Using Structural Equation Modeling to Investigate the Neural Basis of Altered Pain Processing in Fibromyalgia with Functional Magnetic Resonance Imaging
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Mar 26, 2024
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Abstract
Participants with fibromyalgia (FM) and healthy controls (HC) experienced an identical ‘threat/safety’ experimental pain paradigm while undergoing functional magnetic resonance imaging (fMRI) to investigate the differences in pain processing between the two groups. In the ‘threat’ (Pain) imaging runs, participants were told that they would receive noxious heat stimuli to their right hands, calibrated to elicit subjectively moderate levels of pain. In the ‘safety’ (No-Pain) imaging runs, no stimulus was given. This design enabled the study of both continuous and reactive components of pain processing, as well as brain activity associated with anticipation and reward. The fMRI data were analyzed with a data-driven structural equation modeling approach, and significant group-level connectivity differences were identified in both study conditions, in both time periods of interest (Expectation, Stimulation). Group-level connectivity differences in the No-Pain condition occurred mainly during the expectation of pain, and involved regions associated with emotion and reward, suggesting FM may involve altered affective/reward processing. Group-level connectivity differences in the Pain condition occurred mainly during stimulation, with the FM group having decreased connectivity between the anterior cingulate cortex (ACC) and the amygdala, and increased connectivity between the posterior cingulate cortex (PCC) and the thalamus. The decreased ACC→Amygdala connectivity supports previous findings, suggesting FM likely involves altered responses in motivational-affective aspects of pain processing. The increased PCC→Thalamus connectivity may suggest the FM group experienced heightened saliency toward the noxious stimuli, which may contribute toward the mechanism which causes hyperalgesia in FM.
Keywords:
human, pain, fibromyalgia, neuroimaging, MRI, functional MRI
Article Details
How to Cite
WARREN, Howard J. M. et al.
Using Structural Equation Modeling to Investigate the Neural Basis of Altered Pain Processing in Fibromyalgia with Functional Magnetic Resonance Imaging.
Medical Research Archives, [S.l.], v. 12, n. 3, mar. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5206>. Date accessed: 30 apr. 2024.
doi: https://doi.org/10.18103/mra.v12i3.5206.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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8. López-Solà M, Woo CW, Pujol J, et al. Towards a neurophysiological signature for fibromyalgia. Pain. 2017;158(1):34-47. doi:10.1097/j.pain.0000000000000707
9. Giesecke T, Gracely RH, Grant MAB, et al. Evidence of Augmented Central Pain Processing in Idiopathic Chronic Low Back Pain. Arthritis Rheum. 2004;50(2):613-623. doi:10.1002/art.20063
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11. Pujol J, López-Solà M, Ortiz H, et al. Mapping brain response to pain in fibromyalgia patients using temporal analysis of fMRI. PLoS One. 2009;4(4). doi:10.1371/journal.pone.0005224
12. Kim SH, Chang Y, Kim JH, et al. Insular cortex is a trait marker for pain processing in fibromyalgia syndrome - Blood oxygenation level-dependent functional magnetic resonance imaging study in Korea. Clin Exp Rheumatol. 2011;29(6 SUPPL. 69).
13. Kim J, Loggia ML, Cahalan CM, et al. The somatosensory link in fibromyalgia: Functional connectivity of the primary somatosensory cortex is altered by sustained pain and is associated with clinical/autonomic dysfunction. Arthritis Rheumatol. 2015;67(5):1395-1405. doi:10.1002/art.39043
14. 14. Craggs JG, Staud R, Robinson ME, Perlstein WM, Price DD. Effective connectivity among brain regions associated with slow temporal summation of C-fiber-evoked pain in fibromyalgia patients and healthy controls. J Pain. 2012;13(4):390-400. doi:10.1016/j.jpain.2012.01.002
15. Staud R, Craggs JG, Perlstein WM, Robinson ME, Price DD. Brain activity associated with slow temporal summation of C-fiber evoked pain in fibromyalgia patients and healthy controls. Eur J Pain. 2008;12(8):1078-1089. doi:10.1016/j.ejpain.2008.02.002
16. Schreiber KL, Loggia ML, Kim J, Cahalan CM, Napadow V, Edwards RR. Painful After-Sensations in Fibromyalgia are Linked to Catastrophizing and Differences in Brain Response in the Medial Temporal Lobe. J Pain. 2017;18(7):855-867. doi:10.1016/j.jpain.2017.02.437
17. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002;46(5): 1333-1343. doi:10.1002/art.10225
18. Warren HJ, Ioachim G, Powers JM, Stroman PW. How fMRI Analysis Using Structural Equation Modeling Techniques Can Improve Our Understanding of Pain Processing in Fibromyalgia. J Pain Res. 2021;Volume 14:381-398. doi:10.2147/jpr.s290795
19. Arnold LM, Bennett RM, Crofford LJ, et al. AAPT Diagnostic Criteria for Fibromyalgia. J Pain. 2019;20(6):611-628. doi:10.1016/j.jpain.2018.10.008
20. Fitzcharles MA, Perrot S, Häuser W. Comorbid fibromyalgia: A qualitative review of prevalence and importance. Eur J Pain (United Kingdom). 2018;22(9):1565-1576. doi:10.1002/ejp.1252
21. Arnold LM, Choy E, Clauw DJ, et al. Fibromyalgia and chronic pain syndromes: A white paper detailing current challenges in the field. Clin J Pain. 2016;32:737-746. doi:10.1097/AJP.0000000000000354
22. Lichtenstein A, Tiosano S, Amital H. The complexities of fibromyalgia and its comorbidities. Curr Opin Rheumatol. 2018;30(1):94-100. doi:10.1097/BOR.0000000000000464
23. Kulshreshtha P, Gupta R, Yadav RK, Bijlani RL, Deepak KK. A comprehensive study of autonomic dysfunction in the fibromyalgia patients. Clin Auton Res. 2012;22(3):117-122. doi:10.1007/s10286-011-0150-6
24. Kulshreshtha P, Deepak KK. Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: A mini review. Clin Physiol Funct Imaging. 2013;33(2):83-91. doi:10.1111/cpf.12000
25. Schmidt-Wilcke T, Diers M. New insights into the pathophysiology and treatment of fibromyalgia. Biomedicines. 2017;5(2):1-11. doi:10.3390/biomedicines5020022
26. Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience. 2016;338:114-129. doi:10.1016/j.neuroscience.2016.06.006
27. Price DD, Hu JW, Dubner R, Gracely RH. Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain. 1977;3:57-68.
28. Staud R, Robinson ME, Price DD. Temporal Summation of Second Pain and Its Maintenance Are Useful for Characterizing Widespread Central Sensitization of Fibromyalgia Patients. J Pain. 2007;8(11):893-901. doi:10.1016/j.jpain.2007.06.006
29. Stroman PW. Validation of structural equation modeling methods for functional MRI data acquired in the human brainstem and spinal cord. Crit Rev Biomed Eng. 2016;44(4):227-241. doi:10.1615/CritRevBiomedEng.2017020438
30. Stroman PW, Warren HJM, Ioachim G, Powers JM, McNeil K. A Comparison of the Effectiveness of Functional MRI Analysis Methods for Pain Research : The New Normal. 2020.
31. Spielberger CD. State-Trait Anxiety Inventory. In: The Corsini Encyclopedia of Psychology. ; 2010. doi:10.1002/9780470479216.corpsy0943
32. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. Inventory for Measuring Depression. Arch Gen Psychiatry. 1961:561-571.
33. Sletten DM, Suarez GA, Low PA, Mandrekar J, Singer W. COMPASS 31: A refined and abbreviated composite autonomic symptom score. Mayo Clin Proc. 2012;87(12):1196-1201. doi:10.1016/j.mayocp.2012.10.013
34. Adler GK, Geenen R. Hypothalamic-pituitary-adrenal and autonomic nervous system functioning in fibromyalgia. Rheum Dis Clin North Am. 2005;31(1):187-202. doi:10.1016/j.rdc.2004.10.002
35. Chalaye P, Goffaux P, Bourgault P, et al. Comparing pain modulation and autonomic responses in fibromyalgia and irritable bowel syndrome patients. Clin J Pain. 2012;28(6):519-526. doi:10.1097/AJP.0b013e31823ae69e
36. Chalaye P, Lafrenaye S, Goffaux P, Marchand S. The role of cardiovascular activity in fibromyalgia and conditioned pain modulation. Pain. 2014;155(6):1064-1069. doi:10.1016/j.pain.2013.12.023
37. Vincent A, Whipple MO, Low PA, Joyner M, Hoskin TL. Patients With Fibromyalgia Have Significant Autonomic Symptoms But Modest Autonomic Dysfunction. PM R. 2016;8(5):425-435. doi:10.1016/j.pmrj.2015.08.008
38. Crowne DP, Marlowe D. A new scale of social desirability independent of psychopathology. J Consult Psychol. 1960;24(4):349-354. doi:10.1037/h0047358
39. Sullivan MJL, Bishop SR, Pivik J. The Pain Catastrophizing Scale: Development and Validation. Psychol Assess. 1995;7(4):524-532.
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