Pain is subjective, by definition. No onecan truly experience the others’ pain. Though the need for objective markers ofpain is pressing to help develop more effective diagnosis and treatments, the currentstate-of-the-art pain evaluation method is still self-report by asking patients“how much pain do you feel now?”

Pain can be initiated by externalnociceptive input, but multiple factors can influence and modify painexperience, such as emotions, thoughts, beliefs and past memories, andtherefore complex interactions among multiple brain system (a.k.a., functionalconnectome*) are known to be important for pain. Chronic pain, which ruinseveryday life and causes tremendous socio-economic costs, is also known to be adisease of functional brain connectome. However, there has been no objectiveassessment of pain based on the functional brain connectome.

* Functional brain connectome: A map ofsystems-level functional interactions across multiple brain regions

A new study conducted by a research team ofSungkyunkwan University led by Choong-Wan Woo (Assistant professor, Departmentof Biomedical Engineering) developed a new neuroimaging biomarker of sustainedpain based on functional brain connectome in collaboration with Tor Wager(Professor, Department of Psychological and Brain Sciences) at Dartmouth College.The research team invented an effective and safe way to induce pain for a while(longer than 10 minutes) by applying capsaicin on participants’ tongue. Theyrecorded patterns of brain functional connectivity while participants wereexperiencing sustained pain using functional Magnetic Resonance Imaging (fMRI).The functional connectome-based biomarker not only succeeded to predictsubjective ratings of pain intensity across 109 participants, but it also predictedoverall severity of pain symptoms across 192 patients with clinical back pain.

“This study showed brain responses to experimentallyinduced sustained pain are quite similar to the brain activity patterns during clinicalpain”, said Professor Choong-Wan Woo, who is the corresponding author of thiswork. He added, “We believe this study provide new insight into understandingneural mechanisms of clinical pain, and ultimately can help many patientssuffering from chronic pain”, 

“Our results suggest that not only a set oflocal brain regions known to be related with pain but also the dynamic,functional interactions of whole brain are important for understanding theneural mechanisms of sustained pain” said Jae-Joong Lee, the first author ofthe study and a Ph.D. candidate in the Department of Biomedical Engineering,Sungkyunkwan University. He also added “This is a new evidence that pain is amulti-dimensional experience mediated by functional brain connectome.” 

This study was supported by Institute forBasic Science (IBS-R015-D1), National Research Foundation of Korea (2019R1C1C1004512),Ministry of Science and ICT, Korea (2019-0-01367-BabyMind), and Korean BrainResearch Institute (18-BR-03). The paper has published in Nature Medicine(Impact Factor 36.130) on Jan 4, Monday.

※ You can find its video abstract via thefollowing YouTube link: https://youtu.be/U_Y7vwGw5So

[Figure 1]

A functional connectome biomarkerpredictive of sustained pain intensity, named the Tonic Pain Signature (ToPS).Each line represents predictive weights of functional interactions between twodistinct brain regions in the biomarker model.

[Figure 2]

Selected connections of the functionalconnectome biomarker that are most import in prediction of sustained painintensity.