703: Changes in ongoing regional brain activity and connectivity in Persistent Spinal Pain Syndrome

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Pain Category (ICD-11), Chronic postsurgical pain, Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Persistent Spinal Pain Syndrome (PSPS) describes chronic pain in the lower back or leg that is either present without prior spinal surgery (PSPS-Type 1) or following spinal surgery (PSPS-Type 2) (van de Minkelis et al., 2024). The mechanisms underpinning PSPS-T2 are complex and the specifics regarding on-going activity levels and patterns of neural activity in PSPS-T2 remain unclear. Thus, this study aimed to define regional cerebral blood flow and resting state functional connectivity in individuals with PSPS-T2 using arterial spin labelling (ASL), and resting state functional magnetic resonance imaging (fMRI), respectively.

Methods: 20 PSPS-T2 participants (13 males) and 40 pain-free age and sex matched controls (26 males) were recruited. All PSPS participants met diagnostic criteria for PSPS-T2. During 3-Tesla MRI scanning sessions, participants underwent anatomical, ASL, and fMRI scans. ASL and fMRI scans were processed using standard analysis pipelines in SPM12 and signal changes during the fMRI scan were determined using a repeated box car model (p<0.001 uncorrected, 5 contiguous voxels). To identify changes in resting cerebral blood flow (CBF) a second-level random-effects analysis with age and sex added as nuisance variables was conducted (p<0.001 uncorrected, 5 contiguous voxels).

Results: Compared to pain-free controls, PSPS-T2 participants demonstrated significantly increased CBF in the midbrain periaqueductal grey matter (PAG), dorsal pons and cerebellar vermis and decreased CBF in insula. Using the PAG cluster as a seed for the resting state functional connectivity analysis, PSPS-T2 showed increased functional connectivity with the medial prefrontal cortex, putamen, left primary somatosensory and motor cortex and decreased functional connectivity with the cerebellum, anterior cingulate cortex, and orbitofrontal cortex when compared to controls. Moreover, regional CBF was positively correlated with pain intensity in the nucleus accumbens (NAc) only.

Conclusions: Our findings demonstrate PSPS-T2 as being characterised by ongoing changes in neural activity as assessed by regional cerebral blood flow within pain modulatory brain systems comprising the PAG and NAc rather than pain sensory regions like thalamic subnuclei or the somatosensory cortices. These results suggest that PSPS-T2 may further be associated with altered pain modulatory ability, a hallmark of several chronic pain states which leverage this circuitry function. By improving the functional neurobiological understanding of brain systems in treatment-resistance chronic pain conditions such as PSPS-T2, we hope to inform the development of more efficacious and targeted treatments.

References: van de Minkelis, J., Peene, L., Cohen, S. P., Staats, P., Al-Kaisy, A., Van Boxem, K., . . . Van Zundert, J. (2024). 6. Persistent spinal pain syndrome type 2. Pain Practice, 24(7), 919-936. doi:https://doi.org/10.1111/papr.13379

Presenting Author: Allan Peng
Submitting Author: Allan Peng

Senior Author: Luke A. Henderson

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Rebecca V. Robertson: PhD - The University of Sydney
• Ramesh Heidary: MDataSci - The University of Sydney
• Jenny Sun: BSc - The University of Sydney
• Lewis S. Crawford: PhD - The University of Sydney
• Noemi Meylakh: PhD - The University of Sydney
• Kevin A. Keay: PhD - The University of Sydney
• Chris C. Peck: PhD - The University of Sydney, National University of Singapore
• Alister Ramachandran: MBBS - The University of Sydney
• Luke A. Henderson: PhD - The University of Sydney