The neuroinflammatory component of negative affect in patients with chronic pain
- PMID: 31138890
- PMCID: PMC7001732
- DOI: 10.1038/s41380-019-0433-1
The neuroinflammatory component of negative affect in patients with chronic pain
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.
Conflict of interest statement
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
Figures
Similar articles
-
Neuroimmune signatures in chronic low back pain subtypes.Brain. 2022 Apr 29;145(3):1098-1110. doi: 10.1093/brain/awab336. Brain. 2022. PMID: 34528069 Free PMC article.
-
Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation.Brain Behav Immun. 2019 Jan;75:72-83. doi: 10.1016/j.bbi.2018.09.018. Epub 2018 Sep 14. Brain Behav Immun. 2019. PMID: 30223011 Free PMC article.
-
Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset.Brain Behav Immun. 2024 Feb;116:259-266. doi: 10.1016/j.bbi.2023.12.016. Epub 2023 Dec 9. Brain Behav Immun. 2024. PMID: 38081435
-
Acetamidobenzoxazolone scaffold as a promising translocator protein (18 kDa, TSPO) marker for neuroinflammation imaging: Advancement in last decennial period.Drug Dev Res. 2022 Nov;83(7):1519-1533. doi: 10.1002/ddr.21989. Epub 2022 Sep 8. Drug Dev Res. 2022. PMID: 36074736 Review.
-
Neurochemical changes in patients with chronic low back pain detected by proton magnetic resonance spectroscopy: A systematic review.Neuroimage Clin. 2016 Nov 24;13:33-38. doi: 10.1016/j.nicl.2016.11.006. eCollection 2017. Neuroimage Clin. 2016. PMID: 27920977 Free PMC article. Review.
Cited by
-
Global Trends and Hotspots on Microglia Associated with Pain from 2002 to 2022: A Bibliometric Analysis.J Pain Res. 2023 Aug 15;16:2817-2834. doi: 10.2147/JPR.S413028. eCollection 2023. J Pain Res. 2023. PMID: 37600079 Free PMC article.
-
Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures.Brain Behav Immun. 2024 Jul;119:713-723. doi: 10.1016/j.bbi.2024.04.015. Epub 2024 Apr 18. Brain Behav Immun. 2024. PMID: 38642615 Free PMC article.
-
Motilin and its receptor are expressed in the dorsal horn in a rat model of acute incisional pain: Intrathecal motilin injection alleviates pain behaviors.Front Neurosci. 2023 Feb 2;17:1104862. doi: 10.3389/fnins.2023.1104862. eCollection 2023. Front Neurosci. 2023. PMID: 36816129 Free PMC article.
-
The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic.Brain Behav Immun. 2022 May;102:89-97. doi: 10.1016/j.bbi.2022.02.018. Epub 2022 Feb 16. Brain Behav Immun. 2022. PMID: 35181440 Free PMC article.
-
Fatigue, depression, and pain in multiple sclerosis: How neuroinflammation translates into dysfunctional reward processing and anhedonic symptoms.Mult Scler. 2022 Jun;28(7):1020-1027. doi: 10.1177/1352458520972279. Epub 2020 Nov 12. Mult Scler. 2022. PMID: 33179588 Free PMC article. Review.
References
-
- Leo RJ. Chronic pain and comorbid depression. Curr Treat Options Neurol 2005; 7(5): 403–412. - PubMed
-
- Linton SJ. A review of psychological risk factors in back and neck pain. Spine (Phila Pa 1976) 2000; 25(9): 1148–1156. - PubMed
-
- Pincus T, Burton AK, Vogel S, Field AP. A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain. Spine (Phila Pa 1976) 2002; 27(5): E109–120. - PubMed
-
- Wasan AD, Davar G, Jamison R. The association between negative affect and opioid analgesia in patients with discogenic low back pain. Pain 2005; 117(3): 450–461. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous