Medio-dorsal thalamic dysconnectivity in chronic knee pain: A possible mechanism for negative affect and pain comorbidity

Iwabuchi, Sarina J.; Drabek, Marianne M.; Cottam, William J.; Tadjibaev, Arman; Mohammadi-Nejad, Ali Reza; Sotiropoulos, Stamatios; Fernandes, Gwen S.; Valdes, Ana M.; Zhang, Weiya; Doherty, Michael; Walsh, David A.; Auer, Dorothee P.

Abstract

The reciprocal interaction between pain and negative affect is acknowledged but pain-related alterations in brain circuits involved in this interaction, such as the mediodorsal thalamus (MDThal), still require a better understanding. We sought to investigate the relationship between MDThal circuitry, negative affect and pain severity in chronic musculoskeletal pain. For these analyses, participants with chronic knee pain (CKP, n = 74) and without (n = 36) completed magnetic resonance imaging scans and questionnaires. Seed-based MDThal functional connectivity (FC) was compared between groups. Within CKP group, we assessed the interdependence of MDThal FC with negative affect. Finally, post hoc moderation analysis explored whether burden of pain influences affect-related MDThal FC. The CKP group showed altered MDThal FC to hippocampus, ventromedial prefrontal cortex and subgenual anterior cingulate. Furthermore, in CKP group, MDThal connectivity correlated significantly with negative affect in several brain regions, most notably the medial prefrontal cortex, and this association was stronger with increasing pain burden and absent in pain-free controls. In conclusion, we demonstrate mediodorsal thalamo-cortical dysconnectivity in chronic pain with areas linked to mood disorders and associations of MDThal FC with negative affect. Moreover, burden of pain seems to enhance affect sensitivity of MDThal FC. These findings suggest mediodorsal thalamic network changes as possible drivers of the detrimental interplay between chronic pain and negative affect.

Citation

Iwabuchi, S. J., Drabek, M. M., Cottam, W. J., Tadjibaev, A., Mohammadi-Nejad, A. R., Sotiropoulos, S., Fernandes, G. S., Valdes, A. M., Zhang, W., Doherty, M., Walsh, D. A., & Auer, D. P. (2022). Medio-dorsal thalamic dysconnectivity in chronic knee pain: A possible mechanism for negative affect and pain comorbidity. European Journal of Neuroscience, 57(2), 373-387. https://doi.org/10.1111/ejn.15880

• Journal Article Type: Article
• Acceptance Date: Oct 10, 2022
• Online Publication Date: Dec 1, 2022
• Publication Date: Dec 1, 2022
• Deposit Date: Feb 8, 2023
• Publicly Available Date: Feb 8, 2023
• Journal: European Journal of Neuroscience
• Print ISSN: 0953-816X
• Electronic ISSN: 1460-9568
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 57
• Issue: 2
• Pages: 373-387
• DOI: https://doi.org/10.1111/ejn.15880
• Keywords: General Neuroscience
• Public URL: https://nottingham-repository.worktribe.com/output/14322545
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/ejn.15880
• Additional Information: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.