Mitochondrial Imbalance as a New Approach to the Study of Fibromyalgia

Antonio Martínez-Lara, Ana María Moreno-Fernández, Maripaz Jiménez-Guerrero, Claudia Díaz-López, Manuel De-Miguel, David Cotán, José Antonio Sánchez-Alcázar, Antonio Martínez-Lara, Ana María Moreno-Fernández, Maripaz Jiménez-Guerrero, Claudia Díaz-López, Manuel De-Miguel, David Cotán, José Antonio Sánchez-Alcázar

Abstract

Background: Fibromyalgia (FM) is a common chronic pain disease, whose pathogenic mechanism still remains elusive. Oxidative stress markers and impaired bioenergetics homeostasis have been proposed as relevant events in the pathogenesis of the disease. Hence, the aim of the study is to analyse the potential biomarkers of mitochondrial imbalance in FM patients along with coenzyme Q10 (CoQ10) as a possible treatment.

Methods: The symptomatology of patients was recorded with an adaption of the Fibromyalgia Impact Questionnaire (FIQ). Mitochondrial imbalance was tested from blood extraction and serum isolation in 33 patients diagnosed with FM and 30 healthy controls. Western blot and HPLC techniques were performed to study the different parameters. Finally, bioinformatic analysis of machine learning was performed to predict possible associations of results.

Results: CoQ10 parameter did not show evidence to be a good marker of the disease, as the values are not significantly different between control and patient groups (Student's t-test, CI 95%). For this reason, the focus of the study changed into the ratio between mitochondrial mass and autophagy levels. The bioinformatics analysis showed a possible association between this ratio and patients' symptomatology. Finally, the effects of coenzyme Q10 as a potential treatment for the disease were different within patients, and its efficacy may be related to the initial mitochondrial status. However, there is no statistical significance due to limitations within the sample size.

Conclusion: Our study supports the hypothesis that an imbalance in mitochondrial homeostasis is involved in the FM pathogenesis. However, whether the increase in oxidative stress is the result of mitochondrial imbalance or the cause of this disease remains an open question. The measurement of this imbalance might be used as a preliminary biomarker for the diagnosis and follow-up of patients with FM, and even for the evaluation of the effects of the different antioxidants therapies.

Keywords: chronic pain; diagnosis; fibromyalgia; mitochondria.

Conflict of interest statement

Antonio Martínez-Lara, Maripaz Jiménez-Guerrero, Claudia Díaz-López, and David Cotán are employees of Pronacera Therapeutics S.L. The authors report no other potential conflicts of interest for this work and report no financial or commercial conflicts of interest.

© 2020 Martínez-Lara et al.

Figures

Figure 1
Figure 1
Coenzyme Q10 in control (left) and patient (right) groups expressed in μmol of Q10 per mg of protein.
Figure 2
Figure 2
(A) Mitochondrial mass levels of protein marker (VDAC) isolated from PBMC’s and referenced to total protein amount. (B) Selective autophagy levels of protein marker [LC3-lib] isolated from PBMC’s and referenced to total protein amount. (C) Mitochondrial generation and wear balance ratio referenced to total protein amount.
Figure 3
Figure 3
Mitochondrial balance ratio represented of patients with fibromyalgia before (white bars) and after (drawn bars) CoQ10 treatment. Green striped post-treatment bars represent positive ratios after CoQ10 treatment; red striped bars represent negative ratios after treatment; blue striped bar represent no ratio change after CoQ10 treatment.
Figure 4
Figure 4
FIQ values of patients before and after CoQ10 treatment.
Figure 5
Figure 5
Scheme showing the relationship among mitophagy, mitochondrial biogenesis and cell death.

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