Pain without a lesion

The imaging is clear. The report uses words we have all come to find reassuring: unremarkable, within normal limits, no acute findings. The anatomy is intact; there is nothing to biopsy or to excise. There is nothing to fix.And yet the pain persists. She does not look dramatic or unstable. She looks tired. Tired of repeating the story. Tired of feeling as though relief hovers just one test away. Tired of trying to reconcile two competing truths: that her body hurts, and that nothing appears wrong.Normal results are, in many ways, one of medicine’s quiet triumphs. They signal absence of malignancy, disease or inflammatory destruction. They allow us to close certain doors with confidence. But occasionally, they open another kind of uncertainty: the space that exists when symptoms continue without visible cause.It is in that space that many of our patients live.Over the past decade, research has begun to clarify how the nervous system itself can become abnormally sensitized. Signals that were once tolerable begin to register as painful. Sensory input is amplified and confused. Recovery from ordinary stimuli takes longer. The volume control is turned up, not because the tissue is damaged, but because the circuitry processing it has fundamentally changed.Medicine has a language for tumours and tears. However, we are still refining our language for dysregulation.Central sensitization, and the broader concept of nociplastic pain, describes this altered processing. Pain exists without clear structural injury. People suffer without a diagnosable lesion. The symptoms are not imagined or exaggerated but generated within a system that has learned to amplify.And it doesn’t end with pain. Nervous system amplification can also shape sleep, mood, autonomic tone, and attention. A sensitized nervous system does not localize its effects neatly. It spills across multiple domains.A nervous system does not become sensitized in isolation. Sometimes the trigger is physical: an injury, a surgery, an infection, a period of sustained inflammation. Although tissue heals, the sensory signaling does not entirely reset. The pathways that were once protective remain on alert. The threshold for pain perception lowers and what began as an adaptive response lingers beyond its usefulness. At other times, the precipitant is less visible. Prolonged stress or repeated threat of environments in which vigilance was necessary. The body, remarkably loyal to survival, learns to scan, to brace, to anticipate or to freeze. The autonomic nervous system shifts toward readiness and protection. Therefore, recovery slows and signals feel louder.The brain does not distinguish sharply between physical and emotional threat. Both travel through overlapping circuitry. The amygdala, the anterior cingulate cortex and the insula are the regions responsible for interpreting danger, modulating pain and assigning meaning to sensation. When those networks are repeatedly activated, they adapt. The result is increased pain sensitivity with a complimentary decrease in inhibitory buffering.This does not imply fragility of the nervous system. It reflects plasticity. The nervous system changes in response to experience; whether that experience is a fractured vertebra, a complicated childbirth, a car accident or years spent in environments where safety was uncertain. Central sensitization, viewed through this lens, is less mysterious. It is the physiology of adaptation carried forward.And when we encounter patients whose symptoms exceed what imaging can explain, it may not be because nothing happened. It may be because something did happen and the system remembers. In these cases, pain is not solely a signal from tissue. It is also a signal from history.When dysregulation goes unrecognized, the clinical course often follows a familiar arc. We repeat investigations, hoping clarity will emerge with greater resolution. We adjust medications, sometimes targeting medical processes that are no longer (or never were) primary drivers. We refer across specialties, each encounter narrowing its focus to a particular organ system. Our work is earnest. The intention is to help, but the patient may leave feeling fragmented.When symptoms do not align neatly with visible pathology, explanations can become provisional. Stress is invoked. Anxiety is considered. The absence of structural findings can, unintentionally, begin to shape the narrative more than the persistence of suffering.Over time, this circular process can carry its own consequences. Trust thins and patients begin to doubt their own internal signals. Clinicians may feel frustration or fatigue. The therapeutic relationship shifts from collaborative problem-solving to quiet stalemate. None of this is the result of indifference. It reflects the limits of our conceptual frameworks. When we lack language for dysregulation, we default to the tools we know best.As our understanding of sensitized neural circuits has grown, so too has the realization that care does not have to depend on visible damage to be meaningful. When the pathology is one of regulation rather than structure, the goals shift subtly. The task is no longer to remove a lesion or suppress inflammation alone. It becomes, instead, to help the nervous system recalibrate.Education is often the first intervention. Naming central sensitization can reduce the threat associated with unexplained symptoms. When patients understand that amplification is a recognized physiologic process rather than a sign of fragility or fabrication, the nervous system can begin to soften its vigilance.Sleep, too, becomes central. So does physical movement, carefully planned and paced rather than forced. Psychological safety also matters: not because the pain is “psychological,” but because safety directly influences autonomic tone. In some cases, medications that modulate central neurotransmission are helpful. In others, hormonal stabilization, trauma-informed therapies, meditation or autonomic regulation strategies become part of the plan.None of these approaches are dramatic. They do not generate striking postoperative images or immediate radiologic proof of success. Their impact is often gradual, cumulative and relational. But they align with the mechanism.Nociplastic-centred care does not reject structural medicine. It simply recognizes that some forms of suffering originate within networks rather than tissues. And networks require a different kind of patience. Pain without a lesion still deserves precision. It deserves language. It deserves thoughtful intervention grounded in physiology rather than doubt.So even when the testing comes back normal. The pain continues to be abnormal. Between those two truths lies a widening understanding: that pathology does not always present as damage. Sometimes it reflects dysregulation; neural circuits shaped by injury, stress, or sustained vigilance. Medicine has long excelled at identifying what is broken. We are now learning to recognize what is amplified. The absence of a lesion does not diminish suffering; it challenges us to broaden our definition of disease to include the physiology of adaptation itself.Dr. Ginevra Mills is a reproductive endocrinologist and infertility specialist based in Victoria.

Pain without a lesion

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