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The neuroinflammatory component of negative affect in patients with chronic pain

Molecular Psychiatry volume 26, pages 864–874 (2021)Cite this article

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Abstract

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18 kDa translocator protein (TSPO), and changes in functional connectivity. 25 cLBP patients (42.4 ± 13 years old; 13F, 12M) with chronic low back pain (cLBP) and 27 healthy control subjects (48.9 ± 13 years old; 14F, 13M) received an integrated (i.e., simultaneous) positron emission tomography (PET)/magnetic resonance imaging (MRI) brain scan with the second-generation TSPO ligand [11C]PBR28. The relationship between [11C]PBR28 signal and NA was assessed first with regression analyses against Beck Depression Inventory (BDI) scores in patients, and then by comparing cLBP patients with little-to-no, or mild-to-moderate depression against healthy controls. Further, the relationship between PET signal, BDI and frontolimbic functional connectivity was evaluated in patients with mediation models. PET signal was positively associated with BDI scores in patients, and significantly elevated in patients with mild-to-moderate (but not low) depression compared with controls, in anterior middle and pregenual anterior cingulate cortices (aMCC, pgACC). In the pgACC, PET signal was also associated with this region’s functional connectivity to the dorsolateral PFC (pgACC-dlPFC), and mediated of the association between pgACC-dlPFC connectivity and BDI. These observations support a role for glial activation in pain-comorbid NA, identifying in neuroinflammation a potential therapeutic target for this condition.

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Acknowledgements

The authors would like to thank Grae Arabasz, Shiley Hsu, Regan Butterfield, Judit Sore, Patricia McCarthy, Marlene Wentworth, Amy Kendall, and Natacha Nortelus for help with data collection. They would like to thank Dr. Marc O. Martel for helpful discussions. The study was supported by the following funding sources: 1R21NS087472-01A1 (MLL), 1R01NS095937-01A1 (MLL), DoD-W81XWH-14-1-0543 (MLL), and 1R01NS094306-01A1 (MLL), Harvard Catalyst Advance Imaging Pilot Grant (JMH), 5T32EB13180 (T32 supporting DSA), P41RR14075, and P41EB015896.

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  1. A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School (MGH/HMS), Boston, MA, USA

    D. S. Albrecht, M. Kim, A. Torrado-Carvajal, C. Bergan, E. Protsenko, A. Kucyi, J. M. Hooker, V. Napadow & M. L. Loggia

  2. Department of Anesthesia, Critical Care and Pain Medicine, MGH/HMS, Boston, MA, USA

    O. Akeju & Y. Zhang

  3. Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, HMS, Boston, MA, USA

    R. R. Edwards & V. Napadow

  4. Department of Neurology, Stanford University Medical Center, Stanford, CA, USA

    A. Kucyi

  5. Departments of Anesthesiology and Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    A. D. Wasan

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  1. D. S. Albrecht
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Albrecht, D.S., Kim, M., Akeju, O. et al. The neuroinflammatory component of negative affect in patients with chronic pain. Mol Psychiatry 26, 864–874 (2021). https://doi.org/10.1038/s41380-019-0433-1

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