Melatonin, an antioxidant, may be beneficial in treating imbalances in the mitochondria of people with fibromyalgia, a complication known as mitochondrial dysfunction, a study in rats with fibromyalgia-like chronic pain symptoms reports.
The study, “Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin,” was published in the International Journal of Molecular Sciences.
Fibromyalgia is a chronic musculoskeletal pain disorder, with an unknown cause. It has been suggested that this syndrome is linked to problems in the workings of mitochondria — the powerhouses of the cell, responsible for providing energy.
Mitochondrial dysfunction also leads to oxidative stress, an imbalance between the production of toxic molecules called free radicals and the body’s ability to counteract them, which has also been implicated in the development of fibromyalgia.
However, the link between mitochondrial dysfunction, oxidative stress and fibromyalgia is still unclear. Therefore, researchers set out to determine the role of three different mitochondrial proteins — peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1α), mitofusin2 (Mfn2), and coenzyme Q10 (CoQ10) — in this disease.
PGC-1α is a protein that stimulates mitochondrial biogenesis (production) in cells, Mfn2 helps determine the shape and structure of mitochondria, and CoQ10 is an essential component of the energy-producing machinery in the mitochondria as well as an important antioxidant (molecule that counteracts oxidative stress).
Researchers used a rat model of fibromyalgia, called the reserpine-induced myalgic (RIM) rats. Prior studies have shown that RIM rats are less active and gave lower body weight, with a significant aversion to eating, than other rats. Similar symptoms are consistently seen in fibromyalgia patients.
First, they established that RIM rats were indeed a good model for studying fibromyalgia by showing that their voluntary motor activity (locomotion activity) was significantly less than that of healthy rats. Specifically, they showed that the RIM rats ran a shorter distance and at slower speeds.
Next, the researchers assessed the role of melatonin in treating RIM rats, as prior studies have shown that levels of melatonin and its precursors are low in fibromyalgia patients, affecting both sleep and perception. Previous studies in animal models and patients also suggested that melatonin supplements might ease symptoms.
Results indicated that RIM rats treated with melatonin significantly improved their voluntary motor activity, increasing both the distance ran and speed of running to levels that similar to healthy rats.
Researchers also observed that RIM rats had significant skeletal muscle atrophy (loss), with a smaller diameter in the gastrocnemius myotubes (calf muscle) compared to healthy rats. Melatonin treatment restored the gastrocnemius myotubes of the RIM group to diameters found in the control animals.
Initial expression of PGC-1α in the gastrocnemius was also almost null in the RIM rats but moderately expressed in the healthy rats. Mfn2 expression in the gastrocnemius of RIM group was weak while strongly expressed in healthy rats.
Treatment with melatonin increased levels of both PGC-1α and Mfn2 in the RIM group.
As there is a known correlation between Mfn2 depletion and CoQ10 reduction, researchers found that levels of CoQ10 were also lower in the RIM group compared to healthy rats. Again, melatonin treatment led to an increase in CoQ10 levels in RIM rats treated with melatonin.
“Herein, we demonstrated that: (1) RIM rats are a good model for evaluating the etiogenesis [cause] of FMS; (2) mitochondrial dysfunction and the oxidative stress mediated by PGC-1α, Mfn2 and CoQ10 are involved in the FSM [fibromyalgia syndrome] outcome; (3) melatonin is useful to improve mitochondrial performance,” the researchers wrote.
“Mitochondria targeted antioxidants such as melatonin can be of scientific interest, and they should be taken in consideration for improving mitochondria health and/or mitochondrial related diseases,” they concluded.