University of Essex scientists analysed brain scans from more than 2,000 people and found recurring differences in regions involved in processing pain and its emotional impact.
The major review covered 48 studies involving people with migraine, fibromyalgia, irritable bowel syndrome, and chronic lower back pain, alongside pain-free volunteers.
On average, people living with chronic primary pain consistently rated controlled painful stimuli as more intense than healthy participants.
Researchers also found that activation was reported most consistently across studies in key parts of the brain, particularly the insula and cingulate cortex, which are involved in how pain is detected, interpreted, and experienced.
'More pain'
Lead researcher Dr Elia Valentini, from the Department of Psychology, said: "Across these studies patients and pain-free volunteers received the same controlled stimulus, yet patients reported more pain.
"What's striking is that across very different conditions, migraine, fibromyalgia, and IBS, the same core network of brain regions responds to painful stimulation.
"But in people with chronic primary pain, the anterior insula, an area that helps flag threat and bodily salience, tends to respond more strongly than it does in pain-free volunteers.
"This finding dovetails well fits with other research published this year, which found that in chronic primary pain, how strongly the anterior insula connects with the brain's stress-processing networks tracks patients' cortisol levels and perceived stress, more evidence that this region sits at the crossroads of pain and stress."
The findings may help explain why people with chronic pain can experience greater pain even when the physical stimulus is like that given to someone without chronic pain.
The analysis drew together data from 1,206 patients and 846 control subjects exposed to painful stimuli including heat, pressure, electrical stimulation, and visceral pain while undergoing brain imaging.
Chronic pain
Patients showed particularly consistent activity in the dorsal anterior insula and areas of the cingulate cortex, both repeatedly linked to pain processing.
But the researchers also uncovered an important complication.
There was no single, reliable brain pattern that consistently separated chronic pain patients from healthy people when groups were directly compared.
That means brain scans are not yet ready to provide a simple diagnostic test for chronic pain.
The team says major differences in study design, patient groups and pain-testing methods are likely masking clearer biological signals and are calling for more standardised research.
'Building evidence'
Dr Valentini, added: "What we didn't find is just as important as what we did.
"No single brain signature reliably told patients and healthy volunteers apart, and it isn't because lack of data. Studies differ so much in whom they recruit, how they stimulate and how they analyse that any real signal is probably being washed out.
"What we need, more generally across fields, is a generation of studies designed to be combined: the same paradigms, the same reporting standards, and both within- and between-subject comparisons run properly.
"Once the field moves to more harmonised methods, we'll be in a much better position to know whether these regions can genuinely serve as a marker for chronic primary pain.
"Importantly, this isn't about replacing clinical judgement with a brain scan but it's about building the evidence carefully enough that imaging could one day help tailor treatment to the individual."
The researchers say more reliable brain signatures could eventually improve diagnosis, and help doctors tailor treatments more precisely, including psychological therapies and targeted brain stimulation.
The study used the World Health Organization’s ICD-11 chronic primary pain framework, which includes conditions such as fibromyalgia, migraine, chronic lower back pain, and irritable bowel syndrome.
The research, by Dr Khetam Al-Faraj, Dr Paul Hanel and Dr Elia Valentini, is published in The Journal of Pain.
