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    The science of pain: What is it and why is it so hard to measure?

    Chronic pain is one of humanity’s most common ailments, but its biological mechanisms remain a mystery. While researchers seek answers, doctors focus on how pain affects a patient’s life.

    Medical pain diagnosis meter level scale with emoji symbols.

    During just about any doctor’s appointment with a patient who complains of pain, there comes an awkward moment when the doctor asks a seemingly straightforward question: “How badly does it hurt?”

    The patient struggles to answer. They worry about minimizing the pain, which could mean it doesn’t get sufficiently addressed, but also about overstating the pain, which could make them come off as exaggerating.

    “Pain is a very personal experience and hard for a lot of people to put into words,” says Erin Krebs, MD, MPH, chief of general internal medicine at the Minneapolis VA Health Care System and a professor at the University of Minnesota. “You have to interpret it.”

    The doctor tries to help: On a scale of 1 to 10, does the level of pain feel like a 2 (mild), a 6 (severe), a 10 (worst possible)? Look at this series of emoji faces: When it hurts, do you feel like the face that’s expressionless? Frowning? Crying?

    Many doctors and patients find such pain measuring tools okay for a superficial start but ultimately inadequate for assessing chronic pain to a degree that informs effective treatment.

    “That measure alone is not sufficient to really understand what the patient is experiencing,” says Christine Goertz, DC, PhD, professor of musculoskeletal research at the Duke Clinical Research Institute and director of system development and coordination for spine health in the Department of Orthopaedic Surgery at Duke University in North Carolina.

    Yet doctors need to get the picture somehow: Twenty-one percent of U.S. adults (nearly 52 million people) report feeling chronic pain, according to survey results published in April by the Centers for Disease Control and Prevention. That report notes that chronic pain (generally defined as pain lasting more than three months) is “one of the most common reasons that adults seek medical care,” and links it to anxiety, depression, opioid dependence, restrictions in mobility and daily activities, and reduced quality of life.

    A core challenge in assessing chronic pain is that pain is not a stand-alone ailment; it is the body’s response to other developments, including injury, infection, and disease. It’s a signal that something’s wrong.

    “We think about pain as being caused by one thing, but often it’s not that simple,” Goertz says. “There are many things we still don’t know about pain.”

    Part of the mystery is that pain is more than biological — psychological, emotional, and social conditions influence how each person experiences it at any given time.

    “I view pain as a decision-making process,” says Lauren Atlas, PhD, chief of the Section on Affective Neuroscience and Pain in the National Institutes of Health’s Intramural Research Program. This subconscious decision is influenced by many factors, she says, including stimuli from physical harm (such as a slipped vertebra); interoception, which is how a person senses what is happening in their body overall (such as hunger and warmth); and one’s emotional and psychological states at any given time.

    “If I’m in a very anxious state, or I’m feeling relaxed, I might be paying different attention to my pain, which might make it feel very different,” Atlas notes.

    Given that pain is a universal human experience, researchers continue experimenting to determine what pain is — including how the body experiences and communicates about it. Meantime, doctors continue to focus more on how pain affects a patient’s life.

    Tracing the biology of pain

    After coping with lower back pain on and off for 20 years, a woman walked into her doctor’s office in Iowa one day saying that the pain had suddenly gotten so severe that she had trouble sleeping, getting dressed, and walking her dog. On a scale of one to 10, she rated her pain an 8.

    Why the drastic change? Pinpointing the source of back pain is particularly difficult because so many factors — such as the condition of bones, muscles, ligaments, and nerves — are at play, doctors say. The woman said the pain got noticeably worse, and spread upward, while she was gardening a couple of weeks earlier. Gardeners know well how all that bending and twisting can put unusual stress on someone’s back.

    Physical exams showed restricted joint movement along with tenderness along the woman’s upper back muscles, but tests of orthopedic conditions, nerve signals, and motor strength came back with normal results. In short, there was no clear indication of a severe change that would spike her pain to unprecedented levels.

    The case, related by Goertz (who knows the case but did not treat the patient), illustrates common challenges in exploring the biological mysteries of a patient’s pain.

    “Often there’s no physical evidence of pain,” says Robert Gereau, PhD, director of the Washington University Pain Center and vice chair for research in the Department of Anesthesiology at Washington University School of Medicine in Saint Louis. “But it’s not the case that there’s nothing wrong just because you can’t see what’s wrong.”

    Even when pain does stem from identified tissue damage, Gereau says, the severity or duration of the damage might not align with the severity or duration of the pain. A broken bone or sprained joint sometimes stops hurting long before the injury appears to have healed; other times, the pain continues long after.

    That frustrates doctors and patients alike. “What patients want to know,” notes Krebs, “is, ‘What’s going on in there?’”

    Researchers are making progress toward finding out, often by using brain imaging to observe changes in how neural signals trigger the feeling of pain.

    The Gereau Lab at Washington University School of Medicine studies chronic pain as a disease stemming from modifications in neural circuits that regulate painful sensations. The plasticity of those circuits causes them to adapt to painful events, creating patterns of pain signals that repeat as a sort of memorized response, Gereau says.

    “The changes [that deliver pain signals] are in your nervous system,” he says. “That’s not something you can see, but it doesn’t mean that it’s not real. It’s just very frustrating for patients and a challenge for physicians.”

    Researchers are looking for ways to disrupt the pain signal pattern and “push those circuits back to function normally,” Gereau says.

    Another line of research explores whether someone’s expectations about pain affect how the body responds to actual pain. For example, when study participants receive a placebo that they expect to reduce the pain from a harmful stimulation (such as heat), they often report feeling less pain than people in control groups, as explained in a recent meta-analysis of 20 such studies. At the same time, brain imaging shows “widespread reductions in pain-related activity” in areas of the brain related to pain, emotional regulation, and decision-making.

    Atlas, who has studied the impact of placebos as well as perceived physician competence on reports of pain, says the findings suggest that patient expectations about whether they are going to experience pain sometimes affect the actual biological experience. Still to be determined is precisely how and to what extent.

    Impact on life

    For front-line physicians, the increasingly important measure about a patient’s pain is not how much it hurts but how much it interferes with what matters to the patient.

    “The most important thing is how is this pain affecting your life or changing your activities,” Krebs says. “It could be severe pain but it’s not stopping you from doing anything. That’s a very different situation than if you’ve had to give up your work or your hobbies. Or you’re so miserable because of this pain that you can’t focus on anything.”

    This impact, called “functional interference,” became the focus of the physician’s pain assessment for the Iowa woman with the suddenly severe back pain. Aside from the interference with basic activities of daily living — like sleeping and dressing — she told her doctor that she wanted to be able to travel to visit her grandchildren.

    “What mattered is that the pain limited her ability to do things that were important to her,” Goertz observes. At her doctor’s suggestion, the woman made an appointment with a chiropractor.

    Several pain measuring tools go beyond the basic pain-level scales to ask about how the pain affects quality-of-life activities and states of mind. The Pain, Enjoyment of Life and General Activity (PEG) scale is a three-question initial assessment that asks people to rate their level of pain, then how the pain interferes with their enjoyment of life and with general activities. For deeper dives that take more time, there are longer and more detailed questionnaires. PROMIS (Patient-Reported Outcomes Measurement Information System) asks patients to score the degree to which pain interferes with work, various household chores, and social activities, and to rate their level of anxiety and fear. The Roland-Morris Disability Questionnaire asks patients with lower back pain to respond to statements such as “I have to hold on to something to get out of an easy chair” and “I stay at home most of the time because of my back.”

    “It’s the effect on your life that will give me a sense for where to focus my energy,” says Krebs, who developed the PEG scale.

    The use of these tools while researchers are finding biomarkers for pain raises the question: Can’t doctors also use technology that measures brain signals to provide an objective measure of a person’s pain? Pain experts say the brain imaging equipment is too costly and the process too time-consuming to be of routine use in physicians’ offices. Besides, the benefits might not be so great.

    “There is nothing I am aware of that would reliably predict a patient’s pain experience” based on biomarkers, Goertz says. Regardless of the readings from a machine, the actual pain “may feel completely different to you than it does to me.”

    Atlas worries that such readings might skew a doctor’s assessment of a patient’s pain. She envisions a patient saying, “I’m feeling pain,” but a machine that scans for biomarkers finds no evidence, leading the doctor to say, “No, you’re not.”

    “You don’t want to invalidate anybody’s pain,” Atlas says.

    That leaves doctors with various ways to work with patients to assess pain on several levels, from the physical feeling to the emotional context to the impact on their lives.

    “If you are a physician,” Goertz says, “you have a moral obligation to understand pain and manage it well.”