Is Inflammation a Mitochondrial Dysfunction-Dependent Event in Fibromyalgia?

Abstract

Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide. Both mitochondrial dysfunction and inflammation have been implicated in the pathophysiology of FM. We have investigated the possible relationship between mitochondrial dysfunction, oxidative stress, and inflammation in FM. We studied 30 women diagnosed with FM and 20 healthy women. Blood mononuclear cells (BMCs) from FM patients showed reduced level of coenzyme Q₁₀ (CoQ₁₀) and mtDNA contents and high level of mitochondrial reactive oxygen species (ROS) and serum tumor necrosis factor (TNF)-alpha and transcript levels. A significant negative correlation between CoQ₁₀ and TNF-alpha levels (r=-0.588; p<0.01), and a positive correlation between ROS and TNF-alpha levels (r=0.791; p<0.001) were observed accompanied by a significant correlation of visual analogical scale with serum TNF-alpha and transcript levels (r=0.4507; p<0.05 and r=0.7089; p<0.001, respectively). TNF-alpha release was observed in an in vitro (BMCs) and in vivo (mice) CoQ₁₀ deficiency model. Oral CoQ₁₀ supplementation restored biochemical parameters and induced a significant improvement in clinical symptoms (p<0.001). These results lead to the hypothesis that inflammation could be a mitochondrial dysfunction-dependent event implicated in the pathophysiology of FM in several patients indicating at mitochondria as a possible new therapeutic target.

Fibromyalgia: A Critical and Comprehensive Review

“…However, there are indications that mitochondrial dysfunction induced by CoQ10 deficiency is associated with inflammasome activation and production of IL-1β and IL-18 both in vitro and in vivo, including higher serum levels of both of these cytokines in FMS patients compared to healthy controls [435]. Serum TNFα concentrations were also elevated and the levels of IL-1β and TNFα correlated with pain scores [418]. The concentrations of CoQ10 in PBMC closely parallel those in skeletal muscle [499].…”

“…Instead, the available data are highly heterogeneous. For example, higher, lower, or similar group mean concentrations of IL-1β, IL-6, and TNFα have been reported in FMS patients compared to healthy controls [340,[416][417][418][419][420][421][422][423][424]. Fewer studies have addressed the peripheral levels of Th2 or anti-inflammatory cytokines, but the results have also been quite varied, with mean serum or plasma levels of IL-4, IL-5, and IL-10 being increased, decreased, or not significantly different between FMS patients and healthy controls [416,417,[425][426][427].…”

“…The most consistent finding is a positive association of circulating IL-8 concentrations with pain intensity [431][432][433], although the association was found to be inverse rather than direct in another study [434]. Other cytokines positively associated with pain intensity are IL-1β [435], TNFα [418], and IL-6 [425], but again there are data suggesting a negative correlation at least in post-menopausal women, whereas no association was evident in pre-menopausal women [433]. IL-1β, IL-6, TNFα and MCP-1 are quite consistently associated with MDD [436,437], but studies in FMS patients have failed to detect a correlation between depression ratings and IL-6 [420,422] or other cytokines [427], whereas IL-5 showed a negative relationship [420].…”

Fibromyalgia Syndrome in Need of Effective Treatments

“…In particular, patients with FMS demonstrated higher serum prolidase activity, total oxidative status, and oxidative stress index than healthy controls, and serum prolidase activity positively correlated with pain and fatigue scores (Bozkurt et al, 2014). Moreover, PBMCs from FMS patients showed reduced levels of coenzyme Q 10 (CoQ 10 ) and mtDNA contents, but high levels of mt reactive oxygen species and serum TNF (Cordero et al, 2013). Oxidative stress is present during tissue inflammation and also triggers MCs (Frossi et al, 2003).…”

LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection

“…Recent studies have revealed that mitochondrial dysfunction plays a key role in the inflammatory response (Cordero et al, 2013;Joven, 2013). To investigate the effect of LL-37 on mitochondrial function, the protein levels of peroxisome proliferator-activated receptor gamma coactivator-1 ␣ (PGC-1␣), the key regulator of mitochondrial biogenesis, and mitochondrial respiratory chain enzyme complexes were determined in LL-37 overexpressing and knockdown cells.…”