Background & Aims
The neural mechanisms underlying the persistence of pain after a technically successful arthroplasty in osteoarthritis (OA) have received limited attention, and there is a dearth of direct evidence examining the brain’s role as a predisposing factor for chronic pain in this context. Additionally, while psychological factors such as pain catastrophizing, anxiety, and depression, as well as clinical factors like pain intensity and neuropathic pain, have been linked to the sustained presence of pain in the disease, their association with brain properties remains underexplored.
Our objective is to investigate the correlation between subcortical brain anatomical and functional properties and clinical characteristics of osteoarthritis pain, with a focus on predicting persistent pain after total knee replacement.
Methods
Patients with knee osteoarthritis (n = 81) awaiting total arthroplasty underwent pre-surgery clinical, psychological assessment, and brain magnetic resonance imaging. The brain MRI utilized a T1 sequence for anatomical assessment, and subcortical brain indices (volume and shape) were derived using FIRST, FSL, FMRIB. A mixed-design ANCOVA analyzed the interplay between subcortical anatomical volumes and surgical pain outcomes (pain levels at 6 months post-surgery; <3 OA recovery; >= 3 OA persistence). Vertex-wise statistics identified shape distinctions between groups. Multiple clinical/psychological indices were compared using FRD corrected T-statistics. Sequential regression models assessed the redundancy of clinical predictors and subcortical brain biomarkers in explaining post-surgical pain, treating it as a continuous variable and controlling for baseline pain. Each model incorporated an additional block of variables.
Results
We establish that distinct pre-surgical subcortical volumes (SCv) are associated with post-surgery pain outcomes (SCv x OA recovery/persistency F(5.45) = 2.26, p = 0.043). Post-hoc analysis reveals that differences in bilateral amygdala, thalamus, and left hippocampus volumes contribute to these distinctions—larger volumes in all structures indicate persistent pain (p < 0.05). Additionally, altered shape in the right anterior hippocampus and right amygdala is associated with pain persistence six months after surgery (p < 0.001). Longer pain duration, elevated pre-surgical anxiety levels, and the neuropathic character of pain predict post-surgical pain outcomes (p < 0.01, FDR corrected).
Our sequential hierarchical models demonstrate that the predictive value of subcortical anatomical indices for post-surgical pain is additive to clinical predictors, revealing singular influences (R2 change of 0.17, p < 0.01; final model R2 = 0.455, p < 0.01).
Conclusions
Current perspectives on persistent pain after a technically successful total knee replacement (TKR) surgery have primarily focused on peripheral and spinal cord sensitization, abnormal descending pain modulation, or clinical/psychological dimensions, lacking a clear mechanistic link to pain physiology. Our findings reveal that structural properties of the brain’s limbic circuitry, especially the amygdala, hippocampus, and thalamus, are linked to pain persistence after TKR surgery. These results emphasize the significance of limbic neuroanatomical factors in chronic pain persistence, providing new avenues for studying post-surgery pain mechanisms.
Importantly, in our sample, we confirm that anxiety and the neuropathic pain profile are associated with negative post-surgical outcomes. However, they act as independent predictors, highlighting the need for a more comprehensive understanding and mapping of brain/clinical outcomes.
References
Barroso J, Branco P, Pinto-Ramos J, Vigotsky AD, Reis AM, Schnitzer TJ, Galhardo V, Apkarian AV. Subcortical brain anatomy as a potential biomarker of persistent pain after total knee replacement in osteoarthritis. Pain. 2023 Oct 1;164(10):2306-2315. doi: 10.1097/j.pain.0000000000002932. Epub 2023 Jul 13. PMID: 37463229.
Presenting Author
Joana Barroso
Poster Authors
Joana De Brito Barroso Monteiro
MD, PhD
Northwestern University
Lead Author
Topics
- Specific Pain Conditions/Pain in Specific Populations: Rheumatology, Arthritis, and Other