Korean J Pain.  2021 Oct;34(4):437-446. 10.3344/kjp.2021.34.4.437.

Cerebral current-source distribution associated with pain improvement by non-invasive painless signaling therapy in patients with failed back surgery syndrome

• Lee CH
• Kim HS
• Kim YS
• Jung S
• Yoon CH
• Kwon OY

• KMID: 2520751
• DOI: http://doi.org/10.3344/kjp.2021.34.4.437

Abstract

Background
Non-invasive painless signaling therapy (NPST) is an electro-cutaneous treatment that converts endogenous pain information into synthetic non-pain information. This study explored whether pain improvement by NPST in failed back surgery syndrome (FBSS) patients is related to cerebral modulation.
Methods
Electroencephalography (EEG) analysis was performed in 11 patients with FBSS. Subjects received daily NPST for 5 days. Before the first treatment, patients completed the Brief Pain Inventory (BPI) and Beck Depression Inventory and underwent baseline EEG. After the final treatment, they responded again to the BPI, reported the percent pain improvement (PPI), and then underwent post-treatment EEG. If the PPI grade was zero, they were assigned to the ineffective group, while all others were assigned to the effective group. We used standardized low-resolution brain electromagnetic tomography (sLORETA) to explore the EEG current-source distribution (CSD) associated with pain improvement by NPST.
Results
The 11 participants had a median age of 67.0 years, and 63.6% were female. The sLORETA images revealed a beta-2 CSD increment in 12 voxels of the right anterior cingulate gyrus (ACG) and the right medial frontal area. The point of maximal CSD changes was in the right ACG. The alpha band CSD increased in 2 voxels of the left transverse gyrus.
Conclusions
Pain improvement by NPST in FBSS patients was associated with increased cerebral activity, mainly in the right ACG. The change in afferent information induced by NPST seems to be associated with cerebral pain perception.

Keyword

Chronic Pain; Electric Stimulation Therapy; Electroencephalography; Failed Back Surgery Syndrome; Gyrus Cinguli; Information Theory; Neuroimaging; Neuronal Plasticity; Pain Perception

Figure

• 

  Fig. 1 Flow diagram of patient recruitment. The authors diagnosed 45 patients with failed back surgery syndrome. Fifteen patients of them ousted from the study because of age unsuitability or factors affecting pain sensitivity. Of the remaining 30 patients, 27 patients agreed to participate in the study. The authors also excluded 15 of the 27 patients due to depressive symptoms and lost another patient during follow-up. Finally, 11 patients were subjects for electroencephalography (EEG) analysis. Seven of them were in the effective group, and the remaining four in the ineffective group.

• 

  Fig. 2 Standardized low-resolution brain electromagnetic tomography (sLORETA) images showing beta-2 current-source distribution (CSD) associated with pain improvement by non-invasive painless signaling therapy. The beta-2 CSD increment was in the right anterior cingulate gyrus and the right medial frontal area. The number of suprathreshold voxels was 12 (P < 0.05, two-tailed). The location of the maximal point of CSD changes was the right anterior cingulate gyrus (Brodmann’s area 32, Montreal Neurological Institute coordinates: x = 10, y = 25, z = 25).

• 

  Fig. 3 Standardized low-resolution brain electromagnetic tomography (sLORETA) images showing alpha current-source distribution (CSD) associated with pain improvement by non-invasive painless signaling therapy. The alpha CSD increment was in the left transverse gyrus of the temporal lobe. The number of suprathreshold voxels was two (P < 0.05, two-tailed).

Reference

1. Hoy D, March L, Brooks P, Blyth F, Woolf A, Bain C, et al. 2014; The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 73:968–74. DOI: 10.1136/annrheumdis-2013-204428. PMID: 24665116.

2. Smith M, Davis MA, Stano M, Whedon JM. 2013; Aging baby boomers and the rising cost of chronic back pain: secular trend analysis of longitudinal Medical Expenditures Panel Survey data for years 2000 to 2007. J Manipulative Physiol Ther. 36:2–11. DOI: 10.1016/j.jmpt.2012.12.001. PMID: 23380209. PMCID: PMC3596008.

3. Rajaee SS, Bae HW, Kanim LE, Delamarter RB. 2012; Spinal fusion in the United States: analysis of trends from 1998 to 2008. Spine (Phila Pa 1976). 37:67–76. DOI: 10.1097/BRS.0b013e31820cccfb. PMID: 21311399.

4. Harvey AM. 1995; Classification of chronic pain-descriptions of chronic pain syndromes and definitions of pain terms. Clin J Pain. 11:163. https://journals.lww.com/clinicalpain/Citation/1995/06000/Classification_of_Chronic_Pain_Descriptions_of.24.aspx. DOI: 10.1097/00002508-199506000-00024. PMID: 3461421.

5. Diebo BG, Passias PG, Marascalchi BJ, Jalai CM, Worley NJ, Errico TJ, et al. 2015; Primary versus revision surgery in the setting of adult spinal deformity: a nationwide study on 10,912 patients. Spine (Phila Pa 1976). 40:1674–80. DOI: 10.1097/BRS.0000000000001114. PMID: 26267823.

6. Baber Z, Erdek MA. 2016; Failed back surgery syndrome: current perspectives. J Pain Res. 9:979–87. DOI: 10.2147/JPR.S92776. PMID: 27853391. PMCID: PMC5106227.

7. Freynhagen R, Bennett MI. 2009; Diagnosis and management of neuropathic pain. BMJ. 339:b3002. DOI: 10.1136/bmj.b3002. PMID: 19675082.

8. Ricci M, Pirotti S, Scarpi E, Burgio M, Maltoni M, Sansoni E, et al. 2012; Managing chronic pain: results from an open-label study using MC5-A Calmare®device. Support Care Cancer. 20:405–12. DOI: 10.1007/s00520-011-1128-6. PMID: 21394458.

9. Smith TJ, Coyne PJ, Parker GL, Dodson P, Ramakrishnan V. 2010; Pilot trial of a patient-specific cutaneous electrostimulation device (MC5-A Calmare®) for chemotherapy-induced peripheral neuropathy. J Pain Symptom Manage. 40:883–91. DOI: 10.1016/j.jpainsymman.2010.03.022. PMID: 20813492. PMCID: PMC4383258.

10. Shannon CE. 1948; A mathematical theory of communication. Bell Syst Tech J. 27:379–423. https://ieeexplore.ieee.org/abstract/document/6773024. DOI: 10.1002/j.1538-7305.1948.tb01338.x.

11. Craig AD, Reiman EM, Evans A, Bushnell MC. 1996; Functional imaging of an illusion of pain. Nature. 384:258–60. DOI: 10.1038/384258a0. PMID: 8918874.

12. Foltz EL, White LE Jr. 1962; Pain "relief" by frontal cingulumotomy. J Neurosurg. 19:89–100. DOI: 10.3171/jns.1962.19.2.0089. PMID: 13893868.

13. Levi V, Cordella R, D'Ammando A, Tringali G, Dones I, Messina G, et al. 2019; Dorsal anterior cingulate cortex (ACC) deep brain stimulation (DBS): a promising surgical option for the treatment of refractory thalamic pain syndrome (TPS). Acta Neurochir (Wien). 161:1579–88. DOI: 10.1007/s00701-019-03975-5. PMID: 31209628.

14. Peyron R, García-Larrea L, Grégoire MC, Costes N, Convers P, Lavenne F, et al. 1999; Haemodynamic brain responses to acute pain in humans: sensory and attentional networks. Brain. 122(Pt 9):1765–80. DOI: 10.1093/brain/122.9.1765. PMID: 10468515.

15. Sikes RW, Vogt BA. 1992; Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol. 68:1720–32. DOI: 10.1152/jn.1992.68.5.1720. PMID: 1479441.

16. Vaccarino AL, Melzack R. 1989; Analgesia produced by injection of lidocaine into the anterior cingulum bundle of the rat. Pain. 39:213–9. DOI: 10.1016/0304-3959(89)90008-0. PMID: 2594399.

17. Baumgärtner U, Tiede W, Treede RD, Craig AD. 2006; Laser-evoked potentials are graded and somatotopically organized anteroposteriorly in the operculoinsular cortex of anesthetized monkeys. J Neurophysiol. 96:2802–8. DOI: 10.1152/jn.00512.2006. PMID: 16899640.

18. Hofbauer RK, Fiset P, Plourde G, Backman SB, Bushnell MC. 2004; Dose-dependent effects of propofol on the central processing of thermal pain. Anesthesiology. 100:386–94. DOI: 10.1097/00000542-200402000-00031. PMID: 14739816.

19. Lee MC, Mouraux A, Iannetti GD. 2009; Characterizing the cortical activity through which pain emerges from nociception. J Neurosci. 29:7909–16. DOI: 10.1523/JNEUROSCI.0014-09.2009. PMID: 19535602. PMCID: PMC6665631.

20. Legrain V, Iannetti GD, Plaghki L, Mouraux A. 2011; The pain matrix reloaded: a salience detection system for the body. Prog Neurobiol. 93:111–24. DOI: 10.1016/j.pneurobio.2010.10.005. PMID: 21040755.

21. Peyron R, Laurent B, García-Larrea L. 2000; Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin. 30:263–88. DOI: 10.1016/S0987-7053(00)00227-6. PMID: 11126640.

22. Michel CM, Murray MM, Lantz G, Gonzalez S, Spinelli L, Grave de Peralta R. 2004; EEG source imaging. Clin Neurophysiol. 115:2195–222. DOI: 10.1016/j.clinph.2004.06.001. PMID: 15351361.

23. He B, Sohrabpour A, Brown E, Liu Z. 2018; Electrophysiological source imaging: a noninvasive window to brain dynamics. Annu Rev Biomed Eng. 20:171–96. DOI: 10.1146/annurev-bioeng-062117-120853. PMID: 29494213. PMCID: PMC7941524.

24. Gross J, Kujala J, Hämäläinen M, Timmermann L, Schnitzler A, Salmelin R. 2001; Dynamic imaging of coherent sources: studying neural interactions in the human brain. Proc Natl Acad Sci U S A. 98:694–9. DOI: 10.1073/pnas.98.2.694. PMID: 11209067. PMCID: PMC14650.

25. Davis KD, Flor H, Greely HT, Iannetti GD, Mackey S, Ploner M, et al. 2017; Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations. Nat Rev Neurol. 13:624–38. DOI: 10.1038/nrneurol.2017.122. PMID: 28884750.

26. Tracey I, Johns E. 2010; The pain matrix: reloaded or reborn as we image tonic pain using arterial spin labelling. Pain. 148:359–60. DOI: 10.1016/j.pain.2009.11.009. PMID: 20080346.

27. Bélanger M, Allaman I, Magistretti PJ. 2011; Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 14:724–38. DOI: 10.1016/j.cmet.2011.08.016. PMID: 22152301.

28. Logothetis NK. 2003; The underpinnings of the BOLD functional magnetic resonance imaging signal. J Neurosci. 23:3963–71. DOI: 10.1523/JNEUROSCI.23-10-03963.2003. PMID: 12764080. PMCID: PMC6741096.

29. Nguyen T, Potter T, Karmonik C, Grossman R, Zhang Y. 2018; Concurrent EEG and functional MRI recording and integration analysis for dynamic cortical activity imaging. J Vis Exp. 136:56417. DOI: 10.3791/56417. PMID: 30010646. PMCID: PMC6102018.

30. Seeber M, Cantonas LM, Hoevels M, Sesia T, Visser-Vandewalle V, Michel CM. 2019; Subcortical electrophysiological activity is detectable with high-density EEG source imaging. Nat Commun. 10:753. DOI: 10.1038/s41467-019-08725-w. PMID: 30765707. PMCID: PMC6376013.

31. Ramon C, Schimpf PH, Haueisen J. 2006; Influence of head models on EEG simulations and inverse source localizations. Biomed Eng Online. 5:10. DOI: 10.1186/1475-925X-5-10. PMID: 16466570. PMCID: PMC1389789.

32. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. 1961; An inventory for measuring depression. Arch Gen Psychiatry. 4:561–71. DOI: 10.1001/archpsyc.1961.01710120031004. PMID: 13688369.

33. Kwon OY, Park SP. 2013; Frequency of affective symptoms and their psychosocial impact in Korean people with epilepsy: a survey at two tertiary care hospitals. Epilepsy Behav. 26:51–6. DOI: 10.1016/j.yebeh.2012.10.020. PMID: 23207517.

34. Rhee MK, Lee YH, Park SH, Sohn CH, Chung YC, Hong SK, et al. 1995; A standardization study of Beck Depression Inventory 1 - Korean version (K-BDI): reliability and factor analysis. Korean J Psychopathol. 4:77–95. http://www.riss.kr/search/detail/DetailView.do?p_mat_type=1a0202e37d52c72d&control_no=6860a27c5da18618ffe0bdc3ef48d419.

35. Cleeland CS, Ladinsky JL, Serlin RC, Nugyen CT. 1988; Multidimensional measurement of cancer pain: comparisons of US and Vietnamese patients. J Pain Symptom Manage. 3:23–7. DOI: 10.1016/0885-3924(88)90134-0. PMID: 3351345.

36. Cleeland C. 1991; Research in cancer pain. What we know and what we need to know. Cancer. 67(3 Suppl):823–7. DOI: 10.1002/1097-0142(19910201)67:3+<823::AID-CNCR2820671412>3.0.CO;2-S. PMID: 1986852.

37. Yun YH, Mendoza TR, Heo DS, Yoo T, Heo BY, Park HA, et al. 2004; Development of a cancer pain assessment tool in Korea: a validation study of a Korean version of the brief pain inventory. Oncology. 66:439–44. DOI: 10.1159/000079497. PMID: 15452372.

38. Pascual-Marqui RD. 2002; Standardized low-resolution brain electromagnetic tomography (sLORETA): technical details. Methods Find Exp Clin Pharmacol. 24 Suppl D:5–12. PMID: 12575463.

39. R Core Team. 2020. R: a language and environment for statistical computing [Internet]. R Foundation for Statistical Computing;Vienna: Available at: https://www.R-project.org/.

40. Simić G, Hof PR. 2015; In search of the definitive Brodmann's map of cortical areas in human. J Comp Neurol. 523:5–14. DOI: 10.1002/cne.23636. PMID: 24889330.

41. Kragel PA, Kano M, Van Oudenhove L, Ly HG, Dupont P, Rubio A, et al. 2018; Generalizable representations of pain, cognitive control, and negative emotion in medial frontal cortex. Nat Neurosci. 21:283–9. DOI: 10.1038/s41593-017-0051-7. PMID: 29292378. PMCID: PMC5801068.

42. Zhang Y, Yu T, Qin B, Li Y, Song G, Yu B. 2016; Microstructural abnormalities in gray matter of patients with postherpetic neuralgia: a diffusional kurtosis imaging study. Pain Physician. 19:E601–11. DOI: 10.36076/ppj/2019.19.E601. PMID: 27228526.

43. Jiang L, Zuo XN. 2016; Regional homogeneity: a multimodal, multiscale neuroimaging marker of the human connectome. Neuroscientist. 22:486–505. DOI: 10.1177/1073858415595004. PMID: 26170004. PMCID: PMC5021216.

44. Zhang Y, Cao S, Yuan J, Song G, Yu T, Liang X. 2020; Functional and structural changes in postherpetic neuralgia brain before and six months after pain relieving. J Pain Res. 13:909–18. DOI: 10.2147/JPR.S246745. PMID: 32440196. PMCID: PMC7210030.

45. Koles ZJ. 1998; Trends in EEG source localization. Electroencephalogr Clin Neurophysiol. 106:127–37. DOI: 10.1016/S0013-4694(97)00115-6. PMID: 9741773.

46. Sharma P, Seeck M, Beniczky S. 2019; Accuracy of interictal and ictal electric and magnetic source imaging: a systematic review and meta-analysis. Front Neurol. 10:1250. DOI: 10.3389/fneur.2019.01250. PMID: 31849817. PMCID: PMC6901665.