The Effect of Duloxetine on Brain Neural Activity and Pain Processing in Patients with Knee Osteoarthritis: An fMRI-Based Study

Document Type : Original Article(s)

Authors

1 PhD Candidate of Medical Physics, Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 MSc of Biomedical Engineering, Department of Biomedical Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

3 Associate Professor of Biomedical Engineering, Department of Biomedical Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

4 PhD Student of Medical Imaging, Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

5 Associate Professor of Medical Physics, Department of Nuclear Medicine, School of Allied Medical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran

6 Associate Professor of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran

7 Assistant Professor of Biomedical Engineering, Department of Medical Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

10.48305/jims.v43.i817.0574

Abstract

Background: This study aimed to evaluate the effect of duloxetine on the pain matrix in the brains of patients with knee osteoarthritis (Osteoarthritis or OA) using functional Magnetic Resonance Imaging (fMRI).
Methods: The study was conducted using fMRI on 39 patients with knee osteoarthritis, divided into two groups: one receiving a placebo and the other group treated with duloxetine. Data analysis involved Independent Component Analysis (ICA) to identify brain networks and Graph Theory to assess functional connectivity within the pain matrix. All analyses were performed using the Statistical Parametric Mapping (SPM) toolbox and the functional connectivity toolbox (CONN) in MATLAB software.
Findings: Results: In the Independent Component Analysis (ICA) method, various brain regions such as the anterior cingulate cortex (ACC), thalamus (THL), insular cortex (IC), parietal cortex (PO), and frontal pole (FP) exhibited higher numbers of active voxels in both the placebo and duloxetine groups. Graph theory analysis revealed that in the placebo group, the left thalamus (THL-left) was functionally connected with the right parietal cortex (PO-right), and the left parietal cortex (PO-left) showed functional connections with the frontal pole (FP) and insular cortex (IC). In the duloxetine group, the left parietal cortex (PO-left) demonstrated functional connectivity with the frontal pole (FP).
Conclusion: The findings of this study demonstrate that duloxetine has a significant impact on the neural architecture and pain-related functional dynamics in patients with knee osteoarthritis. These results provide a foundation for future research in the fields of cognitive neuroscience and pharmacology.

Highlights

Yazdan Choghazardi: PubMed

Ayub Faramarzi: PubMed

Vahab Dehlaghi: PubMed

Maziar Jalalvandi: PubMed

Ehsan Khodamoradi: PubMed

Mitra Yousefpour: PubMed

Hamid Sharini: PubMed

Keywords

Main Subjects

References

  1. Vassão PG, Parisi J, Penha TFC, Balão AB, Renno ACM, Avila MA. Association of photobiomodulation therapy (PBMT) and exercises programs in pain and functional capacity of patients with knee osteoarthritis (KOA): a systematic review of randomized trials. Lasers Med Sci 2021; 36(7): 1341-53.
  2. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet 2010; 375(9715): 686–95.
  3. Glyn-Jones S, Palmer AJR, Agricola R, Price AJ, Vincent TL, Weinans H, et al. Osteoarthritis. Lancet 2015; 386(9991): 376–87.
  4. Lan F, Lin G, Cao G, Li Z, Ma D, Liu F, et al. Altered intrinsic brain activity and functional connectivity before and after knee arthroplasty in the elderly: A resting-state fMRI study. Front Neurol 2020; 11: 556028.
  5. World Health Organization. Global recommendations on physical activity for health. Geneva: World Health Organization; 2010;60.
  6. Bushman B, Medicine AC of S. ACSM’s Complete Guide to Fitness & Health. 2nd Ed. Champaign, IL: Human Kinetics; 2017.
  7. Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA 2021; 325(6): 568–78.
  8. Wenham CYJ, Grainger AJ, Conaghan PG. The role of imaging modalities in the diagnosis, differential diagnosis and clinical assessment of peripheral joint osteoarthritis. Osteoarthritis Cartilage 2014; 22(10): 1692–702.
  9. Giménez M, Pujol J, Ali Z, López-Solà M, Contreras-Rodríguez O, Deus J, et al. Naproxen effects on brain response to painful pressure stimulation in patients with knee osteoarthritis: a double-blind, randomized, placebo-controlled, single-dose study. J Rheumatol 2014; 41(11): 2240–8.
  10. Reckziegel D, Bailey H, Cottam WJ, Tench CR, Mahajan RP, Walsh DA, et al. Imaging pain relief in osteoarthritis (IPRO): protocol of a double-blind randomised controlled mechanistic study assessing pain relief and prediction of duloxetine treatment outcome. BMJ Open 2017; 7(6): e014013.
  11. Chen X, Spaeth RB, Retzepi K, Ott D, Kong J. Acupuncture modulates cortical thickness and functional connectivity in knee osteoarthritis patients. Sci Rep 2014; 4: 6482.
  12. Sharini H, Fooladi M, Masjoodi S, Jalalvandi M, Pour MY. Identification of the pain process by cold stimulation: Using dynamic causal modeling of effective connectivity in functional near-infrared spectroscopy (fNIRS). IRBM. 2019; 40(2): 86–94.
  13. Hyett MP, Breakspear MJ, Friston KJ, Guo CC, Parker GB. Disrupted effective connectivity of cortical systems supporting attention and interoception in melancholia. JAMA Psychiatry 2015; 72(4): 350–8.
  14. Kandilarova S, Stoyanov D, Kostianev S, Specht K. Altered resting state effective connectivity of anterior insula in depression. Front Psychiatry 2018; 9: 83.
  15. Tétreault P, Mansour A, Vachon-Presseau E, Schnitzer TJ, Apkarian AV, Baliki MN. Brain connectivity predicts placebo response across chronic pain clinical trials. PLoS Biol 2016; 14(10): e1002570.
  16. Tahmasian M, Bettray LM, van Eimeren T, Drzezga A, Timmermann L, Eickhoff CR, et al. A systematic review on the applications of resting-state fMRI in Parkinson’s disease: does dopamine replacement therapy play a role? Cortex 2015; 73: 80–105.
  17. Tae W-S, Lee S, Choi S, Pyun S-B. Effects of aging on brain networks during swallowing: general linear model and independent component analyses. Sci Rep 2021; 11(1): 1069.
  18. Ushio K, Nakanishi K, Mikami Y, Yoshino A, Takamura M, Hirata K, et al. Altered Resting-State Connectivity with Pain-Related Expectation Regions in Female Patients with Severe Knee Osteoarthritis. J Pain Res 2020; 13: 3227-34.
  19. Cottam WJ, Iwabuchi SJ, Drabek MM, Reckziegel D, Auer DP. Altered connectivity of the right anterior insula drives the pain connectome changes in chronic knee osteoarthritis. Pain 2018; 159(5): 929-38.
  20. Moss RA. Psychotherapy in pain management: New viewpoints and treatment targets based on a brain theory. AIMS Neurosci 2020; 7(3): 194.
  21. Ong W-Y, Stohler CS, Herr DR. Role of the prefrontal cortex in pain processing. Mol Neurobiol 2019; 56(2): 1137–66.
  22. Ploner M, Lee MC, Wiech K, Bingel U, Tracey I. Flexible cerebral connectivity patterns subserve contextual modulations of pain. Cereb Cortex 2011; 21(3): 719–26.
  23. Kamping S, Andoh J, Bomba IC, Diers M, Diesch E, Flor H. Contextual modulation of pain in masochists: involvement of the parietal operculum and insula. Pain 2016; 157(2): 445-55.
  24. Mansouri FA, Buckley MJ, Mahboubi M, Tanaka K. Behavioral consequences of selective damage to frontal pole and posterior cingulate cortices. Proc Natl Acad Sci U S A 2015; 112(29): E3940–9.
  25. Horing B, Sprenger C, Büchel C. The parietal operculum preferentially encodes heat pain and not salience. PLoS Biol 2019; 17(8): e3000205.
  26. Ammitzbøll N, Arendt-Nielsen L, Bertoli D, Brock C, Olesen AE, Kappel A, et al. A mechanism-based proof of concept study on the effects of duloxetine in patients with painful knee osteoarthritis. Trials 2021; 22(1): 958.
  27. López-Solà M, Pujol J, Hernández-Ribas R, Harrison BJ, Contreras-Rodríguez O, Soriano-Mas C, et al. Effects of duloxetine treatment on brain response to painful stimulation in major depressive disorder. Neuropsychopharmacology 2010; 35(11): 2305-17.
Journal of Isfahan Medical School
Volume 43, Issue 817
1st Week, August
July and August 2025
Pages 574-581

Files

History

  • Receive Date: 02 December 2024
  • Accept Date: 19 July 2025

Share

How to cite

Statistics