389: From Periphery to Brain: The Relation of Sensitization and Resting-State Functional Connectivity

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, Quantitative Sensory testing (static and dynamic, e.g., HPT, PPT, CPM, TSP, offset analgesia), Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Sensitization on peripheral, spinal and supraspinal levels ought to be reflected in different proxy measures. Hypersensitivity in the patient's most painful region (MP) likely indicates peripheral sensitization and hypersensitivity in a pain-free, adjacent area (AD) spinal sensitization. Hypersensitivity in a remote, pain-free site (CON) or pain catastrophizing (PCS), conceivably involves supraspinal circuits [1,4,5]. While supraspinal sensitization is associated with resting-state functional connectivity (rsFC) [3], it remains unclear if such a relation exists for peripheral or spinal sensitization. This study investigated relations between indicators of peripheral, spinal and supraspinal sensitization, respectively, and rsFC in chronic low back pain (cLBP) patients.

Methods: Forty-five cLBP patients underwent 12min resting-state fMRI (3T, whole-brain, TR:846ms, TE: 30ms, 2.2mm isotropic voxels), quantitative sensory testing in MP, AD and CON, and questionnaires. MRI data was preprocessed (motion and distortion correction, resampling to MNI152 space, high-pass filtering, smoothing and ICA-based denoising) and analyzed using ICA and dual regression in FSL [2]. Peripheral, spinal and supraspinal measures that differed in patients compared to age- and sex-matched healthy controls (specifically mechanical pain sensitivity in MP, AD and CON, pressure sensitivity in CON, and PCS) were assessed for correlation with rsFC using permutation tests (5000 permutations, threshold-free-cluster-enhanced family-wise-error rate correction).

Results: Higher mechanical pain sensitivity and higher pressure sensitivity in CON correlated with lower rsFC of the middle occipital gyrus and lower rsFC of the anterior insula to the default mode network, respectively. In addition, higher PCS scores correlated with higher rsFC within the sensorimotor network. No associations of mechanical pain sensitivity in AD and MP with rsFC were found.

Conclusions: PCS and hypersensitivity in CON, but not in AD or MP, correlated with rsFC, indicating that supraspinal but not spinal or peripheral sensitization is related to rsFC. Importantly, involved networks were previously linked to supraspinal sensitization [3]. Notably, hypersensitivity and pain catastrophizing were associated with different networks, suggesting that, although both have been linked to supraspinal sensitization, they may still involve distinct mechanisms. In conclusion, these findings suggest that rsFC is specifically related to sensitization processes at a supraspinal level and highlight the importance of distinguishing central sensitization in spinal and supraspinal components.

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[4] Sirucek, L., De Schoenmacker, I., Scheuren, P. S., Lütolf, R., Gorrell, L. M., Langenfeld, A., Baechler, M., Rosner, J., Wirth, B., Hubli, M., & Schweinhardt, P. (2024). Indication for spinal sensitization in chronic low back pain: mechanical hyperalgesia adjacent to but not within the most painful body area. Pain reports, 9(4), e1166. https://doi.org/10.1097/PR9.0000000000001166

[5] Taub, C. J., Sturgeon, J. A., Johnson, K. A., Mackey, S. C., & Darnall, B. D. (2017). Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study. Pain research & management, 2017, 7892494. https://doi.org/10.1155/2017/7892494

Presenting Author: Madeleine Hau
Submitting Author: Madeleine Hau

Senior Author: Petra Schweinhardt

IASP 2026 Global Year theme of Neuropathic Pain: No

• Laura Sirucek: PhD - Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
• Christian Beckman: PhD - Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
• Petra Schweinhardt: PhD, M Chiro Med - Department of Chiropractic Medicine, Integrative Spinal Research Group, Balgrist University Hospital, University of Zurich, Zurich, Switzerland