The interplay of body and mind in relation to pain biomarkers
- Michele Curatolo
- Sep 2
- 3 min read
I have written about the sense and nonsense of biomarkers for pain in a previous blog post. Here is a summary:
The term "biomarker for pain" is frequently misused and illogical; pain is defined by personal experience and not by an "objective" measure.
Key points about biomarkers include that they must be measurable and serve specific purposes (e.g., diagnostic, prognostic, predictive, see diagram below). Determining the presence or absence of pain is not a meaningful purpose of a biomarker.
A measure cannot be used as a biomarker unless it meets specific validation criteria; essential questions for biomarker validation involve:
Is the strength of association of a biomarker with pain relief or other patient-relevant outcomes sufficient to support its use?
What are the risks of false positives or negatives?
Do the benefits of using the biomarker outweigh the costs?
If you want to know more, read the whole blog here.
Here, I address the interesting perspective of enhancing the usefulness of biomarkers by combining biological and psychosocial measures, as demonstrated by a recent and relevant study (Fillingim et al. Biological markers and psychosocial factors predict chronic pain conditions. Nat Hum Behav. 2025).
What did the researchers do?
The study concentrated on biomarkers, but instead of solely focusing on biological markers, such as brain and bone imaging, blood immunoassays, and genetic information, the researchers took a more comprehensive approach by also considering psychosocial factors. They included aspects such as mood, stress levels, and past psychological trauma, which can significantly impact a person's pain experience (read more here). Utilizing data from the UK Biobank, the researchers employed machine learning techniques to associate biological and psychosocial factors with painful medical conditions (for example, rheumatoid arthritis) or self-reported chronic pain (for example, back pain).
What did they find?
Biological biomarkers alone were associated with painful medical conditions, but not with self-reported pain. Adding psychosocial measures to the biological markers strengthened the association with chronic pain conditions. In addition, the association with self-reported pain, which was lacking with biological measures alone, became significant when the psychosocial factors were considered. Therefore, placing the biological markers within the context of individual emotional and social circumstances improved their association with chronic pain.
What does this mean for us?
It confirms the validity of the biopsychosocial approach to pain that recognizes the interconnectedness of biological and psychosocial factors in determining how individuals ultimately experience pain. Once again, this research encourages healthcare professionals to adopt an integrated perspective on pain, a shift from seeing pain as the result of purely biological processes to understanding it as a complex interplay between multiple factors. Accordingly, this interplay needs to be explained to patients (read more here on why and how to communicate this information).
For research, the findings support our approach to studying the molecular mechanisms of human pain by including measures of psychosocial functioning. Read here how our group is trying to understand the mechanisms of pain in a holistic way .
But how useful can such a large set of multiple measures be in clinical reality?
Measures can be time-consuming and expensive. Some of them are invasive. Two essential questions arise:
Is performing a large battery of tests, involving imaging, blood tests, lengthy questionnaires, and other measures, sustainable and affordable?
If so, does using them or not make a difference in terms of the patient's pain?
These are crucial questions for future studies on the feasibility and clinical usefulness of biomarkers, a research that is still largely lacking.