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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.


Sarina J. Iwabuchi

Marianne M. Drabek

William J. Cottam

Arman Tadjibaev

Gwen S. Fernandes

Michael Doherty

Professor of Rheumatology


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.


Iwabuchi, S. J., Drabek, M. M., Cottam, W. J., Tadjibaev, A., Mohammadi-Nejad, A. R., Sotiropoulos, S., …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.

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
Keywords General Neuroscience
Public URL
Publisher URL
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.


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