Mitochondrial function in patients affected with fibromyalgia syndrome is impaired and correlates with disease severity

Abstract

Fibromyalgia is a musculoskeletal syndrome characterized by chronic widespread pain that is often associated with systemic manifestations. Since mitochondria are the main source of cellular energy, we hypothesized that fibromyalgia syndrome (FMS) could be linked to mitochondrial impairment. Aim was to study mitochondrial dysfunction in peripheral blood mononuclear cells isolated from 50 patients with primary FMS and 20 apparently healthy controls. Although no differences in mitochondrial basal respiration were observed between patients with primary FMS and healthy controls, a lower median bioenergetic health index (BHI; - 22.1%, p = 0.03), a proxy of mitochondrial function, was found in patients. According to fibromyalgia severity score (FSS), a composite of widespread pain index and symptom severity scale, a lower median BHI (- 18.7%) was found in patients with a FSS ≥ 20 compared to those with a FSS < 20. Negative moderate correlations were found only between BHI and FSS (r = - 0.36) and widespread pain index (r = - 0.38). We demonstrated that patients with FMS had an impaired mitochondrial function. Additionally, we found a mild correlation between the widespread pain index and the BHI, possibly indicating that the altered mitochondrial function, in these patients, narrows musculoskeletal rather than central nervous system involvement.

Fig. 1

Evaluation of mitochondrial functionality in PBMC of controls and patients with fibromyalgia syndrome (FMS). Panel A) shows the oxygen consumption rate (OCR) measured through the Seahorse XF Cell Mito Stress Test. Panel B) shows maximal respiration. Panel C) shows the spare respiratory capacity (as expressed in %) and panel D) the distribution of the BHI. Light grey line and bars represent the control group (n = 20), and dark grey line and bars represent patients with FMS (n = 50). Yellow dots represent patients with FSS score < 20, while red dots represent patients with FSS score ≥ 20. Results are expressed as median (Q1, Q3). Differences between groups were assessed by Mann–Whitney U test, *p < 0.05. AA, Antimycin A; BHI, Bioenergetic Health Index; FCCP Carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone; FMS, Fibromyalgia patients; FSS, Fibromyalgia Severity Score; OCR, Oxygen Consumption Rate; PBMC, peripheral blood mononuclear cells; Rot, rotenone.

Fig. 2

Evaluation of mitochondrial functionality in peripheral blood mononuclear cells (PBMC) of patients with fibromyalgia syndrome and a FSS < 20 (n = 18) and in the group with FSS ≥ 20 (n = 32). Panel A) shows the oxygen consumption rate (OCR) measured through the Seahorse XF Cell Mito Stress Test. Panel B) indicates the spare respiratory capacity (as expressed in %) and Panel C) the distribution of BHI. Orange bars represent the group with FSS < 20 and red bars represent the FSS ≥ 20 group. Results are expressed as median (Q1, Q3). Differences between groups were by Mann–Whitney U test, *p < 0.05; **p < 0.01. AA Antimycin A; BHI, Bioenergetic Health Index; FCCP Carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone; FSS, Fibromyalgia Severity Score; OCR, Oxygen Consumption Rate; PBMCS, peripheral blood mononuclear cells; Rot, rotenone.

Fig. 3

Correlation analysis between the bioenergetic health index (BHI) vs total fibromyalgia severity score (FSS) (panel A); and vs widespread pain index (panel B). BHI, bioenergetic health index; WPI, widespread pain index.