Over the past few years, medical science has been making new discoveries in addressing the problem of pain
By Wendy Haaf
Anyone who’s ever sprained an ankle or pulled a muscle knows what it’s like to wake up trying to gauge whether the pain might have improved overnight.
For an estimated one in five Canadians—one in three of those over 65—the number on a zero-to-10 pain scale may be higher or lower on a given day, but it’s never zero; they live with chronic pain.
Defined as pain that lasts longer than three months, chronic pain is recognized as a diagnosis in its own right by the World Health Organization. It can cause ripples in every area of life, affecting everything from relationships and sleep quality to susceptibility to depression and anxiety. However, researchers around the world are constantly learning more about the different factors that contribute to various types of chronic pain, testing strategies for alleviating the suffering that often accompanies it, and uncovering techniques that could prevent it from arising in the first place. Here are just a few of the promising developments.
Reinforcing the Role of Lifestyle
In many kinds of chronic pain, there’s no detectable damage that can explain why the person is in pain. It’s a bit like tinnitus—the ringing, buzzing, or other noises that a person hears inside their own head: outsiders and even medical professionals can’t sense it, but it exists nevertheless. This type of chronic pain seems to be linked to a sort of rewiring of the brain, and as with a defective car alarm that goes off for no reason, there’s no way to switch it off. Even in chronic conditions in which pain is related to changes such as inflammation, what’s going on in your brain affects pain; since all nerve signals are routed through it, the brain can amplify or dampen the sensation.
Consequently, pain is tightly entwined with mood and sleep. “They’re all connected,” stresses Dr. Andrea Furlan, a senior scientist and pain physician at the University Health Network’s Toronto Rehabilitation Institute. (She has her own YouTube channel featuring hundreds of helpful videos on various aspects of pain management.)
According to Furlan, the jury is already in on how effective a range of lifestyle changes are for helping people with chronic pain cope more effectively and feel better. “We don’t even need to do more studies,” she says. Compared to medications, “cognitive behavioural therapy [CBT] for sleep and counselling or talking to someone for your mood will give you much better results,” she says. “I tell my patients you don’t have to do CBT counselling for the rest of your life—just do a few sessions and learn the skills.”
Furlan stresses that a healthy diet and regular exercise also play important roles in pain management due to their effects on the brain. “We have an inner pharmacy in our brain stem, which is where you produce endorphins— which are powerful painkillers—and where dopamine and serotonin are released,” she explains. The latter two substances are chemical messengers that are involved in regulating a host of functions, including mood, sleep, digestion, and motivation. And to make adequate supplies of serotonin and dopamine, your body needs specific nutrients. For example, to produce serotonin, the body needs an amino acid you can obtain only from food: L-tryptophan. “If you don’t eat that amino acid, you’re not producing enough serotonin to fight depression and pain,” Furlan explains. Good sources of L-tryptophan include poultry, eggs, fish, cheese, milk, and nuts.
Similarly, during exercise, your body releases a torrent of different chemicals, including endorphins, which, in addition to easing pain, buffer stress and lift mood. Exercise also triggers a flood of a substance called brain-derived growth factor (BDNF). BDNF is crucial for the survival, development, and growth of nerve cells and for a trait known as brain plasticity—the organ’s ability to change and adapt by forging new neural connections and pathways.
Furlan offers this snapshot of what BDNF does: “If you use muscles you haven’t used in a long time, you get delayed-onset muscle soreness. When I graduated from medical school, we were taught that this soreness was due to the release of lactic acid. It’s not. If you don’t use a muscle, the nerve endings connected to that muscle kind of shrink because they’re not needed.” When you use the muscle, the nerve endings start growing, and that regrowth—which BDNF makes possible—causes the soreness. Furlan advises her patients to incorporate both aerobic activity and strength training into their lives. “Gain muscle,” she says. “That’s the message, because it’s good for not only your bones and your balance but also your brain and will help you live longer and better.”
Access to health professionals with different areas of expertise, including psychological therapies, occupational therapy, and physiotherapy, is likely a major contributor to the following fact. “People who end up in multidisciplinary pain clinics typically do very well,” says David A. Seminowicz, a professor and Wolfe-Western Fellow at Western University’s Schulich School of Medicine & Dentistry in London, Ont., and co-director of the kNOw-Pain research group at Western’s Robarts Research Institute. Unfortunately, these clinics, which are concentrated in urban centres, are available to only a fraction of a percentage of Canadians, he adds.
Another reason for the success of interdisciplinary clinics is their ability to tailor the treatment plan to the patient. “They usually assess a person and decide what type of intervention is going to be the best, which takes time and multiple visits,” Seminowicz says. “Is stress a factor? Can we do something to decrease the stress? Is it a muscle problem that we can get our physical therapist and massage therapist to address? That’s the kind of personalized approach that it typically takes.”
New Evidence for Non-Drug Therapies
“One direction research has been headed in for several years is looking at individualized treatments, the whole person, and combination therapies,” Seminowicz says.
“This approach acknowledges that the sensory compon- ent of the pain is just that—one component. Along with that, you have the cognitive and emotional components, which can cause the suffering or disability that patients are most concerned with. In my lab, we study mostly non-pharmacological interventions. These could be anything from surgery to non-invasive brain stimulation to CBT,” he explains. “Essentially, all of these things work, if given to the right person, in the right dose, at the right time.” One treatment that Seminowicz and his colleagues have studied for migraine is mindfulness, which can include meditation and breathing exercises. In a clinical trial published in 2020, 98 adults with migraine were randomly assigned to one of two eight-week interventions: an enhanced mindfulness-based stress-reduction program or a stress-management program for headache.
Over 28 weeks from the start of the program, more than half of the mindfulness group experienced a 50 per cent reduction in headache days, compared with 23 per cent of the stress-management group. Participants in the mindfulness group also saw greater reductions in headache disability.
Breakthrough Medications
Sadly, medications aren’t a quick fix for chronic pain. “We always say the best drugs reduce pain by 30 per cent in 30 per cent of patients; the best we can ask for is 50 per cent of patients, depending on the type of pain,” Seminowicz says. That’s why “a single drug is never a total solution.” However, two relatively recent developments promise new treatment options for patients with certain conditions.
The first of an entirely new class of drugs for migraine was approved in 2018. (Several others are now available as well.) Referred to as anti-CGRP (calcitonin gene-related peptide) medications, these are lab-created proteins.
While CGRP is naturally present in the body, levels rise during an attack in people who experience migraines, which can cause the widening of blood vessels and inflammation that produces the pain. Anti-CGRP drugs block the release of CGRP. “They work as well as or better than some previous drugs but with essentially no side effects,” Seminowicz says.
Another development causing excitement among chronic-pain researchers and clinicians is the arrival of another brand-new class of pain medications called Nav1.8 inhibitors. Scientists have known for some time that a set of molecular “gates” known as sodium ion channels are involved in pain. Lidocaine, which is used for dental procedures, acts on sodium ion channels. However, since sodium ion channels also play critical roles in other important functions, including initiating the electrical signal that keeps the heart beating, the drawbacks of drugs that indiscriminately block sodium ion channels are obvious. After many years of research, which included studying families with members who are incapable of feeling pain, scientists finally homed in on a way to block one specific sodium ion channel that’s key to the trans- mission of pain signals.
Early in 2025, the US Food and Drug Administration approved the first sodium ion channel blocker specifically developed for pain. “It was approved for acute pain, but the expectation is that it’s going to work for chronic pain,” Seminowicz explains. One exciting aspect of Nav1.8 inhibitors is that, because of the way they work, they’re not expected to have the significant potential for abuse that Oxycontin—the last major drug approved for pain—turned out to have.
Prevention Strategies for Emerging Chronic Pain
“Prevention of chronic pain is where my group and several other groups have turned their attention recently,” Seminowicz says. Some researchers are studying whether interventions at the time of certain surgeries might reduce the likelihood that patients will be left with persistent pain long after the operation, which, unfortunately, is a relatively common complication.
For instance, approximately one in three women who undergo breast-cancer surgery are left with chronic pain. Teams of scientists from the University of Toronto are conducting trials to determine whether the use of a local nerve block during a lumpectomy or mastectomy can prevent this from occurring. Another group is doing a similar study for knee-replacement surgery. Other researchers are investigating whether a course of high-dose vitamin C before and after knee replacement can reduce the risk for subsequent chronic pain, as post-operative healing depletes this vitamin and many patients develop a deficiency.
Some scientists, including Seminowicz, are trying to devise ways to identify which people are most likely to graduate from acute to chronic pain, using tests that measure so-called biomarkers—substances or characteristics that indicate a state or condition. “My lab is focused on predictive biomarkers to identify who’s at risk, so we look at transition from acute to chronic pain, for example, in someone who hurts their back,” Seminowicz says.
“That’s important to know because we could potentially intervene early to prevent chronic pain.” You can also use biomarkers for other purposes, such as identifying who’s likely to respond to a treatment.
Predicting pain sensitivity is another area for study. “Typically whatever injury caused the pain is going to resolve in four to six weeks; pain that goes beyond that is considered persistent pain, and if that goes on for a few months, that becomes chronic pain,” Seminowicz explains. “Once you’re in that chronic-pain state, it’s very hard to treat. Currently, the best predictor that we have is pain severity at the onset of that injury.” Seminowicz and his colleagues have developed a method using data from EEGs—tests for measuring electrical activity in the brain— that they’ve tested and validated for this purpose. Healthy volunteers underwent the scans prior to receiving an injection that induces jaw pain for a few weeks. “With that metric alone, we were able to predict who would be high pain-sensitive and who would be low pain-sensitive.”
Another promising line of research is being led by Dr. Luda Diatchenko, Canada Research Chair Tier 1 in Human Pain Genetics and a professor in both the Faculty of Dental Medicine and Health Sciences and the Faculty of Medicine and Health Sciences at McGill University in Montreal. In one study, blood samples were taken from patients at the onset of an episode of acute back pain and again three months later. The researchers discovered that people whose pain resolved over that period “had a lot of activity of immune cells in their blood,” Diatchenko explains, adding that those who had pain that persisted “didn’t have any immune activity in their blood.” The finding was unexpected, she says. In fact, it was the opposite of what many scientists had suspected—that perhaps excess inflammation due to an overactive immune response was a driver of chronic pain. In a subsequent series of experiments, mice were given a chemical that typically induces inflammation and pain that resolves within less than a month. Half of the animals also received dexamethasone, a steroid that suppresses a broad range of immune activity and quashes inflammation and pain.
In the mice that didn’t get dexamethasone, pain behaviours lasted the typical three weeks. Those that did receive the steroid “had pain for over three months,” Diatchenko says. “You don’t see swelling or redness for a longer time, but you detect pain behaviour for much, much longer.” This suggests that other types of anti-inflammatory medications used to reduce pain in the short term might prolong it over the long term. It might be possible to determine at the time of injury whether someone’s immune system is mounting an adequate response, and if not, use a medication to boost immune activity.
This line of research may help explain why strategies known to reduce pain are effective. One common thread that connects physical therapy, exercise, and acupuncture, Diatchenko says, “is the neutrophil [a type of white blood cell] activation and physiological local inflammatory response” that occur in all three scenarios. Based on this work, Diatchenko believes “that we are equipped with all the tools we need to resolve pain” for all but the small fraction of the population with severe immune dysfunction.
