Editor’s Note: At the 2018 World Congress on Pain in Boston, the biennial meeting of the International Association for the Study of Pain (IASP), researchers from around the world gathered from September 12-16 to discuss the latest pain research. Twelve young scientists attending the World Congress were selected to provide first-hand reporting from the event, as part of the PRF Correspondents program, which is a science communications training program provided by the Pain Research Forum, RELIEF’s parent site. Here, PRF Correspondent Tory Madden, PhD, a postdoctoral research fellow at the University of Cape Town, South Africa, reports on a plenary lecture delivered at the meeting by Kathleen Sluka, a professor and pain researcher at the University of Iowa. (RELIEF’s news coverage is editorially independent of its publisher, IASP. All editorial decisions about our reporting on IASP activities are made solely by the RELIEF editors).
Isn’t it strange that rats and mice that are used for scientific research are housed in cages—effectively keeping them sedentary—even though the natural state of a rodent is to be physically active?
For years, scientists have studied physiology using sedentary animals, so they know a lot about what happens in the body when animals don’t move around much. They understand far less about what takes place in response to physical activity, but that’s beginning to change—and a whole world of knowledge is opening up.
It turns out that the physiology of physically active animals is quite different from that of sedentary ones. At last year’s International Association for the Study of Pain (IASP) World Congress on Pain in Boston, Kathleen Sluka, from the University of Iowa, described some of her research in this area, as well as findings from other groups. Her focus was on the implications of recent work in animals for the understanding and treatment of chronic pain in people.
Her message was straightforward, though perhaps contrary to expectations: exercise is actually a good thing for many people who have chronic pain.
When rodents run
Sluka and her colleagues noticed that, although physical activity guidelines recommend that adults should be active for at least 150 minutes each week, not many actually achieve that. Activity levels are particularly low amongst people who have chronic pain, since it is often assumed that exercise makes their pain worse.
But research indicates that people who are physically active are less likely to develop chronic pain than those who are sedentary. Also, exercise has repeatedly been shown to reduce pain and disability in people who already have chronic pain conditions—in fact, it’s the most highly recommended treatment for chronic pain.
Sluka and her team set out to tease apart the physiological differences between physically active and sedentary animals. They compared mice that were housed in cages with a running wheel—in which case they tend to spend much of the day engaged in voluntary wheel running, much like the average pet hamster—to mice that were housed in their usual cages without the running wheel.
The researchers used an experimental model in which they injured a muscle in both groups of animals. The muscle injury consistently evoked pain-related behavior (that is, behavior that scientists interpret as indicating that an animal is in pain) in sedentary animals—but it did not do so in physically active animals. This nicely matched the evidence from human research showing that the physically active have a lower risk of developing chronic pain.
Physical activity dampens danger signals
The next question to address was how physical activity protected the wheel-running mice against pain. The researchers found that, after muscle injury, physically active animals had more serotonin, a neurotransmitter that facilitates communication between nerve cells, than sedentary animals did. This might explain the differences in pain seen between active and sedentary animals since serotonin is known to dampen “danger signals” transmitted from injured bodily tissues towards the brain. These are the same signals that can contribute to pain.
Serotonin has its own specialized transporter, a type of protein, which removes the neurotransmitter from synapses, the spaces that nerves signal across. Removing serotonin increases danger signals and, typically, results in more pain.
Older studies in sedentary animals had shown that injury causes an increase in levels of the serotonin transporter, so Sluka’s team tested whether changes in this protein could explain why the physically active animals showed less pain-related behavior. They found that injuring physically active animals did not increase the amount of serotonin transporter, so there was still plenty of serotonin available in the synapses. This suggested that physically active animals don’t develop the same rampant danger signalling that their sedentary counterparts do.
And, when the researchers blocked the activity of serotonin, the physically active animals no longer showed less pain behavior in response to injury—they now looked just like their sedentary counterparts. All of this shows that physical activity regulates the serotonin system to protect against pain after muscle injury.
The cytokine connection
Next, Sluka turned the audience’s attention to cytokines. These are small proteins in the immune system that can increase or reduce inflammation to influence danger signalling in the body. Research has shown that physical activity alters the cytokine response to injury, with physically active animals showing less disruption of that response.
The cytokine system is usually held in a delicate balance, with cytokines that promote inflammation (pro-inflammatory cytokines) balanced out by those that oppose inflammation (anti-inflammatory cytokines). Broadly speaking, more inflammation is linked to more danger signalling.
Studies show that experimentally-injured sedentary animals have higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines than their physically active, injured counterparts. In the sedentary animals, blocking the activity of the pro-inflammatory cytokines with certain chemicals decreased the animals’ pain behavior. And, in the physically active animals, blocking the anti-inflammatory cytokines increased their pain behavior—they started to behave more like the sedentary animals.
What about people with chronic pain?
Regular physical activity clearly has beneficial effects on physiological systems. But all the studies described thus far looked at animals. What about the role of physical activity in people who have chronic pain?
With regard to the human situation, Sluka cited research from others that looked at people with fibromyalgia, a condition in which sufferers report pain in multiple body sites. Sedentary people who have fibromyalgia have more pro-inflammatory cytokine activity than people who don’t have fibromyalgia, which probably contributes to their pain.
In one study, sedentary people with fibromyalgia participated in a regular exercise program for a few weeks and looked at what that did to their cytokines. Cytokines levels of those who had become physically active were now similar to those of people without fibromyalgia. In short, physical activity had normalized their cytokine system.
This finding suggests an opportunity for people with fibromyalgia to influence their own physiology with an accessible, affordable, and even fun self-treatment—exercise! The type of exercise doesn’t seem to be particularly important. It’s more a matter of picking the type of exercise that is most enjoyable and accessible, and one that people are likely to do consistently over the long term.
The move to study physically active animals has propelled the scientific understanding of how physical activity influences pain and health. The natural state of rodents is to be physically active, and the same is true for people. It’s clear that physical activity improves physiological systems in multiple ways to protect against, or reduce, chronic pain.
It may be counterintuitive that exercise can improve pain, and exercise will indeed be too painful for some–that’s a very important caveat. But for chronic pain sufferers who can manage it, it’s time to lace up, call a friend, and get moving!
Tory Madden, PhD, is a postdoctoral research fellow at the University of Cape Town, South Africa.
See here for a related podcast with Sluka on the Pain Research Forum.