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Review
. 2024 Sep 13;12(9):2097.
doi: 10.3390/biomedicines12092097.

The Link between Endogenous Pain Modulation Changes and Clinical Improvement in Fibromyalgia Syndrome: A Meta-Regression Analysis

Kevin Pacheco-Barrios  1   2 , Rafaela Machado Filardi  1 , Luis Fernando González-González  1 , Nayeon Park  1   3 , Fernanda Queiroz Petrus  1 , Alba Navarro-Flores  4 , Silvia Di-Bonaventura  1   5   6 , Luana Gola Alves  1 , Fernanda Queiroz  1 , Felipe Fregni  1
Affiliations
Review

The Link between Endogenous Pain Modulation Changes and Clinical Improvement in Fibromyalgia Syndrome: A Meta-Regression Analysis

Kevin Pacheco-Barrios et al. Biomedicines. .

Abstract

Conditioned pain modulation (CPM) and temporal summation (TS) tests can measure the ability to inhibit pain in fibromyalgia syndrome (FMS) patients and its level of pain sensitization, respectively. However, their clinical validity is still unclear. We studied the association between changes in the CPM and TS tests and the clinical improvement of FMS patients who received therapeutic intervention. We systematically searched for FMS randomized clinical trials with data on therapeutic interventions comparing clinical improvement (pain intensity and symptom severity reduction), CPM, and TS changes relative to control interventions. To study the relationship between TS/CPM and clinical measures, we performed a meta-regression analysis to calculate odds ratios. We included nine studies (484 participants). We found no significant changes in TS or CPM by studying all the interventions together. Our findings show that this lack of difference is likely because pharmacological and non-pharmacological interventions resulted in contrary effects. Non-pharmacological interventions, such as non-invasive neuromodulation, showed the largest effects normalizing CPM/TS. Meta-regression was significantly associated with pain reduction and symptom severity improvement with normalization of TS and CPM. We demonstrate an association between clinical improvement and TS/CPM normalization in FMS patients. Thus, the TS and CPM tests could be surrogate biomarkers in FMS management. Recovering defective endogenous pain modulation mechanisms by targeted non-pharmacological interventions may help establish long-term clinical recovery in FMS patients.

Keywords: biomarker; chronic pain; conditioned pain modulation; fibromyalgia; temporal summation.

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Conflict of interest statement

Author Nayeon Park is a consultant at Admission AG. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
Flowchart of the study selection process.
Figure 2
Figure 2
Forest plots of the meta-analysis of the main outcomes (VAS pain and TS) [22,23,24,25,26,27,28,29,30]. (A) VAS score changes, (B) Temporal summation raw score changes, (C) Temporal summation as percentage change.
Figure 3
Figure 3
Forest plots of the meta-analysis of the main outcomes (FIQR pain and CPM) [23,24,25,26,27,28,29,30]. (A) FIQR score changes. (B) CPM raw score changes. (C) CPM as percentage change.
See this image and copyright information in PMC

References

    1. Kocyigit B.F., Akyol A. Fibromyalgia syndrome: Epidemiology, diagnosis and treatment. Reumatologia. 2022;60:413–421. doi: 10.5114/reum.2022.123671. - DOI - PMC - PubMed
    1. Nijs J., Malfliet A., Nishigami T. Nociplastic pain and central sensitization in patients with chronic pain conditions: A terminology update for clinicians. Braz. J. Phys. Ther. 2023;27:100518. doi: 10.1016/j.bjpt.2023.100518. - DOI - PMC - PubMed
    1. Mezhov V., Guymer E., Littlejohn G. Central sensitivity and fibromyalgia. Intern. Med. J. 2021;51:1990–1998. doi: 10.1111/imj.15430. - DOI - PubMed
    1. Pacheco-Barrios K., Teixeira P.E., Martinez-Magallanes D., Neto M.S., Pichardo E.A., Camargo L., Lima D., Cardenas-Rojas A., Fregni F. Brain compensatory mechanisms in depression and memory complaints in fibromyalgia: The role of theta oscillatory activity. Pain Med. 2024;25:514–522. doi: 10.1093/pm/pnae030. - DOI - PMC - PubMed
    1. Camargo L., Pacheco-Barrios K., Marques L.M., Caumo W., Fregni F. Adaptive and Compensatory Neural Signatures in Fibromyalgia: An Analysis of Resting-State and Stimulus-Evoked EEG Oscillations. Biomedicines. 2024;12:1428. doi: 10.3390/biomedicines12071428. - DOI - PMC - PubMed

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