Multiple sclerosis and pain are closely connected for many people living with MS, but chronic pain does not automatically mean that something in the body is being damaged again and again.
In this episode of the MS-Perspektive Podcast, Nele talks with Rasmus Christian Jungersen, PhD student at Aarhus University in Denmark, about pain in MS, the different pain types, and how exercise and physical activity may help. His most important message is empowering: movement is not the enemy. When pain is chronic, exercise does not usually worsen an injury. Instead, it may become part of a broader strategy to reduce pain and improve quality of life.
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Introduction Rasmus & Context
Could you briefly introduce yourself and your work at Aarhus University?
Rasmus Christian Jungersen, PhD student: My name is Rasmus Christian Jungersen. I am from Aarhus in Denmark, where I am a PhD student at the Department of Exercise Biology.
I am part of a research group that focuses on exercise as medicine, especially for people with neurodegenerative disorders such as Parkinson’s disease and multiple sclerosis. My own specialty is MS, particularly pain in MS.
Pain is a symptom that can take up a lot of space in people’s lives. It can affect quality of life, sleep, fatigue, mood, and everyday activities. My research focuses on how we can reduce pain and reduce the impact pain has on quality of life through exercise.
We look at long-term exercise, for example what happens when participants train for three months. But we also look at the short-term effect of just one exercise session. We measure pain thresholds and subjective pain before and after exercise.
Another important part of my research is that pain is not just pain. Especially in MS, pain is very complex. We try to identify the different pain types, or pain phenotypes, and investigate whether exercise has different effects depending on the type of pain a person experiences.
When we talk about pain in multiple sclerosis, what different types of pain are we referring to?
Rasmus Christian Jungersen: In MS, we can generally divide pain into two broad categories: directly related MS pain and indirectly related MS pain.
Directly related MS pain is usually called neuropathic pain. Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. That is the part of the nervous system responsible for sensory inputs such as touch, pain, and temperature.
In MS, people have lesions in the central nervous system. Therefore, when we talk about neuropathic pain in MS, we usually mean central neuropathic pain.
There are different subtypes of neuropathic pain. One example is trigeminal neuralgia. This can be very severe and is usually located in the face. It often occurs in bursts and can be triggered by things like wind or even a piece of hair touching the face.
Another example is Lhermitte’s phenomenon. This is an electric-shock-like pain or sensation that runs down the spine when a person bends the neck. It is likely linked to lesions in the cervical area of the spinal cord.
The most common type of neuropathic pain is neuropathic extremity pain. This may feel sharp, burning, tingling, or like pinpricks, often in the legs, but also in the arms.
Then we also have indirectly related MS pain, which is often nociceptive pain. Nociceptive pain means that pain receptors in the body are activated. This type of pain is often musculoskeletal. For example, it can be low back pain due to reduced mobility or an altered walking pattern. It can also be pain related to spasticity, because spasticity can create mechanical stress on the muscles.
There is also a third type of pain called nociplastic pain. But in MS, I would argue that it is very difficult to diagnose nociplastic pain, because nociplastic pain is defined as pain in the absence of clear neuronal or non-neuronal injury. In MS, there is by definition damage in the central nervous system. So we cannot exclude that at least part of the pain is neuropathic.
Migraine and headaches are also common in people with MS, especially in people with relapsing-remitting MS. The mechanisms are less clear, but migraine and headache are definitely relevant when we discuss pain in MS.
Scientific background: A mechanism-based classification by Truini and colleagues distinguishes several MS-related pain syndromes, including trigeminal neuralgia, Lhermitte’s phenomenon, ongoing extremity pain, painful tonic spasms, spasticity pain, musculoskeletal pain, migraine, optic neuritis-related pain, and treatment-induced pain.
How common is pain among people with MS?
Rasmus Christian Jungersen: Pain is very common in MS. It is estimated to be present in about 50 to 80% of people with MS.
We recently conducted a cross-sectional study in Denmark with around 1,000 participants. In that survey, about 80% of the participants reported pain. Of course, we have to take into account that if a questionnaire is about pain, people who suffer from pain may be more likely to answer it. So the real number may be somewhat lower.
A meta-analysis from a few years ago estimated pain to be present in around 60% of people with MS. So pain is a very big problem. And when it is present, it can have a huge impact on quality of life, sleep, fatigue, and other areas of daily life.
Which types of pain are seen most frequently in clinical practice and research?
Rasmus Christian Jungersen: When studies use questionnaires such as DN4 or PainDETECT, they often distinguish between neuropathic and nociceptive pain. But nociceptive pain is sometimes diagnosed simply by excluding neuropathic pain, which is not the best method.
When we look at pain in more detail, many people with MS experience more than one type of pain at the same time. This co-occurrence is very important. For example, someone may have trigeminal neuralgia and spasticity-related pain at the same time.
This matters because if we want to treat pain successfully, we need to understand what type of pain we are treating. That applies to medication, but also to exercise.
Spasticity-associated pain is one of the more common pain types. Neuropathic extremity pain is also very common. This is often also described as dysesthetic extremity pain. But overall, I would say that co-occurring pain — having more than one type of pain — is probably the most frequent situation.
Further reading: A recent mixed-methods study by Dagnew and colleagues looked at pain types and lived experiences in people with MS. It supports the point that MS pain is often not just one single pain type. Dysesthetic extremity pain and spasticity-associated pain were among the most frequently reported pain types.
What are the main mechanisms behind pain in MS, and why can pain differ so much from one person to another?
Rasmus Christian Jungersen: One aspect is lesion location. Where lesions are located may affect where a person experiences pain and what type of pain they experience. But that is only one part of the story.
In neuropathic pain, one important mechanism is central sensitization. This means that the pain system in the central nervous system becomes hypersensitive. Normally, touch does not hurt. But if the nervous system becomes sensitized, even light touch may be painful.
Neuroinflammation is also important. In the central nervous system, we have different support cells, such as astrocytes, oligodendrocytes, and glial cells. In MS, these systems can become overactive. That may contribute to inflammation in the nervous system, and this is believed to be strongly linked to chronic pain.
There may also be changes in neurotransmitters. Neurons communicate with each other through chemical messengers. If this communication is disrupted, pain perception may increase.
For nociceptive pain, the mechanisms are often more related to peripheral pain receptors. These can be activated by mechanical stress, heat, cold, inflammation, or other stimuli. In MS, systemic inflammation may make these pain receptors more likely to become activated.
Spasticity-related pain is different again. It can be caused by mechanical stress on muscles, cramps, or increased muscle tone.
So the reason pain differs so much from person to person is that the mechanisms behind the pain can be very different. And depending on the mechanism, the pain experience also differs.
Exercise and Pain Reduction
What do we currently know about the relationship between exercise and pain reduction in people with MS?
Rasmus Christian Jungersen: The research suggests that exercise may have a positive effect on pain in people with MS, but there are still major gaps.
Some studies have found that people who experience more pain are less physically active. However, in a recent study we conducted, we did not find a clear association between pain intensity and the amount of exercise or physical activity.
That may be because pain intensity is not the whole story. Sometimes the most important question is not only how intense pain is, but how much it interferes with sleep, mood, movement, and daily life.
Some people are very good at coping with pain, while others are not. So two people may report the same pain intensity, but the impact on their lives can be very different.
Pain can become a barrier to physical activity. If people interpret pain as injury, they may avoid movement. This is called fear-avoidance behavior. It is understandable, but in chronic pain it can become a problem, because inactivity may increase pain over time.
It is important to understand that chronic pain is different from acute injury pain. When pain is chronic, movement and exercise do not usually worsen the pain in the long term. In fact, exercise may help reduce pain and reduce the impact pain has on everyday life.
Research context: A systematic review and meta-analysis found some evidence that exercise interventions may reduce pain in people with MS compared with passive control groups. However, the authors also emphasized that the included studies were heterogeneous and often limited in quality, which fits Rasmus’ cautious interpretation of the current evidence.
What are the most important biological or psychological mechanisms through which physical activity may help reduce pain?
Rasmus Christian Jungersen: First, we need to understand what pain is. Pain is not just a sensory experience. It is also an emotional experience. It is influenced by sensory input, emotions, context, and the brain.
On a biological level, exercise may reduce systemic inflammation. If pain is partly driven by inflammation and activation of peripheral pain receptors, reducing inflammation may help reduce pain.
Exercise may also reduce spasticity. If pain is related to spasticity, then reducing spasticity may reduce pain.
Another important benefit of exercise is improved physical function. If a person has reduced mobility or an altered walking pattern, they may compensate in ways that create stress on muscles and joints. Exercise can improve strength, gait, balance, and mobility. This may reduce musculoskeletal pain.
For neuropathic pain, the evidence is more exploratory. Much of it comes from animal models. But exercise may reduce neuroinflammation, influence glial cell activity, improve brain connectivity, and reduce oxidative stress.
Oxidative stress means that there is an increased amount of reactive oxygen species. These molecules can affect tissue and nerve health. Exercise can improve the body’s ability to deal with oxidative stress.
Another interesting mechanism involves myokines. When muscles contract, they release signaling molecules into the bloodstream. These myokines can affect brain health. This may be one reason why exercise is beneficial in neurological diseases, and it may also be relevant for pain.
On a psychological level, exercise may reduce anxiety and depression. Chronic pain, anxiety, and depression are closely connected, and the relationship is probably bidirectional.
Exercise can also reduce fear-avoidance behavior. If someone is afraid of movement because they think movement will worsen pain, they may avoid activity. But inactivity can increase pain. Gradual exposure to movement can help break this cycle.
And finally, exercise can be a powerful distraction. Pain can be modulated by the brain. If movement redirects attention and gives the brain another task, pain may become easier to handle.
Mechanisms in focus: Research on exercise and chronic pain suggests several possible pathways, including effects on inflammation, oxidative stress, neuroplasticity, and descending pain modulation. These mechanisms are still being studied in MS, but they help explain why exercise may influence pain beyond muscles and joints.
Which forms of exercise appear to be particularly helpful for pain management in MS?
Rasmus Christian Jungersen: Right now, the evidence does not clearly show that one exercise type is better than another for pain in MS.
Studies are very heterogeneous. Some look at yoga, some at aerobic exercise, some at resistance training, and many combine different modalities. So it is difficult to compare them directly.
But I actually think this is good news. It means that people do not necessarily have to choose one specific type of exercise. They can choose what fits their life and what they enjoy.
If someone does not like going to the gym, they do not necessarily have to do resistance training in a gym. They could go for a walk, play badminton, swim, cycle, or do another activity they enjoy.
There is evidence from other chronic pain populations, such as people with low back pain, that even brisk walking can reduce pain. So the most important thing is to find something sustainable.
Combining different types of exercise, for example aerobic and resistance training, may also be useful and can help meet general exercise recommendations.
Does the effectiveness of exercise depend on the type of pain, such as neuropathic pain versus musculoskeletal pain?
Rasmus Christian Jungersen: That is a very interesting question, and it is actually one of the questions I am trying to answer in my PhD research.
At the moment, we do not yet have clear MS-specific evidence. But based on existing research, exercise seems to have a good effect on musculoskeletal pain. For nociceptive pain, the evidence is quite substantial.
For neuropathic pain, the picture is less clear. There are good indications, but the evidence is more limited, and much of it comes from animal studies.
Animal studies can give useful indications, but they also have clear limitations. Animals do not have the same physiology as humans. It is also difficult to define what “exercise” means in animals. And it is difficult to assess pain in animals because we cannot ask them to rate their pain.
So for musculoskeletal pain, we have stronger evidence. For neuropathic pain, we need more human research.
For musculoskeletal pain: Evidence from chronic musculoskeletal pain research supports exercise as an effective, safe, and low-cost therapeutic option. This is not the same as proving the effect for every type of MS pain, but it strengthens the rationale for exercise when MS pain is partly related to muscles, joints, posture, gait, or reduced mobility.
Practical Guidance for Patients
Should people ideally begin exercising under the guidance of a physiotherapist or exercise specialist, or can many patients safely start on their own?
Rasmus Christian Jungersen: It depends on the person’s disability level, previous experience with exercise, and the type of exercise they want to do.
If someone wants to start progressive resistance training, it may be a good idea to consult a professional and create a structured program.
But if someone has previous experience, for example they used to play badminton and want to start again, they may not necessarily need guidance.
If someone is very new to exercise, I would recommend consulting a professional in MS rehabilitation. That can help create a structured program and make the exercise safer and more effective.
What does a realistic exercise program look like in terms of frequency, duration, and intensity for someone who wants to reduce pain?
Rasmus Christian Jungersen: Gradual exposure is key. Start with low intensity and small challenges, then build from there.
It is okay to experience some pain while exercising, but it should disappear afterwards. If pain increases during exercise but settles again, that is not necessarily a problem. But you do not want to aggravate pain too much.
There is no clear evidence yet for one exact dose-response relationship between exercise intensity and pain reduction. But there is evidence supporting light to moderate exercise for pain reduction.
So people do not have to do very intense exercise if their main goal is pain relief. Light to moderate exercise can be sufficient.
In terms of frequency and duration, it may be more important to exercise more often than to have very long individual sessions. For example, half an hour several times per week may be better than one or two very long sessions.
What are realistic expectations regarding pain improvement, and how long does it typically take before benefits may become noticeable?
Rasmus Christian Jungersen: People should not expect an immediate long-term effect. You usually need to exercise for some time before long-term benefits become noticeable.
Studies have shown positive effects in programs lasting from one month up to six months. But we do not yet have a precise answer for how long it takes.
There may also be an acute effect after a single exercise session. In the general population, exercise can increase pain thresholds. This is called exercise-induced hypoalgesia. It may be linked to endorphins, which are the body’s own pain-inhibiting substances.
However, in people with MS, especially those with neuropathic pain, pain may sometimes increase immediately after exercise. In my own pilot work, we have seen that some participants experience a transient increase in pain after training.
The important message is that this increase is usually temporary. It may disappear after a while. It does not necessarily mean that the exercise is harmful.
In MS, symptoms can also temporarily worsen with heat or exertion. This is called Uhthoff’s phenomenon. It is not dangerous, but people should know that it can happen.
How should exercise be adapted for people who already have significant mobility limitations or permanent disability due to MS?
Rasmus Christian Jungersen: This is a limitation in much of the exercise research, because many studies focus on people with mild to moderate disability.
But exercise can be feasible and safe for people with more severe disability. It just needs to be adapted.
For example, in resistance training, some exercises require balance. If a person has reduced mobility or balance problems, a trainer or physiotherapist may need to provide support or adapt the movement.
There are also special exercise options for people who use a wheelchair. For example, some systems allow a wheelchair to be attached to a cycling device. Electrical stimulation can help activate the leg muscles, even if voluntary movement is reduced.
Telerehabilitation is another promising option. This means that physiotherapy or training is delivered online or by phone, allowing people to exercise from home. This can be helpful for people who cannot easily travel to a rehabilitation center.
For people with more severe disability, professional guidance is especially important. Exercise is still possible, but it often needs more adaptation and supervision.
Prevention and Long-Term Perspective
To what extent can regular physical activity help prevent pain problems from developing or worsening over the long term?
Rasmus Christian Jungersen: There is no direct evidence on this question yet.
But we do see that inactivity is highly correlated with pain, and inactivity can worsen pain symptoms. So being generally physically active may help prevent pain from occurring or worsening.
Based on the mechanisms we discussed, exercise may help by keeping neuroinflammation down and keeping the pain system from becoming too sensitive. But at this point, that is still more of a hypothesis than proven evidence.
What are the most common myths or misunderstandings about exercise and pain in MS that you would like to challenge?
Rasmus Christian Jungersen: The myth is that pain equals injury, and that exercise will worsen that injury. Because of this, people may think they should avoid exercise and physical activity.
But when we talk about chronic pain, any tissue damage that may have been there has usually healed. So you do not worsen pain by exercising. You do not worsen pain by being more physically active.
I think this is the key message people should take away: chronic pain does not automatically mean that movement is damaging your body.
Looking Ahead
Which development in the field of MS would you most like to see over the next five years?
Rasmus Christian Jungersen: First, we need to confirm the effect of exercise on pain in MS.
But we also need to understand the different variables of exercise. Exercise is many things. If exercise is medicine, we need to know what is in the pill.
Which modality is best? Which frequency? Which intensity? Which duration? How should exercise be prescribed?
And finally, we need to distinguish between pain phenotypes. We need to be able to recommend exercise based on the particular type of pain a person experiences.
Rasmus is currently involved in the EXpain project, which investigates whether exercise can be used as a non-pharmacological analgesic treatment for people with MS. This is exactly the kind of research needed to understand which exercise prescription works best for which pain phenotype.
Quickfire Q&A
What is the most important message about chronic pain and exercise?
Rasmus Christian Jungersen: Chronic pain does not automatically mean injury, and exercise does not usually worsen chronic pain in the long term.
Does exercise have to be intense to help with pain?
Rasmus Christian Jungersen: No. Light to moderate exercise may already be helpful.
Is one type of exercise best for MS pain?
Rasmus Christian Jungersen: We do not know that yet. Choose an activity that fits your life and preferences.
Can pain increase during exercise?
Rasmus Christian Jungersen: Yes, sometimes. But if it settles afterwards, it is not necessarily harmful.
Should people with severe disability still consider exercise?
Rasmus Christian Jungersen: Yes, but it should be adapted and ideally guided by a professional.
Farewell
What would you like to leave our listeners with regarding pain, movement, and living well with MS?
Rasmus Christian Jungersen: It is important to be realistic. With pain, we may not be able to completely remove it, but we may be able to reduce it substantially.
In pharmacological pain treatment, a successful treatment is often defined as a pain reduction of 30 to 50%. I think that is a realistic expectation.
But exercise is not the only solution. Pain is complex, so it needs a holistic approach. That may include psychological treatment, such as cognitive behavioral therapy, education about chronic pain, exercise, and sometimes pharmacological treatment.
Combining these approaches will likely optimize pain management. Even if pain does not disappear completely, it can become easier to live with.
Related episode:
Holistic approach for pain management: The Art of Pain Relief. Multimodal Approaches to MS (with Dr. Camelia Ionescu)
See you soon and try to make the best out of your life,
Nele
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