Comparison of the Levels of Pro-Inflammatory Cytokines Released in the Vastus Lateralis Muscle of Patients with Fibromyalgia and Healthy Controls during Contractions of the Quadriceps Muscle – A Microdialysis Study

Abstract

ObjectiveFibromyalgia is associated with central hyperexcitability, but it is suggested that peripheral input is important to maintain central hyperexcitability. The primary aim was to investigate the levels of pro-inflammatory cytokines released in the vastus lateralis muscle during repetitive dynamic contractions of the quadriceps muscle in patients with fibromyalgia and healthy controls. Secondarily, to investigate if the levels of pro-inflammatory cytokines were correlated with pain or fatigue during these repetitive dynamic contractions.Material and Methods32 women with fibromyalgia and 32 healthy women (controls) participated in a 4 hour microdialysis session, to sample IL-1β, IL-6, IL-8, and TNF from the most painful point of the vastus lateralis muscle before, during and after 20 minutes of repeated dynamic contractions. Pain (visual analogue scale; 0–100) and fatigue Borg’s Rating of Perceived Exertion Scale; 6–20) were assessed before and during the entire microdialysis session.ResultsThe repetitive dynamic contractions increased pain in the patients with fibromyalgia (P < .001) and induced fatigue in both groups (P < .001). Perceived fatigue was significantly higher among patients with fibromyalgia than controls (P < .001). The levels of IL-1β did not change during contractions in either group. The levels of TNF did not change during contractions in patients with fibromyalgia, but increased in controls (P < .001) and were significantly higher compared to patients with fibromyalgia (P = .033). The levels of IL-6 and IL-8 increased in both groups alike during and after contractions (P’s < .001). There were no correlations between pain or fatigue and cytokine levels after contractions.ConclusionThere were no differences between patients with fibromyalgia and controls in release of pro-inflammatory cytokines, and no correlations between levels of pro-inflammatory cytokines and pain or fatigue. Thus, this study indicates that IL-1β, IL-6, IL-8, and TNF do not seem to play an important role in maintenance of muscle pain in fibromyalgia.

Altered Inflammatory Mediators in Fibromyalgia

“…However, unlike the variability of results found in the blood of FM patients regarding IL-8 concentration, in the cerebrospinal fluid of these patients, it has only been found high concentrations of IL-8, a cytokine which promoving and mediating the pain [106,107]. As with other pro-inflammatory cytokines, we have not found reported differences in the concentration of IL-8 either on the muscle or on the skin of patients with FM [108,109]. IL-18, inflammatory cytokine closely related to the inflammasome function, was found elevated in the serum of patients with FM [83].…”

“…However, no differences were found in concentrations of TNF-α in skin of people with FM [108] or in muscle [109]. Although a recent study conducted by SanchezDominguez et al [35] have detected higher concentrations of TNFαin saliva and in the skin of FM patients when compared to healthy women.…”

“…However, recent studies have reported high levels of IL-6 in FM patients [98,103,104]. While there are no differences in the concentrations of IL-6 either on the skin [108] or on the muscle [109] of FM patients compared to healthy people.…”

“…However, recent studies have reported high levels of IL-6 in FM patients [98,103,104]. While there are no differences in the concentrations of IL-6 either on the skin [108] or on the muscle [109] of FM patients compared to healthy people.IL-8, a pro-inflammatory cytokine and chemokine (CXCL8), is a potent chemoatractant of neutrophils [94] (essential cells for the development of the inflammatory response, and is also a potent promoter of sympathetic pain [53,94]. The IL-8 has been found to be elevated in both serum and plasma of patients with FM [10,53,91,[97][98][99]100,106,107,111,113].…”

Endocannabinoids and Related Lipids in Chronic Pain: Analytical and Clinical Aspects

“…This result is not in line with other reports. For example, Wang et al found elevated levels of circulating TNF-α in FM, but no correlation between these levels and pain intensity [164], and Christidis et al did not find any difference between plasma levels of TNF-α between FM and controls and or any correlation with pain intensity [165]. In addition, more recently Ohgidani et al reported that protein levels and the expression of TNF-α at mRNA level significantly increased ATP-stimulated induced microglia-like cells in patients with FM compared healthy controls.…”