An editorial in Nature Neuroscience argued that biological tests, such as brain scans and biomarkers, do not prove or disprove a person’s pain. However, a responding researcher said that doesn’t make biomarkers “futile or conceptually flawed.”
Lead pain researcher Jan Vollert at the University of Exeter and 10 colleagues argued that the complex biopsychosocial nature of pain makes measuring biomarkers “tricky and nonspecific.” They wrote that the same brain activity can mean very different experiences for different people under certain situations. A 5 on a scale of 0 to 10 (where 0 is no pain and 10 is excruciating pain) for a person could be someone’s 10 or 2.
Vollert et al. gave an example with mindfulness meditation, where pain relief achieved through meditation doesn’t produce a single, clean brain signature. Instead, they wrote that brain scans may show an expected decrease in sensory activation but also increased activity in brain regions associated with pain.
Likewise, unpleasant emotional experiences that have nothing to do with physical injury, such as social exclusion, can activate some of the same neural processes as physical pain but in different activation patterns.
“Any diagnostic biomarker of pain would have to be validated against people’s private inner experiences, which can never guarantee it accurately reflects someone else’s,” Vollert et al. wrote.
Instead of biomarkers, Vollert et al. proposed that patients’ self-report should be the gold standard. They wrote that it is understandable that patients want “objective” pain biomarkers, who may feel pressure to “prove” their pain to clinicians.
In fact, a 2022 study of more than 5,800 people in England found people in pain experience more perceived discrimination than those without pain — with “greater depressive symptoms and loneliness over 6-year follow-up.” These people were more likely to be:
- Older
- Female
- Less wealthy
- Non-white
- Not married
- A smoker
- Sedentary
- Overweight
“However…imperfect biomarkers of pain would be likely to worsen the problem rather than solve it, as they would be given precedence over self-reports when the two conflicted,” Vollert et al. wrote. “Some people might be validated as their pain was made visible, but many others would be told that their pain was not real because it did not show up on a medical scan.”
The response
Dr. Choong-Wan Woo, an associate professor in neuroscience at Sungkyunkwan University in Suwon, South Korea, wrote that biomarkers should be understood as “partial, imperfect and necessarily incomplete models that might still be useful in some contexts.”
Using statistician George Box’s aphorism, “all models are wrong, but some are useful,” Woo wrote that pain is too complex, individualistic, and context-dependent to have a model that accurately reflects anyone’s lived experience. Any model created “necessarily involves” abstraction, reduction, and systematic bias, he wrote.
In his example of a clinical drug-development trial, self-report is vulnerable to the power of expectation and context (commonly associated with the placebo effect), and high reliance on self-report may contribute to high failure rates. Supplementary biological measures, Woo suggested, could help researchers distinguish genuine drug effects from non-specific responses.
“The appropriate question, then, is not whether pain can be reduced to biological measures — it cannot — but how much additional, context-sensitive information bio-markers can provide, and in which settings,” Woo wrote.
As imperfect as biomarker evidence is, Woo suggested that such measurements should be approached with “epistemic humility and ethical clarity.”
“Addressing them requires far broader efforts, including shifts in social norms, reforms in education and training, and changes in health policy that more deeply reflect an integrated bio-psycho-social perspective of pain,” he wrote.
The brain scan that went to court
Vollert et al. cited a 2005 legal trial in Tucson, Arizona, where a truck driver Carl Koch was burned with molten asphalt when a hose connection broke loose. Koch was still in pain a year later, and sued his former employer Western Emulsions.
Koch had his brain scanned by Joy Hirsch, a neuroscientist who was then running the fMRI Research Center at Columbia University in New York City who had developed a method she said could “tap into” chronic pain, according to a Harvard press release. Hirsch claimed that different patterns of brain activity were triggered by stimulation of Koch’s injured right arm compared to his unaffected left arm and submitted her findings as evidence.
The judge deemed the fMRI test admissible even though it was conducted by a neuroscientist with no experience in the pain field. The case was settled for $800,000 — more than 10 times the Western Emulsions’ initial offering, according to Koch’s lawyer Roger Strassburg.
Vollert told Massage & Fitness Journal in an online interview that a judicial system will always look for objective proof, but that proof does not exist when it comes to pain.
“Even when it looks like there is objective proof – say, a scar or visible injury – this does not tell us if or how much pain there is,” he said. “I think having the humility to understand that is important. The best they can do is to hear expert testimony on how plausible a case is. That won’t free them from deciding on a case-by-case basis.”
Neuroscientist Karen Davis of the University of Toronto wrote in Pain Reports that using an fMRI test is like using a lie detector test, implying that the patient is dishonest about the pain experience. She identified flaws in how the fMRI evidence was handled:
- Examined evoked pain rather than the ongoing chronic pain Koch claimed to suffer
- Lacked any evidence to link Koch’s chronic pain with any specific brain response
- Lacked control conditions to rule out nonspecific brain activations
- Lacked countermeasures for deception
- Provided no evidence that the data analysis met standards of statistical rigor, was repeatable or robust, or represented an abnormal response compared with healthy individuals
Davis added that fMRI is expensive and largely unavailable outside major cities, and many patients cannot undergo fMRI at all, such as those with pacemakers, those who are pregnant, or those with severe claustrophobia..
“Privacy of data pertaining to brain structure and function is another issue that must be carefully examined if brain imaging is to be acquired for the purposes of pain diagnosis,” she wrote.
Vollert said he and his colleagues first wrote the editorial in 2023 after they read a paper by Shirvalkar et al. that implied chronic pain can be predicted, which they disagreed.
“[Healthcare professionals] should accept what the patient is saying, and be aware that most pain is invisible,” Vollert said. “[With] so many people living with chronic pain [facing] disbelief from medical professionals, hearing someone say that they understand that the pain is real can help a lot.”
Vollert said he thinks it is best for the general public — especially those with loved ones with chronic pain — to understand that pain is invisible.
“Do believe them. If others do not, point them to our work to show them that just because you can’t see the pain, that doesn’t mean it isn’t there,” he said.
Further reading
Weight discrimination linked to chronic pain
When fear isn’t the main driver: Rethinking about psychological models of chronic pain
Perceived discrimination risk of chronic pain, more so if you’re older
Nick Ng, BA
Nick Ng is the editor of Massage & Fitness Jounal and the managing editor for My Neighborhood News Group.
An alumni from San Diego State University with a bachelor’s degree in graphic communications, Nick had also completed his massage therapy training at International Professional School of Bodywork in San Diego in 2014. In 2021, he earned an associate’s degree in journalism at Palomar College.
When he gets a chance, he enjoys weightlifting at the gym, salsa dancing, and exploring new areas in the Puget Sound area in Washington state.
