Background & Aims
Complex regional pain syndrome (CRPS) is a debilitating condition characterized by chronic pain, allodynia, and vasomotor changes. While recent brain imaging studies highlight the role of the limbic system in pain chronification, little has been published on cerebral processes related to the transition from acute to chronic CRPS. We aim to test whether existing markers of pain chronification are also observed in CRPS, explore for further changes in brain connectivity, and create possible links to its core clinical features.
Methods
An observational cohort study of clinical CRPS patients with no history of brain injury recruited as part of a larger clinical research group on multiple chronic pain conditions (KFO5001). Functional brain imaging (fMRI) and quantitative sensory testing data were analyzed in this work. We studied power spectral density of low-frequency fluctuations and functional connectivity of resting brain BOLD activity in regions related to pain and pain chronification.
Results
We compared 41 patients allocated to groups of 22 acute (aCRPS, 14 females) and 19 chronic CRPS (cCRPS, 13 females) based on disease duration at the time of the fMRI (aCRPS?12 months vs. cCRPS>12 months). The power of the slow-5 low-frequency band (0.01-0.027Hz) in nucleus accumbens accurately classified acute from chronic CRPS patients with an AUC > 0.7. Functional connectivity (fc) between nucleus accumbens and cortex was increased in cCRPS patients. Exploratory analyses showed increased fc within the default mode network and disconnection from the salience network in cCRPS. Furthermore, the putamen showed increased fc with secondary motor areas and reduced power in the slow-5 frequency band. Corticostriatal connectivity scaled positively with higher pressure pain threshold measured obtained using quantitative sensory testing.
Conclusions
Functional brain imaging not only corroborates the convergence of parameters indicating pain chronification, but also hints towards the role of major resting-state networks and the putamen in the transition from acute to chronic CRPS. This complements and challenges existing perspectives on fMRI in chronic pain which – so far – mainly focuses on comparing with healthy controls. We also establish links between cerebral fMRI and prominent clinical features of CRPS, potentially bridging the gap between central and peripheral phenotypes.
References
Makary MM, Polosecki P, Cecchi GA, et al. Loss of nucleus accumbens low-frequency fluctuations is a signature of chronic pain. Proc Natl Acad Sci U S A 2020; 117(18): 10015-23.
Presenting Author
Paul Geha
Poster Authors
Paul Geha
MD
University of Rochester
Lead Author
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)