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Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle fibres

H Sprott¹, S Salemi¹, R E Gay¹, L A Bradley², G S Alarcón², S J Oh³, B A Michel¹, S Gay¹

¹ WHO Collaborating Centre for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, Department of Rheumatology and Institute of Physical Medicine, University Hospital, Gloriastrasse 25, CH-8091 Zürich, Switzerland
² University of Alabama at Birmingham, Division of Clinical Immunology and Rheumatology, Birmingham, AL 35294, USA
³ University of Alabama at Birmingham, Department of Neurology, Birmingham, AL 35294, USA

Correspondence to:
Correspondence to:
Dr H Sprott
Centre of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital, Gloriastrasse 25, CH-8091 Zürich, Switzerland; haiko.sprott{at}usz.ch

Objective: To determine whether there is evidence of increased DNA fragmentation and ultrastructural changes in muscle tissue of patients with fibromyalgia (FM) compared with healthy controls.

Methods: Muscle tissues from 10 community residents with FM and 10 age and sex matched healthy controls were examined "blindly" for the presence of DNA fragmentation by two different methods: terminal deoxynucleotidyl transferase (TdT) staining (TUNEL) and the FragEL-Klenow DNA fragmentation detection kit. Ultrastructural analysis of tissue was performed by electron microscopy.

Results: DNA fragmentation was detected by both methods in 55.4 (SEM 2.5)% of the nuclei in muscle tissue of patients with FM compared with 16.1 (4.1)% (p<0.001) of the nuclei in healthy controls. Contrary to expectation, no typical features of apoptosis could be detected by electron microscopy. The myofibres and actin filaments were disorganised and lipofuscin bodies were seen; glycogen and lipid accumulation were also found. The number of mitochondria was significantly lower in patients with FM than in controls and seemed to be morphologically altered.

Conclusion: The ultrastructural changes described suggest that patients with FM are characterised by abnormalities in muscle tissue that include increased DNA fragmentation and changes in the number and size of mitochondria. These cellular changes are not signs of apoptosis. Persistent focal contractions in muscle may contribute to ultrastructural tissue abnormalities as well as to the induction and/or chronicity of nociceptive transmission from muscle to the central nervous system.

Keywords: fibromyalgia; DNA fragmentation; ultrastructure; electron microscopy; mitochondria

Abbreviations: ACR, American College of Rheumatology; CNS, central nervous system; DAB, 3,3'-diaminobenzidine; EMG, electromyographic; FM, fibromyalgia; NO, nitric oxide; TBS, Tris buffered saline; TdT, terminal deoxynucleotidyl transferase

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