When we think about the immune system, we usually think about fighting infections. A cold, a wound, or an infection triggers an immune response designed to protect us and help the body recover. But your immune system does much more than fight germs - it is also constantly communicating with your nervous system. This relationship becomes particularly interesting when we look at pain.
What Does Your Immune System Have to Do with Pain?
Your immune system and nervous system are not separate systems working independently. They communicate with each other continuously.
When tissue is injured, immune cells are recruited to the area. These cells release chemical messengers called cytokines and chemokines, that help coordinate the inflammatory response. Some of these chemicals also interact with the nerves responsible for detecting potentially harmful stimuli, making them more sensitive, to protect the body from harm.
This is normal, a helpful part of healing and useful in the short term. If you cut your finger, for example, inflammation makes the area sore and sensitive. That encourages you to protect it while the tissues repair themselves. Inflammation and pain are part of the body's protective response.
The relationship becomes more complicated when immune activation persists or when the nervous system remains sensitive even after the original threat or injury has resolved.
But What Exactly Is Inflammation?
Inflammation is a coordinated biological response to something the body perceives as harmful with the intention to protect and heal. It can be triggered by injury, infection, tissue damage, autoimmune activity and other forms of cellular stress.
Acute inflammation is usually short-lived. Think about what happens after an ankle sprain. The area may become swollen, warm, tender and painful. These are signs of inflammation. Immune cells and inflammatory chemicals are involved in containing the damage and beginning repair – a really helpful response!
Chronic inflammation is different. When immune activation continues for a prolonged period, it can contribute to ongoing changes in tissues and the nervous system – the helpful response becomes unhelpful and gets stuck. This is what happens in chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and some autoimmune conditions. In these conditions, the persistent immune response is an important part of the disease process.
However, it is important not to assume that persistent pain automatically means persistent inflammation.
When Does Helpful Inflammation Become a Problem?
Inflammation becomes more complicated when the immune response does not settle appropriately or when the nervous system continues responding as though there is a threat.
In some conditions, this inflammatory signalling can be contributing to persistent pain. Research in chronic spinal pain, for example, has found moderate evidence of higher levels of inflammatory markers in the bloodstream, compared with healthy people. However, the relationship between these markers and how severe someone's pain is is much less clear.
This is important, because research also tells us that you can have evidence of inflammation without it explaining all of your pain, and you can have significant pain without evidence of ongoing systemic inflammation.
What About Pain That Continues After the Tissue Has Healed?
This is where the nervous system becomes particularly important.
Imagine that you sprain your ankle. Initially, there may be genuine tissue damage and inflammation.
Over time, however, the tissues heal but your pain does not settle. This does not necessarily mean the ankle is still damaged or inflamed.
The immune system may still be talking to the nervous system , making it more sensitive following an injury or period of persistent pain. This can alter how information from the body is processed and how strongly the brain responds to sensory signals.
This is one of the mechanisms involved in nociplastic pain.
It is possible for more than one mechanism to exist at the same time. Someone with arthritis, for example, may have ongoing inflammation, changes to the joint, and increased sensitivity within the nervous system.
Pain is rarely as simple as finding one mechanism and switching it off.
Can You Have Pain Without Inflammation?
The short answer is a resounding yes! Pain is not an inflammation detector. Many common persistent pain conditions do not involve significant ongoing tissue inflammation. For example, people with chronic low back pain may experience substantial pain despite having no evidence of an active inflammatory disease.
Similarly, in conditions such as fibromyalgia, research has identified differences in inflammatory and immune-related signalling in some patients, but the findings are complex and do not establish that inflammation is the sole cause of the pain.
What About Neuroinflammation?
You may have come across the term neuroinflammation. Broadly speaking, this refers to immune and inflammatory processes occurring within or around the nervous system.
Researchers are particularly interested in the role of glial cells (specialized neuroimmune cells) such as microglia and astrocytes. These cells help support the nervous system, but also actively contribute to changing how sensitive it is.
Experimental research has shown that these cells can influence pain signalling. Human research is beginning to provide evidence that neuroimmune changes may also occur in people with persistent pain. A 2024 review of human PET imaging studies found signals consistent with neuroimmune activation in several chronic pain conditions, including chronic low back pain, fibromyalgia and migraine. However, the authors emphasised that there are still important uncertainties about how these signals should be interpreted and what they mean clinically.
What Does Stress Have to Do With the Immune System?
When we are stressed, the brain communicates with the body's hormonal and autonomic (fight or flight) systems. These systems help the body respond to threat.
Similar to the immune response, short-term stress is not necessarily harmful. These responses are protective and help us respond to challenges. The problem is prolonged or repeated stress.
Research suggests that chronic psychological stress can alter the sensitivity of our immune system and can make our body environment more prone to inflammation.
The relationship between stress, the immune system and pain is important to understand. Persistent pain itself is stressful. Living with pain can affect sleep, activity, relationships, work, mood and sense of safety. These experiences can in turn influence the nervous, hormonal and immune systems. This creates the potential for a feedback loop:
Pain → stress → altered nervous and immune regulation → increased sensitivity → more pain
But the sequence can also have a different order:
Stress = altered nervous and immune regulation = pain = increased sensitivity = more stress = altered nervous and immune regulation = more pain.
That does not mean the pain is “in your head”. It means that the brain, immune system and body are communicating, as they are designed to do. The process may just have gotten stuck and starts to outlive its usefulness.
What About Sleep?
Sleep is another important part of this picture.
The relationship between sleep and the immune system is bidirectional. Sleep helps regulate immune function, while immune signalling can influence sleep. Persistent pain commonly disrupts sleep, and disturbed sleep may subsequently influence inflammatory and immune processes.
This is one reason why improving sleep can be worthwhile even when it doesn't directly “treat inflammation”.
Better sleep may help the nervous system regulate pain, improve energy and support overall health.
Can Lifestyle Choices Influence Inflammation?
Lifestyle does influence immune and inflammatory regulation.
Physical activity: Regular physical activity has complex effects on the immune system and is associated with benefits across many chronic conditions. Exercise may influence inflammatory signalling as well as the nervous system's ability to regulate pain. It also has other benefits including improving strength, fitness, sleep, mood and confidence in movement.
Sleep: Prioritising consistent, good-quality sleep supports immune regulation and overall health. If pain is interfering with sleep, addressing the pain-sleep relationship may be an important part of treatment rather than simply telling someone to “sleep better”.
Stress management: Stress cannot always be removed from our lives and telling someone with chronic pain to “just relax” is neither helpful nor realistic. Learning ways to regulate stress may help reduce the physiological effects of prolonged stress. This might include breathing exercises, mindfulness, psychological therapies, time outdoors, social connection, relaxation strategies, and activities that provide meaning and enjoyment.
Nutrition: A balanced dietary pattern supports general health and immune function. There is increasing interest in dietary patterns associated with lower systemic inflammation, including Mediterranean-style eating patterns. However, no single “anti-inflammatory food” or supplement should be considered a treatment for chronic pain. For most people, an anti-inflammatory way of eating is less about removing one item and more about what the overall pattern looks like across a week.
Smoking cessation: Smoking has well-established negative effects on health and is associated with inflammatory and immune changes. If you smoke, stopping can have substantial benefits for your overall health, even if pain does not disappear as a result.
How Do Healthcare Providers Treat Inflammatory Pain?
Treatment depends on why the inflammation is occurring.
If an inflammatory or auto-immune disease is present, treating the underlying disease is often central to management. Depending on the condition, treatment may include anti-inflammatory medicines, disease-modifying medications, biologic therapies, other condition-specific medicines, physiotherapy and exercise, occupational therapy, education and self-management, psychological support, and interventional treatments in selected circumstances.
As the relationships between the immune system, the nervous system, inflammation and stress are complex, treatment plans rarely include a single treatment option and must be developed specifically for the individual.
This is why identifying the different contributors to someone's pain is so important – to ensure the right treatment for the right patient at the right time.
Why Understanding Inflammation Can Change the Way You Think About Pain
Pain is not produced by a single system. The immune system, nervous system, stress system, endocrine system, musculoskeletal system and psychological and social environments constantly interact and contribute to generate the specific combination of symptoms someone may experience.
Inflammation may be one of the contributors to someone’s pain. In some conditions it is central to the disease process. In others, it may be present alongside other mechanisms. And in many persistent pain conditions, ongoing inflammation is not the primary explanation for why pain continues.
This is good news in one important respect. It means that there may be more than one way to influence pain.
If inflammation is contributing, treating the underlying inflammatory condition may help. If nervous system sensitivity is contributing, approaches that help regulate pain processing may be useful.
If poor sleep, stress, reduced activity, or loss of confidence in movement are maintaining the problem, these can also become targets for treatment.
Importantly, having pain does not mean that your body is broken or that your immune system is necessarily “out of control”. Your immune system and nervous system are constantly adapting to what is happening around you. If these systems have learnt to become more sensitive and on high-alert, they can also ‘unlearn’ and return to a state where they respond more appropriately.
Understanding that relationship can help us move away from simple explanations and towards care that is more personalised, evidence-informed and focused on helping you get back to the things that matter.