Fibromyalgia syndrome: metabolic and autophagic processes in intermittent cold stress mice

Abstract

Fibromyalgia is characterized by widespread musculoskeletal pain, fatigue, and depression. The aim was to analyze potential mitochondrial dysfunction or autophagy in mice after exposure to intermittent cold stress (ICS). Muscle and liver specimens were obtained from 36 mice. Lactate dehydrogenase (LDH) activity was measured. Microtubule‐associated protein light chain 3 (MAP1LC3B) and glycogen content were determined histologically; muscle ultrastructure by electron microscopy. Mitochondrial‐ and autophagy‐related markers were analyzed by RT‐qPCR and Western blotting. ATP level, cytotoxicity, and caspase 3 activity were measured in murine C2C12 myoblasts after ICS exposure. Coenzyme Q10B (COQ10B) transcript was up‐regulated in limb muscle of ICS mice, whereas its protein content was stable. Cytochrome C oxidase 4 (COX4I1) and LDH activity increased in limb muscle of male ICS mice. Glycogen content was lower in muscle and liver tissue of male ICS mice. Electron micrographs of ICS mice specimens showed mitochondrial damage and autophagic vesicles. A significant up‐regulation of autophagic transcripts of MAP1LC3B and BECLIN 1 (BECN1) was observed. Map1lc3b protein showed an aggregated distribution in ICS mice and SqSTM1/p62 (p62) protein level was stable. Furthermore, ATP level and caspase activity, detected as apoptotic marker, were significantly lowered after ICS exposure in differentiated C2C12 myoblasts. The present study shows that ICS mice are characterized by mitochondrial dysfunction, autophagic processes, and metabolic alterations. Further investigations could dissect autophagy process in the proposed model and link these mechanisms to potential therapeutic options for fibromyalgia.

Adrenalectomy attenuates hyperalgesia but does not regulate muscle wasting in a female rat model of fibromyalgia

“…Our results using a hyperalgesic priming model are consistent with the muscle effects obtained in other experimental models of FM induced by depletion of biogenic amines 34,35 or intermittent cold stress. 7,36 In these studies, the authors observed not only muscle atrophy, but also an increase in the expression of atrogenes 34 and mitophagy, 36 as well as an imbalance in muscle antioxidant capacity. 34 These structural and metabolic disturbances could, at least partially, justify the changes in musculoskeletal functionality observed in FM patients.…”

Evaluation of Endothelial Dysfunction and Autophagy in Fibromyalgia-Related Vascular and Cerebral Cortical Changes and the Ameliorative Effect of Fisetin

“…The increased demonstrating the expression of the autophagy markers and the appearance of ultrastructure changes in the mitochondria, indicating marked autophagy of the mitochondria. It was reported that in early autophagosomes, the mitochondria are degraded in response to oxidative stress [ 46 ], making it a significant source of ROS, especially in conditions that are associated with mitochondrial damage and stress [ 49 ] such as in fibromyalgia [ 50 ]. The mitochondrial dysfunction in fibromyalgia agrees with the data published by Martínez-Lara et al, [ 9 ].…”

An Antioxidant Nanoparticle Enhances Exercise Performance in Rat High‐intensity Running Models

“…White mitochondria were assessed as damaged mitochondria, according to a previous study. [ 53 ]…”

“…White mitochondria were assessed as damaged mitochondria, according to a previous study. [53] Plasma Hemolysis Assay: Hemoglobin concentration was measured to determine hemolysis after high-intensity running and was measured by measuring the plasma absorbance at 380, 415, and 450 nm. [54] The iron content in the plasma was measured by inductively coupled plasma-mass spectrometry (ELAN DRC-e, Perkin Elmer, USA).…”