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rTMS Pain Reduction Effectiveness in Non-specific Chronic Low Back Pain Patients using rs-fMRI Functional Connectivity

Abstract

Purpose

Non-specific chronic low back pain (CLBP) is the most common form of CLBP without clear clinical evidence. This study evaluated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a noninvasive technique for pain reduction in non-specific CLBP using functional connectivity (FC) method.

Methods

Fifteen participants with non-specific CLBP received 20 Hz rTMS over the motor cortex. The pain intensity was measured using a Visual Analog Scale (VAS), and brain functional scans were obtained before and after brain stimulation. The percentage pain reduction (PPR%) and the FC differences in the insula (INS), thalamus (THA), supplementary motor area (SMA), and anterior cingulate cortex (ACC) were determined using paired t-test analysis. The correlation between PPR% and FCs was explored using the Pearson correlation coefficient.

Results

Pain intensity reduced significantly after rTMS (P < 0.05). FC between bilateral SMA and ACC, and bilateral INS decreased while the FC between bilateral INS and bilateral THA increased following rTMS. Moreover, there was a negative correlation between the FC of INS (R)-SMA (R) and that of PPR% (r=-0.56).

Conclusion

FC between SMA and INS was associated with analgesia of rTMS in non-specific CLBP, indicating the potential role of FC as a novel objective parameter to predict the outcome of clinical use of rTMS for pain relief in CLBP patients.

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References

  1. Balagué, F., Mannion, A. F., Pellisé, F., & Cedraschi, C. (2012). Non-specific low back pain. The lancet, 379, 482–491

    Article  Google Scholar 

  2. Hartvigsen, J., Hancock, M. J., Kongsted, A., Louw, Q., Ferreira, M. L., Genevay, S., et al. (2018). What low back pain is and why we need to pay attention. The Lancet, 391, 2356–2367

    Article  Google Scholar 

  3. Hoy, D., Brooks, P., Blyth, F., & Buchbinder, R. (2010). The epidemiology of low back pain. Best practice & research Clinical rheumatology. ;24:769 – 81

  4. Krismer, M., & Van Tulder, M. (2007). Low back pain (non-specific). Best practice & research clinical rheumatology, 21, 77–91

    CAS  Article  Google Scholar 

  5. Ng, S. K., Urquhart, D. M., Fitzgerald, P. B., Cicuttini, F. M., Hussain, S. M., & Fitzgibbon, B. M. (2018). The relationship between structural and functional brain changes and altered emotion and cognition in chronic low back pain brain changes. The Clinical journal of pain, 34, 237–261

    Article  Google Scholar 

  6. Machado, L., Kamper, S., Herbert, R., Maher, C., & McAuley, J. (2009). Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials. Rheumatology, 48, 520–527

    CAS  Article  Google Scholar 

  7. Oliveira, C. B., Maher, C. G., Pinto, R. Z., Traeger, A. C., Lin, C. W. C., Chenot, J. F., et al. (2018). Clinical practice guidelines for the management of non-specific low back pain in primary care: an updated overview. European Spine Journal, 27, 2791–2803

    Article  Google Scholar 

  8. Qaseem, A., Wilt, T. J., McLean, R. M., & Forciea, M. A. (2017). Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Annals of internal medicine, 166, 514–530

    Article  Google Scholar 

  9. Yang, S., & Chang, M. C. (2020). Effect of repetitive transcranial magnetic stimulation on pain management: a systematic narrative review. Frontiers in neurology, 11, 114

    Article  Google Scholar 

  10. Ambriz-Tututi, M., Alvarado‐Reynoso, B., & Drucker‐Colín, R. (2016). Analgesic effect of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic low back pain. Bioelectromagnetics, 37, 527–535

    CAS  Article  Google Scholar 

  11. Johnson, S., Summers, J., & Pridmore, S. (2006). Changes to somatosensory detection and pain thresholds following high frequency repetitive TMS of the motor cortex in individuals suffering from chronic pain. Pain, 123, 187–192

    Article  Google Scholar 

  12. Lefaucheur, J. P. (2016). Cortical neurostimulation for neuropathic pain: state of the art and perspectives. Pain, 157, S81–S9

    Article  Google Scholar 

  13. Hosomi, K., Shimokawa, T., Ikoma, K., Nakamura, Y., Sugiyama, K., Ugawa, Y., et al. (2013). Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial. PAIN®, 154, 1065–1072

    Article  Google Scholar 

  14. Lefaucheur, J., Drouot, X., & Nguyen, J. (2001). Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex. Neurophysiologie Clinique/Clinical Neurophysiology, 31, 247–252

    CAS  Article  Google Scholar 

  15. Ayache, S., Ahdab, R., Chalah, M., Farhat, W., Mylius, V., Goujon, C., et al. (2016). Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain. European Journal of Pain, 20, 1413–1422

    CAS  Article  Google Scholar 

  16. Nurmikko, T., MacIver, K., Bresnahan, R., et al. (2016). Motor Cortex Reorganization and Repetitive Transcranial Magnetic Stimulation for Pain—A Methodological Study. Neuromodulation: Technology at the Neural Interface J. ;19:669 – 78

  17. Lefaucheur, J., Drouot, X., Menard-Lefaucheur, I., Zerah, F., Bendib, B., Cesaro, P., et al. (2004). Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain. Journal of Neurology Neurosurgery & Psychiatry, 75, 612–616

    Article  Google Scholar 

  18. Jalalvandi, M., Alam, N. R., Sharini, H., Hashemi, H., & Nadimi, M. (2021). Brain Cortical Activation during Imagining of the Wrist Movement Using Functional Near-Infrared Spectroscopy (fNIRS). Journal of Biomedical Physics & Engineering, 11, 583

    Article  Google Scholar 

  19. Sharini, H., Alam, N. R., Khabiri, H., Arabalibeik, H., Hashemi, H., Azimi, A., et al. (2020). Novel FMRI-Compatible wrist robotic device for brain activation assessment during rehabilitation exercise. Medical engineering & physics, 83, 112–122

    CAS  Article  Google Scholar 

  20. Eqlimi, E., Alam, N. R., Sahraian, M., Eshaghi, A., Alam, S. R., Ghanaati, H., et al. (2014). Resting state functional connectivity analysis of multiple sclerosis and neuromyelitis optica using graph theory. XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013: Springer; p. 206-9

  21. Choi, G., & Chang, M. C. (2018). Effects of high-frequency repetitive transcranial magnetic stimulation on reducing hemiplegic shoulder pain in patients with chronic stoke: a randomized controlled trial. International Journal of Neuroscience, 128, 110–116

    Article  Google Scholar 

  22. Williams, J. A., Imamura, M., & Fregni, F. (2009). Updates on the Use of Non-invasive Brain Stimulation in Physical and Rehabilitation Medicine. rehabilitation medicine J, 41, 305–311

    Article  Google Scholar 

  23. Morton, D. L., Sandhu, J. S., & Jones, A. K. (2016). Brain imaging of pain: state of the art. Journal of pain research, 9, 613

    Article  Google Scholar 

  24. Friston, K. J., Frith, C. D., Liddle, P. F., & Frackowiak, R. S. (1993). Functional connectivity: the principal-component analysis of large (PET) data sets. Journal of Cerebral Blood Flow & Metabolism, 13, 5–14

    CAS  Article  Google Scholar 

  25. Davis, K. D., & Moayedi, M. (2013). Central mechanisms of pain revealed through functional and structural MRI. Journal of Neuroimmune Pharmacology, 8, 518–534

    Article  Google Scholar 

  26. Tagliazucchi, E., Balenzuela, P., Fraiman, D., & Chialvo, D. R. (2010). Brain resting state is disrupted in chronic back pain patients. Neuroscience letters, 485, 26–31

    CAS  Article  Google Scholar 

  27. Borsook, D., & Becerra, L. R. (2006). Breaking down the barriers: fMRI applications in pain, analgesia and analgesics. Molecular pain, 2, 30

    Article  Google Scholar 

  28. González-Roldán, A. M., Terrasa, J. L., Sitges, C., van der Meulen, M., Anton, F., & Montoya, P. (2020). Age-related changes in pain perception are associated with altered functional connectivity during resting state. Frontiers in Aging Neuroscience, 12, 116

    Article  Google Scholar 

  29. Baliki, M. N., Mansour, A. R., Baria, A. T., et al. (2014). Functional Reorganization of the Default Mode Network Across Chronic Pain Conditions. PloS one J. ;9:e106133

  30. Malinen, S., Vartiainen, N., Hlushchuk, Y., Koskinen, M., Ramkumar, P., Forss, N., et al. (2010). Aberrant temporal and spatial brain activity during rest in patients with chronic pain. Proceedings of the National Academy of Sciences. ;107:6493-7

  31. Yu, R., Gollub, R. L., Spaeth, R., Napadow, V., Wasan, A., & Kong, J. (2014). Disrupted functional connectivity of the periaqueductal gray in chronic low back pain. NeuroImage: Clinical, 6, 100–108

    Article  Google Scholar 

  32. Tu, Y., Jung, M., Gollub, R. L., Napadow, V., Gerber, J., Ortiz, A., et al. (2019). Abnormal medial prefrontal cortex functional connectivity and its association with clinical symptoms in chronic low back pain. Pain, 160, 1308–1318

    Article  Google Scholar 

  33. Balenzuela, P., Chernomoretz, A., Fraiman, D., et al. (2010). Modular Organization of Brain Resting State Networks in Chronic Back Pain Patients. Frontiers in neuroinformatics J. ;4:116

  34. Zhang, B., Jung, M., Tu, Y., Gollub, R., Lang, C., Ortiz, A., et al. (2019). Identifying brain regions associated with the neuropathology of chronic low back pain: a resting-state amplitude of low-frequency fluctuation study. British Journal of Anaesthesia, 123, e303–e11

    Article  Google Scholar 

  35. Xiang, A., Yu, Y., Jia, X., Ma, H., Liu, H., Zhang, Y., et al. (2019). The low-frequency BOLD signal oscillation response in the insular associated to immediate analgesia of ankle acupuncture in patients with chronic low back pain. Journal of pain research, 12, 841

    Article  Google Scholar 

  36. Baliki, M. N., Chialvo, D. R., Geha, P. Y., Levy, R. M., Harden, R. N., Parrish, T. B., et al. (2006). Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain. Journal of Neuroscience, 26, 12165–12173

    CAS  Article  Google Scholar 

  37. Zhang, S., Wu, W., Yang, J., & Wang, C. (2017). Abnormal spontaneous brain activity in acute low-back pain revealed by resting-state functional MRI. American journal of physical medicine & rehabilitation, 96, 253–259

    Article  Google Scholar 

  38. Li, J., Zhang, J. H., Yi, T., Tang, W. J., Wang, S. W., & Dong, J. C. (2014). Acupuncture treatment of chronic low back pain reverses an abnormal brain default mode network in correlation with clinical pain relief. Acupuncture in Medicine, 32, 102–108

    CAS  Article  Google Scholar 

  39. Seminowicz, D. A., Wideman, T. H., Naso, L., et al. (2011). Effective Treatment of Chronic Low Back Pain in Humans Reverses Abnormal Brain Anatomy and Function. Neuroscience J. ;31:7540-50

  40. Baliki, M. N., Geha, P. Y., Jabakhanji, R., Harden, N., Schnitzer, T. J., & Apkarian, A. V. (2008). A preliminary fMRI study of analgesic treatment in chronic back pain and knee osteoarthritis. Molecular pain. ;4:1744-8069-4-47

  41. Yabuki, S., Konno, S., & Kikuchi, S. (2013). Assessment of pain due to lumbar spine diseases using MR spectroscopy: a preliminary report. Journal of Orthopaedic Science, 18, 363–368

    Article  Google Scholar 

  42. Quesada, C., Pommier, B., Fauchon, C., Bradley, C., Créac’h, C., Murat, M., et al. (2020). New procedure of high-frequency repetitive transcranial magnetic stimulation for central neuropathic pain: a placebo-controlled randomized crossover study. Pain, 161, 718–728

    CAS  Article  Google Scholar 

  43. Galhardoni, R., Correia, G. S., Araujo, H., Yeng, L. T., Fernandes, D. T., Kaziyama, H. H., et al. (2015). Repetitive transcranial magnetic stimulation in chronic pain: a review of the literature. Archives of physical medicine and rehabilitation, 96, S156–S72

    Article  Google Scholar 

  44. Baliki, M. N., Petre, B., Torbey, S., Herrmann, K. M., Huang, L., Schnitzer, T. J., et al. (2012). Corticostriatal functional connectivity predicts transition to chronic back pain. Nature neuroscience, 15, 1117

    CAS  Article  Google Scholar 

  45. Kobayashi, Y., Kurata, J., Sekiguchi, M., Kokubun, M., Akaishizawa, T., Chiba, Y., et al. (2009). Augmented cerebral activation by lumbar mechanical stimulus in chronic low back pain patients: an FMRI study. Spine, 34, 2431–2436

    Article  Google Scholar 

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Acknowledgements

The authors thank with grateful appreciation for technical support by the staffs in National Brain Mapping Lab (NBML), Tehran, Iran. This study was part of the Ph.D thesis of Mahboubeh Masoumbeigi.

Funding

The research leading to these results received funding from research chancellor of Tehran University of Medical Sciences (TUMS) Tehran, Iran (Grant number: 97-03-30-40194).

Author information

Authors and Affiliations

Authors

Contributions

Mahboubeh Masoumbeigi performed the data acquisition, fMRI analysis, interpretation of data, and drafting the work as the principal author. Nader Riyahi Alam designed the main conception of this work and approved the final version to be published. Ramin Kordi, Mohsen Rostami, Mahdieh Afzali, and Mohadeseh Yadollahi contributed to the recruitment and clinical assessment of the patients. Abbas Rahimi foroushani analyzed the results statistically. Amir Homayoun Jafari and Hasan Hashemi revised the manuscript critically for important intellectual content. Mahsa Kavousi contributed to the data acquisition.

Corresponding author

Correspondence to Nader Riyahi Alam.

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Conflict of interest

The authors have no conflict of interest.

Ethical approval:

The protocol of the human study was approved by the local ethical committee, Tehran University of Medical Sciences (TUMS), Tehran, Iran (Approval number: IR.TUMS.MEDICINE.REC.1397.957).

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Masoumbeigi, M., Alam, N.R., Kordi, R. et al. rTMS Pain Reduction Effectiveness in Non-specific Chronic Low Back Pain Patients using rs-fMRI Functional Connectivity. J. Med. Biol. Eng. (2022). https://doi.org/10.1007/s40846-022-00721-8

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  • DOI: https://doi.org/10.1007/s40846-022-00721-8

Keywords

  • Non-specific CLBP
  • Pain Relief
  • rTMS effectiveness
  • rest-fMRI
  • Functional connectivity