease that prompts the immune system to attack healthy cells by mistake. Lupus is a chronic disease that requires long-term treatment. The LRA notes that symptoms vary among individuals with lupus, which can make the disease difficult to detect.
Types of lupus
Lupus Canada notes that there are four different types of lupus.
Systemic lupus erythematosus (SLE)
SLE is a chronic illness, but Lupus Canada notes that most people diagnosed with it are not continuously sick for the rest of their lives. The LRA reports SLE affects many parts of the body. If left untreated, the inflammation resulting from SLE can cause organ damage and compromise organ function.
Cutaneous lupus
Cutaneous lupus causes a rash or lesion on the skin, typically after skin is exposed to sunlight. Lupus Canada
notes cutaneous lupus is not life-threatening and does not affect internal parts of the body. However, cutaneous lupus may sometimes occur along with SLE, so individuals may experience skin rashes in addition to symptoms associated with SLE.
Drug-induced lupus
Some people develop lupus due to an overreaction to certain medications. In such instances, the disease is characterized as drug-induced lupus and typically goes away once a person stops taking the medication that triggered the response.
Neonatal lupus
The LRA notes that autoantiobodies are immune proteins that mistakenly
target the body’s own tissues and organs when a person has an autoimmune disease, such as lupus. Neonatal lupus occurs when an infant acquires autoantibodies from a mother with SLE. Issues associated with neonatal lupus, including problems that affect the skin, liver and blood, typically resolve within six months. However, congenital heart block associated with neonatal lupus requires a pacemaker. Symptoms of lupus Symptoms of lupus vary so widely that the LRA characterizes it as “the disease with 1,000 faces.” However, some symptoms are more common than others. The LRA notes the most common symptoms of lupus include:
Fatigue - As many as 90 percent of lupus patients identify fatigue as a primary symptom of their condition. However, the LRA notes that scientists remain uncertain if the fatigue lupus patients feel is a byproduct of the disease or the treatments used to manage it.
Butterfly rash - Also known as a malar rash, the rash that appears across the cheeks and the bridge of the nose in the shape of a butterfly is experienced by roughly half of all people with lupus. The rash is red and can last from days to weeks, and some people experience pain or itchiness as well.
Arthritis - The LRA reports that up to 90 percent of people with lupus will have arthritis.
Unexplained fever - Most people with SLE experience unexplained fevers (body temperatures over 100 F). Are some people more vulnerable to lupus?
Lupus Canada reports women of childbearing age are most often affected by lupus. Though men, children and the elderly are not immune to lupus, Lupus Canada indicates the disease is eight to 13 times more common in women between the ages of 15 and 45 than in men.
Lupus can pose a notable threat to those diagnosed with the disease.
- found in skin, muscles, joints and some organs - without actually causing pain. Instead, the device sends a tiny electrical current through a probe, usually attached to the patient’s finger or toe. The three fibers each transmit a different kind of sensation: temperature and slow-burning pain; sharp, localized pain; and touch and pressure.
Using a handheld instrument, the doctor then examines the dilation of the patient’s pupil in response to the electrical current. The pupil is connected to the pain processing centers of the brain that receive information from the three nerve fiber types. Finkel’s Nociometer measures and compares the relative sensitivity of each type and uses the information to determine the kind of pain and its intensity.
The clinical trials will test the device’s accuracy in measuring pain associated with different conditions, includ-
ing pediatric acute postoperative pain, lupus (an example of inflammatory pain) and carpal tunnel syndrome (an example of neuropathic pain, which arises from damage or dysfunction of the nervous system, rather than from damage to tissue).
Another study will evaluate people without pain, though “they’re hard to find,” Finkel said. The Nociometer would not replace the self-reported pain scales that doctors use, but rather add clarity.
“Well, you said ‘I’m in pain.’ I don’t doubt that,” Finkel explained. “In order to be most effective, I need to know why; what are the underpinnings of why you feel this way. Different components impact one’s perception of pain. Depression can exacerbate it. Happiness can mitigate it.”
One problem with using pain scales alone is that they’re imprecise and vulnerable to manipulation. Craving medication, some patients overrate their pain; others, fearing they’ll be viewed as overly sensitive, downgrade
their pain.
“You don’t want to leave people in terrible pain, but the problem we got into is that that seemed to translate into large amounts of opioids being prescribed,” said David Clark, a professor of anesthesiology, perioperative and pain medicine at Stanford Medicine, an academic medical center that is part of the university.
Clark said doctors try to go beyond the self-reported scales by asking specific questions: How does the pain interfere with the things you want to do? Can you work? Can you take care of your kids? Is the pain interfering with sleep?
Still, health-care professionals struggle with their biases, and with the significant challenge of determining pain in newborns and young children who cannot communicate.
“There is a huge need, really, for objective biomarkers to assess pain in these vulnerable populations,” said Neha Santucci, director of the chronic abdominal pain program at Cincinnati Children’s
hospital.
Since infants cannot talk, Santucci said, “we go by more of their behavior. Crying is a sign of being in discomfort, but babies cry. Crying is their primary language. A baby crying does not necessarily mean pain. They might be crying because they’re hungry. They may be crying because they need a diaper change.”
Kevin Jackson, Finkel’s partner in the company AlgometRx, which will produce the Nociometer, said they hope the device will receive approvals and be ready for clinical use within about five years. Although the cost has not been decided, Jackson said it will probably be between $10,000 and $15,000.
“We do envision it being a ubiquitous tool,” he said.
The projects involving Finkel and Kepecs are among four aimed at developing ways to measure pain, all funded with grants from the Department of Health and Human Services’ Advanced Research Projects Agency for Health. Another recipient, Tufts University biomedical en-
gineering professor Sameer Sonkusale, is using a $3 million grant to develop a patch containing microneedles that is placed against the skin. The microneedles would take samples of interstitial fluid, the watery substance found between cells and tissues in the body.
Doctors would peel the patch off after 35 to 40 minutes and insert it into a reader that would search for molecules such as hormones, metabolites and cytokines (small proteins important in cell signaling), Sonkusale said. The patches, he said, should be ready for human testing within six months.
“The whole project rests on the premise that there’s no one biomarker of pain,” he said. “We are looking for a panel [of different biomarkers].”
The fourth project is led by Wei Gao, a professor of medical engineering at the California Institute of Technology, who received a $3 million grant to develop a “wearable” pain tool that would measure pain through proteins,
hormones and metabolites found in sweat. It might be a ring or a device worn around the wrist like the Fitbit, which tracks a person’s fitness.
“A lot of biomarkers associated with pain can be identified in blood,” he said. “But taking a blood draw at home would not be practical.”
That’s why, Gao said, “we are looking at what’s in the sweat.”
The as-yet-unnamed device can actually induce sweat, even while the wearer is sleeping. Gao said it would consist of a disposable patch costing less than $1 that would collect the sweat and a reusable reader that costs between $10 and $20.
Evans, the woman with endometriosis, who now lives in St. Louis, said the ability to measure pain through methods like the blood test being developed for her condition will have profound implications for patients.
“I think if the blood test had existed 15 years ago,” she said, “I would have essentially gotten those 15 years of my life back.”
Left: Research into pain biomarkers and artificial intelligence has been progressing as scientists and doctors seek a way to quantify pain. Right: (L-R) Researcher Kevin Jackson, 31, and Julia Finkel, M.D., 62, demonstrating how to use the AlgometRx Nociometer®, a pain assessment device that uses pupil dilation analysis to characterize pain type and intensity. Jackson and Finkel are the COO and founder of the private company, AlgometRx, a medical device startup that was spun out of Children’s National Hospital in 2015. (PHOTO BY CANDACE DANE CHAMBERS FOR THE WASHINGTON POST)