Brain morphofunctional changes associated with pain in children, adolescents and young adults with sickle cell disease

Authors

DOI:

https://doi.org/10.17267/2965-3738bis.2023.e5299

Keywords:

Neuroimaging, Brain Morphofunctional Changes, Children, Adolescents, Young Adults, Sickle Cell Disease

Abstract

INTRODUCTION: Neuroimaging has been widely used to investigate the brain signature in patients with pain, but the results are heterogeneous, especially when the brain is under development, and in specific health conditions. Sickle cell disease (SCD) is often associated with chronic pain that starts in infancy, and there is a need to understand the brain of such children. OBJECTIVES: This systematic review aims to summarize the findings in the literature on brain morphofunctional changes in children, adolescents, young adults, and young adults with SCD. METHODS: Data search was performed in PubMed, LILACS, and SciELO, and results were organized to identify brain regions that showed significant structural and functional changes assessed through structural or functional MRI, or electroencephalography. RESULTS: The synthesis of five studies showed that children with SCD present decreased cerebral cortex thickness, and increased functional connectivity, mainly concentrated in the precuneus and anterior cingulate cortex, regions that make up the default mode network (DMN), and/or the pro-nociceptive network. DISCUSSION: These alterations were related to the frequency of pain and hospitalizations, and the increased connectivity in structures of the antinociceptive network is associated with a decrease in the frequency of pain crises and their consequences. CONCLUSION: Children, adolescents and young adults with SCD have decreased thickness and connectivity in the anterior cingulate cortex and precuneus.

References

(1) Lopes TS, Ballas SK, Santana JERS, Melo-Carneiro P, Oliveira LB, Sá KN, et al. Sickle cell disease chronic joint pain: Clinical assessment based on maladaptive central nervous system plasticity. Front Med. 2022;9:679053. https://doi.org/10.3389/fmed.2022.679053

(2) Saramba MI, Shakya S, Zhao D. Analgesic management of uncomplicated acute sickle-cell pain crisis in pediatrics: a systematic review and meta-analysis. J Pediatr. 2020;96(2):142-58. https://doi.org/10.1016/j.jped.2019.05.004

(3) Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020;161(9):1976-82. https://doi.org/10.1097/j.pain.0000000000001939

(4) Cançado RD, Jesus JA. Sickle cell disease in Brazil. Rev Bras Hematol Hemoter. 2007;29(3):203-6. https://doi.org/10.1590/S1516-84842007000300002

(5) Brandow AM, DeBaun MR. Key Components of Pain Management for Children and Adults with Sickle Cell Disease. Hematol Oncol Clin North Am. 2018;32(3):535-50. https://doi.org/10.1016/j.hoc.2018.01.014

(6) Farrell AT, Panepinto J, Carroll CP, Darbari DS, Desai AA, King AA, et al. End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain. Blood Adv. 2019;3(23):3982-4001. https://doi.org/10.1182/bloodadvances.2019000882

(7) Friedrichsdorf SJ, Goubert L. Pediatric pain treatment and prevention for hospitalized children. Pain Rep. 2020;5(1):e804. https://doi.org/10.1097%2FPR9.0000000000000804

(8) Darbari DS, Hampson JP, Ichesco E, Kadom N, Vezina G, Evangelou I, et al. Frequency of hospitalizations for pain and association with altered brain network connectivity in sickle cell disease. J Pain. 2015;16(11):1077-86. https://doi.org/10.1016%2Fj.jpain.2015.07.005

(9) Bhatt RR, Gupta A, Mayer EA, Zeltzer LK. Chronic pain in children: structural and resting-state functional brain imaging within a developmental perspective. Pediatr Res. 2020;88(6):840-9. https://doi.org/10.1038/s41390-019-0689-9

(10) McCarty PJ, Pines AR, Sussman BL, Wyckoff SN, Jensen A, Bunch R, et al. Resting State Functional Magnetic Resonance Imaging Elucidates Neurotransmitter Deficiency in Autism Spectrum Disorder. J Pers Med. 2021;11(10):969. https://doi.org/10.3390%2Fjpm11100969

(11) Müller-Putz GR. Electroencephalography. Handb Clin Neurol. 2020;168: 249-62. https://doi.org/10.1016/b978-0-444-63934-9.00018-4

(12) Colombatti R, Lucchetta M, Montanaro M, Rampazzo P, Ermani M, Talenti G, et al. Cognition and the Default Mode Network in Children with Sickle Cell Disease: A Resting State Functional MRI Study. PLoS One. 2016;11(6):e0157090. https://doi.org/10.1371/journal.pone.0157090

(13) Champlin G, Hwang SN, Heitzer A, Ding J, Jacola L, Estepp JH, et al. Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia. Exp Biol Med. 2021;246(23):2473-9. https://doi.org/10.1177/15353702211035778

(14) Case M, Shirinpour S, Vijayakumar V, Zhang H, Datta Y, Nelson S, Pergami P, Darbari DS, Gupta K, He B. Graph theory analysis reveals how sickle cell disease impacts neural networks of patients with more severe disease. Neuroimage Clin. 2019;21:101599. https://doi.org/10.1016/j.nicl.2018.11.009

(15) Zempsky WT, Stevens MC, Santanelli JP, Gaynor AM, Khadka S. Altered Functional Connectivity in Sickle Cell Disease Exists at Rest and During Acute Pain Challenge. Clin J Pain. 2017;33(12):1060-70. https://doi.org/10.1097/ajp.0000000000000492

(16) Silva RS, Silva VR. National Youth Policy: trajectory and challenges. Cad CRH [Internet]. 2011;24(63):663-78. https://doi.org/10.1590/S0103-49792011000300013

(17) Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-5. https://doi.org/10.1007/s10654-010-9491-z

(18) Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006;129(3):564-83. https://doi.org/10.1093/brain/awl004

(19) Goffaux P, Girard-Tremblay L, Marchand S, Daigle K, Whittingstall K. Individual differences in pain sensitivity vary as a function of precuneus reactivity. Brain Topogr. 2014;27(3):366-74. https://doi.org/10.1007/s10548-013-0291-0

(20) Yates TS, Ellis CT, Turk-Browne NB. Emergence and organization of adult brain function throughout child development. Neuroimage. 2021;226:117606. https://doi.org/10.1016/j.neuroimage.2020.117606

(21) Bliss TVP, Collingridge GL, Kaang B-K, Zhuo M. Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain. Nat Rev Neurosci. 2016;17(8):485-96. https://doi.org/10.1038/nrn.2016.68

(22) Xiao X, Zhang Y-Q. A new perspective on the anterior cingulate cortex and affective pain. Neurosci Biobehav Rev. 2018;90:200-11. https://doi.org/10.1016/j.neubiorev.2018.03.022

(23) Smith ML, Asada N, Malenka RC. Anterior cingulate inputs to nucleus accumbens control the social transfer of pain and analgesia. Science. 2021;371(6525):153-9. https://doi.org/10.1126/science.abe3040

(24) Leech R, Sharp DJ. The role of the posterior cingulate cortex in cognition and disease. Brain. 2014;137(1):12-32. https://doi.org/10.1093/brain/awt162

(25) Lichenstein SD, Verstynen T, Forbes EE. Adolescent brain development and depression: A case for the importance of connectivity of the anterior cingulate cortex. Neurosci Biobehav Rev. 2016;70:271-87. https://doi.org/10.1016/j.neubiorev.2016.07.024

(26) Zhan C, Liu Y, Wu K, Gao Y, Li X. Structural and Functional Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder: A Focus on Subgenual Anterior Cingulate Cortex. Brain Connect. 2017;7(2):106-114. https://doi.org/10.1089%2Fbrain.2016.0444

(27) Oblak AL, Gibbs TT, Blatt GJ. Decreased GABA(B) receptors in the cingulate cortex and fusiform gyrus in autism. J Neurochem. 2010;114(5):1414-23. https://doi.org/10.1111%2Fj.1471-4159.2010.06858.x

(28) Kuner R, Kuner T. Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain. Physiol Rev. 2021;101(1):213-58. https://doi.org/10.1152/physrev.00040.2019

(29) Veldhuijzen DS, Meeker TJ, Bauer D, Keaser ML, Gullapalli RP, Greenspan JD. Brain responses to painful electrical stimuli and cognitive tasks interact in the precuneus, posterior cingulate cortex, and inferior parietal cortex and do not vary across the menstrual cycle. Brain Behav. 2022;12(6):e2593. https://doi.org/10.1002%2Fbrb3.2593

(30) Thorp SL, Suchy T, Vadivelu N, Helander EM, Urman RD, Kaye AD. Functional Connectivity Alterations: Novel Therapy and Future Implications in Chronic Pain Management. Pain Physician. 2018;21(3):E207-E214. PMID: 29871376.

(31) Wang Y, Hardy SJ, Ichesco E, Zhang P, Harris RE, Darbari DS. Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease. Transl Res. 2022;240:17-25. https://doi.org/10.1016/j.trsl.2021.08.004

Downloads

Published

12/07/2023

Issue

Section

Reviews

How to Cite

1.
Marques C, Lopes L, Lucena R, Baptista A. Brain morphofunctional changes associated with pain in children, adolescents and young adults with sickle cell disease. Brain Imaging and Stimul. [Internet]. 2023 Dec. 7 [cited 2024 Apr. 27];2:e5299. Available from: https://journals.bahiana.edu.br/index.php/brain/article/view/5299

Most read articles by the same author(s)