Neuroimaging Correlates of Post-Stroke Pain After Ischemic Stroke: Secondary Analysis of the INSPiRE-TMS Trial.

Background: Post-stroke pain (PSP) affects nearly half of stroke survivors, severely compromising quality of life. The causes of PSP remain underexplored, although there is likely a complex interplay of lesion effects, psychological factors and mobility that play a role in the development of PSP. The aim of the study was to investigate clinical characteristics associated with PSP, as well as structural and functional correlates of PSP using lesion symptom (LSM) and network mapping (LNM).

Methods: We analyzed data from the INSPiRE-TMS cohort, encompassing 1,022 minor ischemic stroke patients. Pain severity and psychological factors (EQ5D-3L questionnaire) were assessed annually for up to 3 years. In a sub-group of 391 patients with available imaging data, LSM and LNM analyses were conducted to identify neural correlates of PSP.

Results: Overall, 47% of patients reported pain 1-year post-stroke. Multivariable regression analyses identified baseline anxiety as being associated with PSP assessed at 1-year post-stroke (OR 2.90, 95% CI 1.17-7.17, p=0.021). LSM did not identify any voxels associated with new severe pain. LNM identified a network involving anterior cingulate cortex, thalamus and insular cortex. Adjusting for anxiety highlighted distinct network contributions, suggesting interactive effects of psychological states on pain perception. Automated comparison to large metanalytical findings using Neurosynth associated the terms 'pain' and 'nociception' most strongly to the identified network.

Conclusion: PSP is closely associated with psychological factors such as anxiety. LNM of PSP revealed disruptions in a pain-related neural network consistent with prior pain research. These results warrant external validation and could guide future network-targeted neuromodulation therapies.

Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01586702 .