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. 2023 Oct 13:17:1278183.
doi: 10.3389/fnins.2023.1278183. eCollection 2023.

Changes in alpha, theta, and gamma oscillations in distinct cortical areas are associated with altered acute pain responses in chronic low back pain patients

George Kenefati  1   2 , Mika M Rockholt  1   2 , Deborah Ok  1 , Michael McCartin  1 , Qiaosheng Zhang  1   2 , Guanghao Sun  1   2 , Julia Maslinski  1   2 , Aaron Wang  1   2 , Baldwin Chen  1   2 , Erich P Voigt  3 , Zhe Sage Chen  4   5   6 , Jing Wang  1   2   5 , Lisa V Doan  1   2
Affiliations

Changes in alpha, theta, and gamma oscillations in distinct cortical areas are associated with altered acute pain responses in chronic low back pain patients

George Kenefati et al. Front Neurosci. .

Abstract

Introduction: Chronic pain negatively impacts a range of sensory and affective behaviors. Previous studies have shown that the presence of chronic pain not only causes hypersensitivity at the site of injury but may also be associated with pain-aversive experiences at anatomically unrelated sites. While animal studies have indicated that the cingulate and prefrontal cortices are involved in this generalized hyperalgesia, the mechanisms distinguishing increased sensitivity at the site of injury from a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs are not well known.

Methods: We compared measured pain responses to peripheral mechanical stimuli applied to a site of chronic pain and at a pain-free site in participants suffering from chronic lower back pain (n = 15) versus pain-free control participants (n = 15) by analyzing behavioral and electroencephalographic (EEG) data.

Results: As expected, participants with chronic pain endorsed enhanced pain with mechanical stimuli in both back and hand. We further analyzed electroencephalographic (EEG) recordings during these evoked pain episodes. Brain oscillations in theta and alpha bands in the medial orbitofrontal cortex (mOFC) were associated with localized hypersensitivity, while increased gamma oscillations in the anterior cingulate cortex (ACC) and increased theta oscillations in the dorsolateral prefrontal cortex (dlPFC) were associated with generalized hyperalgesia.

Discussion: These findings indicate that chronic pain may disrupt multiple cortical circuits to impact nociceptive processing.

Keywords: alpha; chronic pain; electroencephalography; gamma; oscillations; source localization; theta.

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Conflict of interest statement

JW is a cofounder of Pallas Technologies, Inc., and ZSC is a scientific advisor of Pallas Technologies, Inc. JW and ZSC are inventors of a pending US patent application of pain treatment technology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Chronic low back pain participants show increased sensitivity in both back and hand compared with pain-free controls. Clustered box plots with median [interquartile range] for pain scores (numerical rating scale, 0–10) for stimuli applied to the dorsum of right hand (upper graph) and the lower back (lower graph) of pain-free controls and chronic pain participants. Participants with chronic lower back pain, as well as pain-free control participants, reported significantly higher pain scores for both low-intensity (32 mN) and high-intensity stimuli (256 mN) when applied to the dorsum of the hand (p < 0.001) and the lower back (p = 0.001 and p = 0.003, respectively). Outliers are represented by red circles and stars. Hypothesis testing was performed using the non-parametric Mann–Whitney test for independent groups.
Figure 2
Figure 2
EEG recording and source localization overview. (A) Example EEG from electrode Cz in a chronic pain participant during mechanical stimulation (256 mN) to the lower back (top) and hand (bottom). (B) Lateral and medial views of the brain and regions of interest (ROIs) used for source localization. Also shown are the MNI coordinates of the 3 (contralateral) ROIs in millimeter scale. ACC, anterior cingulate cortex; dlPFC, dorsolateral prefrontal cortex; mOFC, medial orbitofrontal cortex.
Figure 3
Figure 3
Trial-averaged time-frequency spectra with mechanical stimulation to the lower back with 256 mN. Time-frequency spectra (TFRs) are shown for example recordings from a chronic pain participant (left) and a pain-free control participant (right) for the 3 (contralateral) ROIs, (A) ACC; (B) dlPFC; (C) mOFC. Frequencies between 55 and 65 Hz (horizontal dashed line) omitted to remove electrical line noise. The TFRs represent percent change with respect to the baseline (−0.2–0.0 s before stimulus onset). ACC, anterior cingulate cortex; dlPFC, dorsolateral prefrontal cortex; mOFC, medial orbitofrontal cortex.
Figure 4
Figure 4
Mean theta and alpha band power are higher in the contralateral mOFC after mechanical stimulations to the lower back. (A) Mechanical stimulation with 256 mN results in a greater increase in the fold change of mean power in the theta (p = 0.0028) and alpha frequencies (p = 0.0034) of mOFC in participants with chronic low back pain (n = 15 participants and 144 trials) than pain-free controls (n = 15 participants and 143 trials). (B) Stimulation with 32 mN did not result in any statistically significant differences in the theta and alpha frequencies between chronic pain (n = 15 participants and 151 trials) and pain-free control participants (n = 15 participants and 143 trials). Data are shown as mean +/− SEM.
Figure 5
Figure 5
Trial-averaged time-frequency spectra with mechanical stimulation to the hand with 256 mN. Time-frequency spectra (TFRs) are shown for example recordings from a chronic pain participant (left) and a pain-free control participant (right) for the 3 (contralateral) ROIs, (A) ACC; (B) dlPFC; (C) mOFC. Frequencies between 55 and 65 Hz (hoirizontal dashed line) omitted to remove electrical line noise. The TFRs represent percent change with respect to the baseline (−0.2–0.0 s before stimulus onset). ACC, anterior cingulate cortex; dlPFC, dorsolateral prefrontal cortex; mOFC, medial orbitofrontal cortex.
Figure 6
Figure 6
Mean theta and high gamma band power are higher in the contralateral dlPFC and contralateral ACC, respectively, after mechanical stimulations to the hand. (A) Mechanical stimulation with 256 mN results in a greater fold increase in the mean power of the theta frequency band in the dlPFC of participants with chronic low back pain (n = 15 participants and 156 trials) than that of pain-free controls (n = 15 participants and 148 trials), p = 0.0385. (B) Mechanical stimulation with 256 mN results in a greater fold increase in the mean power of the high-gamma frequency band in the ACC of participants with chronic low back pain than that of pain-free controls, p = 0.0294. (C) Stimulation with 32 mN did not result in any statistically significant differences in the mean power of the theta frequency band in the dlPFC between chronic pain and pain-free control participants. (D) Stimulation with 32 mN did not result in any statistically significant differences in the mean power of the high-gamma frequency band in the ACC between chronic pain (n = 15 participants and 156 trials) and pain-free control participants (n = 15 participants and 147 trials). Data are shown as mean +/− SEM.
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References

    1. Apkarian A. V., Bushnell M. C., Treede R. D., Zubieta J. K. (2005). Human brain mechanisms of pain perception and regulation in health and disease. Eur. J. Pain 9, 463–484. doi: 10.1016/j.ejpain.2004.11.001 - DOI - PubMed
    1. Apkarian A. V., Hashmi J. A., Baliki M. N. (2011). Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 152, S49–S64. doi: 10.1016/j.pain.2010.11.010, PMID: - DOI - PMC - PubMed
    1. Apkarian A. V., Sosa Y., Sonty S., Levy R. M., Harden R. N., Parrish T. B., et al. . (2004). Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J. Neurosci. 24, 10410–10415. doi: 10.1523/JNEUROSCI.2541-04.2004, PMID: - DOI - PMC - PubMed
    1. Appelhoff S. H., Austin J., Lawrence A., Li A., Mantilla Ramos Y. J., O'Reilly C., et al. . (2022). PyPREP: a Python implementation of the preprocessing pipeline (PREP) for EEG data. Zenodo 2. doi: 10.5281/zenodo.6363576 - DOI
    1. Babiloni C., Babiloni F., Carducci F., Cincotti F., Rosciarelli F., Arendt-Nielsen L., et al. . (2002). Human brain oscillatory activity phase-locked to painful electrical stimulations: a multi-channel EEG study. Hum. Brain Mapp. 15, 112–123. doi: 10.1002/hbm.10013, PMID: - DOI - PMC - PubMed