Your pain is real. Here is the biology that proves it. What fibromyalgia actually does to the nervous system, and why this changes everything about how we treat it. There is a info graphic at the bottom, for those who prefer visual info,.
Hi Friend,
Over the last two weeks I have told you that fibromyalgia is a disorder of pain processing rather than a disorder of muscles or joints, and that the nervous system arrives at a fibromyalgia diagnosis already shaped by years of earlier experience. Neural pruning, early stress, developmental windows. The architecture was set long before the symptoms became undeniable.
This week I want to tell you what is actually happening inside that nervous system right now. Not metaphorically. Not conceptually. Biologically.
Because one of the most damaging things that happens to people with fibromyalgia is being told, explicitly or implicitly, that their pain is not real. That the investigations came back normal therefore nothing is wrong. That it is stress, or anxiety, or something they need to work through rather than something that needs treating. This newsletter exists, in part, to give you the language to reject that framing completely. Because the biology does not support it.
What central sensitisation actually means
The term gets used a lot in fibromyalgia circles but it is rarely explained properly, so let me be precise.
In a healthy nervous system, pain signals travel from the site of a stimulus through the peripheral nerves and into the spinal cord, where they are processed and relayed upward to the brain. The brain then interprets the signal, contextualises it, and produces the experience of pain. The key word there is interprets. Pain is not a direct readout of tissue damage. It is a construction. The brain decides, based on a huge range of inputs, how threatening a signal is, and produces a pain experience proportional to its assessment of threat.
Central sensitisation is what happens when that assessment system gets stuck on high alert. The neurons in the spinal cord and brain that process pain signals become hyperexcitable. Their firing threshold drops. Signals that would not normally generate pain start generating it. Signals that would normally generate mild pain generate severe pain. The system has been turned up, and it cannot turn itself back down.
This is not imaginary and it is not psychological in the dismissive sense of that word. It is a measurable change in neuronal excitability. The neurotransmitters that amplify pain signals, including substance P and glutamate, are elevated in fibromyalgia. The neurotransmitters that dampen pain signals, including serotonin and noradrenaline, are reduced. The net effect is a nervous system that amplifies incoming signals and fails to suppress them adequately.
Wind-up: when the volume dial gets stuck
One of the most important phenomena in central sensitisation is something called wind-up. This is the process by which repeated stimulation of pain pathways causes progressively greater responses in the spinal cord, even when the stimulus itself stays exactly the same or even decreases.
Think of it like this. In a normal nervous system, if you press on a tender spot repeatedly, the pain response stays roughly consistent, or habituates downward as the brain decides the stimulus is not a genuine threat. In a sensitised nervous system, pressing on that same spot repeatedly causes the pain response to increase with each repetition. The system is not learning that the stimulus is safe. It is learning that the stimulus is dangerous, regardless of the actual evidence.
This is why fibromyalgia pain so often feels disproportionate to what is happening in the body. It is disproportionate, in the sense that the peripheral tissue is not generating signals that justify the response. But the response itself is completely logical given the state of the central processing system. The amplifier is broken, not the source signal. And treating the source signal, which is what most conventional medicine attempts to do, does almost nothing because it is the wrong target.
Glial cells and the inflammation nobody mentions
There is a component of fibromyalgia biology that has only become well understood in the last decade, and it rarely gets discussed in the conversations patients have with doctors. It involves the brain's immune cells, called glial cells, specifically a subset called microglia.
Microglia are the brain's resident surveillance system. Under normal conditions they monitor the neural environment and respond to injury or infection. Under conditions of chronic stress, chronic pain signalling, or sustained threat, they become activated. And activated microglia release inflammatory cytokines directly into the central nervous system, creating a state of neuroinflammation that further lowers the pain threshold and contributes to the cognitive symptoms of fibromyalgia, including brain fog, word-finding difficulties, and difficulty with concentration.
This is why fibromyalgia is not just a pain condition. The neuroinflammation produced by activated microglia affects the brain broadly. The fatigue, the cognitive symptoms, the mood disturbances, and the sleep disruption are not separate problems that happen to accompany the pain. They are downstream consequences of the same central biological process. Treating them as unrelated symptoms requiring separate treatments is understandable given how medicine has historically been organised, but it is not accurate.
Why sleep disruption is not just a symptom
Most fibromyalgia patients report significant sleep disruption, and most explanations treat this as a consequence of pain. Pain keeps you awake, therefore you are tired. That is true as far as it goes, but the relationship is considerably more bidirectional than that framing implies.
Restorative sleep, specifically the deeper stages of non-REM sleep, is when the nervous system performs a critical maintenance function. Inflammatory mediators are cleared. Pain processing pathways are recalibrated. The threshold at which signals get amplified is reset downward. When deep sleep is disrupted repeatedly, this recalibration does not happen. The pain threshold stays low. The amplification stays high. The neuroinflammation that built up during waking hours is not adequately cleared.
In fibromyalgia, sleep disruption and central sensitisation form a loop that is almost impossible to exit without directly addressing the sleep architecture, not just the pain. This is one of the reasons that low dose naltrexone and certain tricyclic antidepressants, used in low doses for their effects on sleep architecture rather than depression, can produce meaningful improvement. They are not just treating symptoms. They are interrupting a biological cycle that is self-sustaining.
What this means for treatment
All of the above points to the same conclusion. Fibromyalgia cannot be treated effectively with interventions that target peripheral tissue, because the peripheral tissue is not the primary problem. Anti-inflammatories, repeated imaging, injections, surgery, and passive physical therapies have poor outcomes in fibromyalgia for precisely this reason. They are addressing the wrong level of the system.
Effective treatment targets the central mechanisms directly. This means approaches that reduce neuroinflammation. That downregulate the activity of overexcited pain pathways. That restore the sleep architecture that allows nightly recalibration. That help the nervous system accumulate evidence, over time and through carefully managed experience, that it is not in the danger it believes itself to be in.
This is why pacing is not rest. Why certain medications work when others do not. Why psychological approaches like pain neuroscience education and graded activity produce measurable biological changes rather than just attitude shifts. The treatment map follows the biology, and once you understand the biology, the treatment map starts to make sense.
Next week I will begin to map that treatment landscape in detail: what the evidence actually supports, what is overhyped, and how to think about building a personalised approach when so many of these conditions look similar from the outside but require very different strategies depending on the individual picture.
A new way to get personalised input
Understanding the biology is one thing. Understanding what it means for your specific body, your specific history, and your specific path forward is another.
The Mend Chronic Illness Roadmap Service is designed for exactly that gap. You send me your full history, your results, and a detailed questionnaire about your symptoms, your timeline, and everything you have already tried. I review everything and produce a comprehensive, individualised clinical report covering what I believe is driving your picture, what investigations would be meaningful, and what a structured treatment approach would look like for you specifically.
If you have never had someone sit with your whole story and make sense of it as a single coherent picture rather than a collection of disconnected diagnoses, this is what the service is built for.
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Stay well,
Dr Ahmed
This newsletter is for educational purposes only and does not constitute medical advice. The information shared here is intended to help you understand your condition more deeply, not to replace the guidance of a qualified clinician who knows your individual history. If you have concerns about your health, please speak to your doctor or specialist.
