##PAIN SCIENCE
Your bloodwork is clean and you still hurt. That is not a contradiction.
#Pain and inflammation are two different systems, and treating the disease well does not always switch the pain off. Here is why, and what to do about it.
Week of September 11, 2026. Angelo Papachristos PT, ACPAC. RheumAcademy | Arthros Inc.
A woman in her fifties with rheumatoid arthritis came to clinic with a small notebook. Her joints looked quiet, her inflammatory markers were low, her rheumatologist was pleased. And she was exhausted from hurting. Her question, written at the top of the page so she wouldn't lose her nerve, was this: if the disease is controlled, why does my body still feel like this, and does that mean I'm making it up?
There is more than one kind of pain, and rheumatology involves all of them
The oldest and most intuitive kind is nociceptive pain. You stub your toe, a nerve ending fires, the signal travels up, you feel it. It is the alarm doing its job, roughly in proportion to the damage. Mechanical joint pain from worn cartilage in osteoarthritis lives mostly here.
Then there is inflammatory pain. When the immune system floods a joint with cytokines, those chemical signals turn the alarm sensitivity way up. The joint hurts more, sooner, and at rest, because the tissue is chemically irritated. This is the pain your DMARDs and biologics are built to switch off, and when they work, this component often melts away over weeks.
The third kind is the one almost nobody explains, and it is the one that answers my patient's notebook question. In 2016 a group of pain researchers led by Kosek proposed a formal name for it in the journal Pain: nociplastic pain. The idea is that the nervous system itself, the spinal cord and brain that process pain signals, can become turned up and stay turned up, so that pain is generated and amplified even when there is little or no ongoing tissue damage to explain it. The alarm has become oversensitive. Nothing is on fire, but the smoke detector goes off at a candle.
Why the pain can outlast the inflammation
This is not a rare footnote. In rheumatoid arthritis, a meaningful minority of people reach good inflammatory control and still live with pain that the disease activity does not explain. Altawil and colleagues, looking at early RA patients treated with methotrexate in Arthritis Care & Research in 2016, found that a real fraction were left in an unacceptable pain state despite their inflammation settling. The tender joint count and the CRP had done what they were supposed to. The pain had not read the memo.
Why? Because pain that has been loud for a long time changes the machinery that carries it. Lee and colleagues laid this out clearly in Arthritis Research & Therapy in 2011, describing how the central nervous system contributes to chronic pain across rheumatoid arthritis, osteoarthritis and fibromyalgia. The same central amplification shows up when you test it directly. Arendt-Nielsen and colleagues, in Pain in 2010, put people with painful knee osteoarthritis through quantitative sensory testing and found their nervous systems were more sensitised, more responsive to pressure and repeated stimulation, than you would predict from the state of the cartilage alone. The joint was part of the story. The spinal cord was the rest of it.
There is also a good deal of overlap between inflammatory arthritis and fibromyalgia-type widespread pain. When the two travel together, standard disease activity scores like the DAS28 can read as 'active' partly because of tender joints and patient-reported pain that are being driven by this central sensitivity rather than by swelling. That can push a treatment decision toward escalating immunosuppression that was never going to touch the real driver.
"It's all in your head" is the wrong reading, and it costs people
When I explained central sensitisation to my patient with the notebook, the relief on her face was not because I had told her the pain was imaginary. It was the opposite. I was telling her that her pain was real, produced by a real and measurable change in a real physical system, her nervous system, and that this change had a name and an evidence base. The itching alarm in her hands was not a character flaw or a sign she was weak. It was a nervous system that had been on high alert for years and had learned to stay there.
The phrase 'it's all in your head' does damage because it forces a false choice: either the pain is in the tissue and therefore real, or it is in the mind and therefore not. Central sensitisation refuses that choice. The brain and spinal cord are tissue. Pain that is generated centrally is as real as pain generated at a hot stove. What changes is the treatment, because you cannot fix an oversensitive alarm by pouring more medication on a joint that isn't inflamed.
What actually helps a sensitised system settle
The first thing that helps is understanding, and I mean that as an intervention, not a platitude. Teaching people how pain is produced, what sensitisation is, and why hurt does not always equal harm, is called pain neuroscience education. Louw and colleagues reviewed the trials of it in Archives of Physical Medicine and Rehabilitation in 2011 and found that when people understand their pain differently, they move more, fear it less, and function better. Moseley and Butler, reflecting on fifteen years of this work in the Journal of Pain in 2015, made the point that changing what pain means to a person changes how much it threatens them, and a less threatened nervous system is a less amplified one.
The second thing is graded activity. Not resting the pain away, and not pushing through until you flare, but a gradual, planned increase in movement that gives the nervous system repeated, safe evidence that activity is not dangerous. This is where a physiotherapist earns their keep, setting a baseline you can manage on a bad day and building from there in increments small enough that your alarm doesn't panic. Sleep, mood and stress feed directly into pain sensitivity too, which is why the sensitised system so often improves fastest when those are addressed alongside the movement, rather than after it.
Medications for this kind of pain are a different toolkit from the ones aimed at inflammation. Agents that act on the central nervous system, the kind sometimes used in fibromyalgia, are what a rheumatologist reaches for here, not more biologic. That is a conversation to have deliberately, because the right drug for inflammatory pain is often the wrong drug for nociplastic pain, and vice versa.
What to do, and the conversation to have
If your disease markers are good and you still have significant pain, name it out loud at your next visit and ask your team directly which kind of pain they think is driving it. The most useful question you can bring is whether your current pain reflects active inflammation or a sensitised nervous system, because the answer changes the plan. If it is the latter, ask for a referral for pain neuroscience education and a graded activity program with a physiotherapist, and ask whether a centrally acting pain medication is worth trying. Bring the notebook. A record of when the pain is worse, what you were doing, and how you slept is more useful to us than a single number on the day.
Questions for your care team
- Given my inflammatory markers, how much of my current pain do you think is coming from active disease versus a sensitised nervous system?
- Would pain neuroscience education and a graded activity program with a physiotherapist be appropriate for me?
- Is a centrally acting pain medication worth considering, rather than escalating my immunosuppression, for this kind of pain?
- Between visits, what should I track: I am planning to log pain alongside activity and sleep rather than pain alone. Is that the right thing to bring back?
What this does not mean
None of this is a reason to stop or reduce your disease-modifying medication on your own. Controlling inflammation still protects your joints and organs whether or not it fully controls your pain, and understanding central sensitisation is meant to add a second front to your treatment, not remove the first one.
References
Kosek 2016 - nociplastic pain third descriptor. Kosek E, Cohen M, Baron R, et al. Do we need a third mechanistic descriptor for chronic pain states? Pain. 2016;157(7):1382-1386.
https://pubmed.ncbi.nlm.nih.gov/26835783/
Altawil 2016 - remaining pain in early RA on methotrexate. Altawil R, Saevarsdottir S, Wedren S, et al. Remaining Pain in Early Rheumatoid Arthritis Patients Treated With Methotrexate. Arthritis Care & Research. 2016;68(8):1061-1068.
https://pubmed.ncbi.nlm.nih.gov/26784398/
Lee 2011 - central nervous system in chronic pain in RA/OA/fibromyalgia. Lee YC, Nassikas NJ, Clauw DJ. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arthritis Research & Therapy. 2011;13(2):211.
https://pubmed.ncbi.nlm.nih.gov/20851023/
Arendt-Nielsen 2010 - sensitization in painful knee osteoarthritis. Arendt-Nielsen L, Nie H, Laursen MB, et al. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149(3):573-581.
https://pubmed.ncbi.nlm.nih.gov/20418016/
Louw 2011 - systematic review of pain neuroscience education. Louw A, Diener I, Butler DS, Puentedura EJ. The effect of neuroscience education on pain, disability, anxiety, and stress in chronic musculoskeletal pain. Archives of Physical Medicine and Rehabilitation. 2011;92(12):2041-2056.
https://pubmed.ncbi.nlm.nih.gov/22133255/
Moseley 2015 - fifteen years of explaining pain. Moseley GL, Butler DS. Fifteen Years of Explaining Pain: The Past, Present, and Future. The Journal of Pain. 2015;16(9):807-813.
https://pubmed.ncbi.nlm.nih.gov/26051220/
This article is for education only and is not medical advice. It cannot account for your individual diagnosis, medications, or circumstances. Decisions about your treatment should be made with your own rheumatology team, who know your history.
Angelo Papachristos PT, ACPAC. Advanced Practice Physiotherapist. Co-Founder, RheumAcademy. Co-Founder, Arthros Inc.