Electroacupuncture Improves Nociceptive and Nociplastic Pain Via Brain Sensory Network Modulation
Poster No:
2042
Submission Type:
Abstract Submission
Authors:
Apeksha Sridhar1, Eric Ichesco2, Ishtiaq Mawla1, Brock Pluimer1, Steven Harte2, Robert Edwards3, Vitaly Napadow4, Richard Harris1
Institutions:
1Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine, Irvine, CA, 2Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI, 3Dept of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, HMS, Boston, MA, 4Center for Integrative Pain Neuroimaging, Martinos Center, MGH, HMS, Boston, MA
First Author:
Apeksha Sridhar
Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine
Irvine, CA
Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine
Irvine, CA
Co-Author(s):
Eric Ichesco
Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan
Ann Arbor, MI
Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan
Ann Arbor, MI
Ishtiaq Mawla
Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine
Irvine, CA
Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine
Irvine, CA
Brock Pluimer
Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine
Irvine, CA
Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine
Irvine, CA
Steven Harte
Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan
Ann Arbor, MI
Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan
Ann Arbor, MI
Robert Edwards
Dept of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, HMS
Boston, MA
Dept of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, HMS
Boston, MA
Richard Harris
Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine
Irvine, CA
Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine
Irvine, CA
Introduction:
Chronic pain may arise from diverse and overlapping mechanisms, including nociceptive pain originating from peripheral tissues and nociplastic pain caused by central nervous system dysregulation (Woolf, 2011). Fibromyalgia (FM), a complex chronic pain condition, exemplifies the interplay of these mechanisms, with widespread nociplastic pain often co-occurring with heightened sensitivity to experimental nociceptive stimuli (Clauw, 2014). Electroacupuncture (EA), a technique combining traditional acupuncture with electrical stimulation, has shown promise in alleviating pain in FM (Salazar, 2017). This study investigates how EA alters brain activation and functional connectivity (FC) in pain-processing regions, providing mechanistic insights to optimize its use in FM.
Methods:
Our analysis included 44 FM female participants from a previously published trial. Participants were randomized to receive either EA or Mock Laser {ML; sham treatment lacking sensory components) over eight sessions in four weeks (EA: n = 19; ML: n = 25). fMRI was conducted pre- and post-intervention on a 3T scanner with a block design alternating between rest and pressure-pain stimuli, calibrated to 30% of pain tolerance applied to the left thumb to evoke nociceptive pain. Pressure-pain tolerance (PPTol), and widespread nociplastic pain, assessed using the Michigan Body Map, were also recorded pre- and post-treatment outside the scanner. Data were preprocessed using fMRIPrep, and BOLD responses were modeled in SPM12 to assess brain activation during nociceptive-initiated pain compared to rest. Group differences in activation with widespread pain were then evaluated using pain scores as a covariate (voxel p < 0.001, uncorrected; cluster p < 0.05, FWE-corrected). FC analyses in the CONN toolbox used generalized psychophysiological interaction (gPPI; Pain> Rest) to assess group differences in FC relationships with widespread pain. Seed-to-whole-brain FC analyses utilized six bilateral insula regions (Taylor et al., 2009) and activation clusters as seeds. Mediation analyses in SPSS (PROCESS macro) examined pathways linking changes in PPtol, activation, and FC to reductions in widespread pain. Spearman correlations evaluated the relationship between PPTol and widespread pain.
Results:
The EA group showed a significant link between increased PPtol and reduced widespread pain (rho = -0.48, p = 0.036), an effect absent in ML (rho = -0.01, p = 0.94). EA-related increases in bilateral primary somatosensory cortices (S1), cingulate cortex, and precuneus activation were associated with reduced widespread pain (p < 0.05) and mediated the relationship between increased PPtol and pain reduction (e.g., left S1 indirect effect: β = -0.42, p < 0.05). Enhanced FC between the right anterior insula (R aIC) and left S1 in EA was associated with larger nociplastic widespread pain reductions (rho = -0.76, p < 0.001). Put together, S1 activation and subsequent S1–insula FC jointly mediated the relationship between increased PPtol and reduced widespread pain (indirect effect: β = -0.50, p < 0.05). In contrast, ML showed decreased R aIC – precuneus FC linked to widespread pain reduction (rho = 0.80, p < 0.001). Mediation further revealed that decreased precuneus activation contributed to reduced R aIC–precuneus FC and ultimately to reduced widespread pain in ML (indirect effect: β = -0.32, p < 0.05).
·Mechanistic Pathway of Electroacupuncture: Mediation Model
Conclusions:
Our findings suggest that EA may modulate nociceptive-initiated and nociplastic pain via a bottom-up pathway, where increased PPtol post treatment enhances S1 activation, strengthens S1-insula FC, and then reduces widespread pain. These results support the role of EA in engaging sensory and interoceptive networks to recalibrate pain perception (Mawla et al., 2021). In contrast, ML may reduce pain through a top-down mechanism, marked by decreased precuneus activation and reduced R aIC–precuneus FC, consistent with research suggesting that decreasing insula-DMN FC may reduce pain in FM (Napadow et al., 2012).
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Connectivity (eg. functional, effective, structural)
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 1
Perception: Tactile/Somatosensory
Keywords:
FUNCTIONAL MRI
Pain
Somatosensory
Treatment
Other - electroacupuncture; fibromyalgia; mediation
1|2Indicates the priority used for review
Abstract Information
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Mawla, I., Ichesco, E., Zöllner, H. J., Edden, R. A., Chenevert, T., Buchtel, H., Bretz, M. D., Sloan, H., Kaplan, C. M., Harte, S. E., Mashour, G. A., Clauw, D. J., Napadow, V., & Harris, R. E. (2021). Greater Somatosensory afference with acupuncture increases primary somatosensory connectivity and alleviates fibromyalgia pain via insular γ‐aminobutyric acid: A randomized neuroimaging trial. Arthritis & Rheumatology, 73(7), 1318–1328. https://doi.org/10.1002/art.41620
Napadow, V., Kim, J., Clauw, D. J., & Harris, R. E. (2012). Brief report: Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. Arthritis & Rheumatism, 64(7), 2398–2403. https://doi.org/10.1002/art.34412
Salazar, A. P. (2017). Electric stimulation for pain relief in patients with fibromyalgia: A systematic review and meta-analysis of randomized controlled trials. Pain Physician, 2(20;2), 15–25. https://doi.org/10.36076/ppj/2017/25
Taylor, K. S., Seminowicz, D. A., & Davis, K. D. (2009). Two systems of resting state connectivity between the insula and cingulate cortex. Human Brain Mapping, 30(9), 2731–2745. https://doi.org/10.1002/hbm.20705
Woolf, C. J. (2011). Central sensitization: Implications for the diagnosis and treatment of pain. Pain, 152(3). https://doi.org/10.1016/j.pain.2010.09.030