Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

Ludovica Brusaferri; Zeynab Alshelh; Jack H. Schnieders; Angelica Sandström; Mehrbod Mohammadian; Erin J. Morrissey; Minhae Kim; Courtney A. Chane; Grace C. Grmek; Jennifer P. Murphy; Julia Bialobrzewski; Alexa DiPietro; Julie Klinke; Yi Zhang; Angel Torrado-Carvajal; Nathaniel Mercaldo; Oluwaseun Akeju; Ona Wu; Bruce R. Rosen; Vitaly Napadow; Nouchine Hadjikhani; Marco L. Loggia

doi:10.1016/j.bbi.2023.12.016

Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

Ludovica Brusaferri, Zeynab Alshelh, Jack H. Schnieders, Angelica Sandström, Mehrbod Mohammadian, Erin J. Morrissey, Minhae Kim, Courtney A. Chane, Grace C. Grmek, Jennifer P. Murphy, Julia Bialobrzewski, Alexa DiPietro, Julie Klinke, Yi Zhang, Angel Torrado-Carvajal, Nathaniel Mercaldo, Oluwaseun Akeju, Ona Wu, Bruce R. Rosen, Vitaly NapadowNouchine Hadjikhani, Marco L. Loggia

Research output: Contribution to journal › Article › peer-review

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Abstract

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [ ¹¹C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -V _T- and V _T ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [ ¹¹C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [ ¹¹C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.

Original language	English
Pages (from-to)	259-266
Number of pages	8
Journal	Brain, Behavior and Immunity
Volume	116
DOIs	https://doi.org/10.1016/j.bbi.2023.12.016 https://doi.org/10.1016/j.bbi.2023.12.016
Publication status	Published - 12 Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Keywords

Neuroinflammation; PET; MR; mental health; COVID-19; Pandemic; Chronic pain; Brain Age

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Brusaferri, L., Alshelh, Z., Schnieders, J. H., Sandström, A., Mohammadian, M., Morrissey, E. J., Kim, M., Chane, C. A., Grmek, G. C., Murphy, J. P., Bialobrzewski, J., DiPietro, A., Klinke, J., Zhang, Y., Torrado-Carvajal, A., Mercaldo, N., Akeju, O., Wu, O., Rosen, B. R., ... Loggia, M. L. (2023). Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset. Brain, Behavior and Immunity, 116, 259-266. https://doi.org/10.1016/j.bbi.2023.12.016, https://doi.org/10.1016/j.bbi.2023.12.016

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title = "Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset",

abstract = "The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 {\textquoteleft}Pre-Pandemic{\textquoteright}, 28 {\textquoteleft}Pandemic{\textquoteright}) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [ 11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 ({\textquoteleft}Pre-Pandemic{\textquoteright} cLBP) or between August 2020 and May 2022 ({\textquoteleft}Pandemic{\textquoteright} cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -V T- and V T ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [ 11C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [ 11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.",

keywords = "Neuroinflammation; PET; MR; mental health; COVID-19; Pandemic; Chronic pain; Brain Age",

author = "Ludovica Brusaferri and Zeynab Alshelh and Schnieders, {Jack H.} and Angelica Sandstr{\"o}m and Mehrbod Mohammadian and Morrissey, {Erin J.} and Minhae Kim and Chane, {Courtney A.} and Grmek, {Grace C.} and Murphy, {Jennifer P.} and Julia Bialobrzewski and Alexa DiPietro and Julie Klinke and Yi Zhang and Angel Torrado-Carvajal and Nathaniel Mercaldo and Oluwaseun Akeju and Ona Wu and Rosen, {Bruce R.} and Vitaly Napadow and Nouchine Hadjikhani and Loggia, {Marco L.}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = dec,

day = "12",

doi = "10.1016/j.bbi.2023.12.016",

language = "English",

volume = "116",

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Brusaferri, L, Alshelh, Z, Schnieders, JH, Sandström, A, Mohammadian, M, Morrissey, EJ, Kim, M, Chane, CA, Grmek, GC, Murphy, JP, Bialobrzewski, J, DiPietro, A, Klinke, J, Zhang, Y, Torrado-Carvajal, A, Mercaldo, N, Akeju, O, Wu, O, Rosen, BR, Napadow, V, Hadjikhani, N & Loggia, ML 2023, 'Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset', Brain, Behavior and Immunity, vol. 116, pp. 259-266. https://doi.org/10.1016/j.bbi.2023.12.016, https://doi.org/10.1016/j.bbi.2023.12.016

TY - JOUR

T1 - Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

AU - Brusaferri, Ludovica

AU - Alshelh, Zeynab

AU - Schnieders, Jack H.

AU - Sandström, Angelica

AU - Mohammadian, Mehrbod

AU - Morrissey, Erin J.

AU - Kim, Minhae

AU - Chane, Courtney A.

AU - Grmek, Grace C.

AU - Murphy, Jennifer P.

AU - Bialobrzewski, Julia

AU - DiPietro, Alexa

AU - Klinke, Julie

AU - Zhang, Yi

AU - Torrado-Carvajal, Angel

AU - Mercaldo, Nathaniel

AU - Akeju, Oluwaseun

AU - Wu, Ona

AU - Rosen, Bruce R.

AU - Napadow, Vitaly

AU - Hadjikhani, Nouchine

AU - Loggia, Marco L.

PY - 2023/12/12

Y1 - 2023/12/12

N2 - The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [ 11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -V T- and V T ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [ 11C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [ 11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.

AB - The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [ 11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -V T- and V T ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [ 11C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [ 11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.

KW - Neuroinflammation; PET; MR; mental health; COVID-19; Pandemic; Chronic pain; Brain Age

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U2 - 10.1016/j.bbi.2023.12.016

DO - 10.1016/j.bbi.2023.12.016

M3 - Article

SN - 1090-2139

VL - 116

SP - 259

EP - 266

JO - Brain, Behavior and Immunity

JF - Brain, Behavior and Immunity

ER -

Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

Abstract

Bibliographical note

Keywords

UN SDGs

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