H Sprott1, S Salemi, R E Gay, L A Bradley, G S Alarcón, S J Oh, B A Michel, S Gay. 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. haiko.sprott@usz.ch
Abstract
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.
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.
Authors: Keijo Häkkinen; Arto Pakarinen; Pekka Hannonen; Arja Häkkinen; Olavi Airaksinen; Heli Valkeinen; Markku Alen Journal: J Rheumatol Date: 2002-06 Impact factor: 4.666
Authors: Leonard A Jason; Karina Corradi; Susan Torres-Harding; Renee R Taylor; Caroline King Journal: Neuropsychol Rev Date: 2005-03 Impact factor: 7.444
Authors: C Sommer; W Häuser; K Gerhold; P Joraschky; F Petzke; T Tölle; N Uçeyler; A Winkelmann; K Thieme Journal: Schmerz Date: 2008-06 Impact factor: 1.107
Authors: Eli Iacob; Alan R Light; Gary W Donaldson; Akiko Okifuji; Ronald W Hughen; Andrea T White; Kathleen C Light Journal: Arthritis Care Res (Hoboken) Date: 2016-01 Impact factor: 4.794
Authors: Ratchakrit Srikuea; T Brock Symons; Douglas E Long; Jonah D Lee; Yu Shang; Peter J Chomentowski; Guoqiang Yu; Leslie J Crofford; Charlotte A Peterson Journal: Arthritis Rheum Date: 2013-02
Authors: Jinong Feng; Zhifang Zhang; Wenyan Li; Xiaoming Shen; Wenjia Song; Chunmei Yang; Frances Chang; Jeffrey Longmate; Claudia Marek; R Paul St Amand; Theodore G Krontiris; John E Shively; Steve S Sommer Journal: PLoS One Date: 2009-12-30 Impact factor: 3.240
Authors: Mario D Cordero; Manuel De Miguel; Ana M Moreno Fernández; Inés M Carmona López; Juan Garrido Maraver; David Cotán; Lourdes Gómez Izquierdo; Pablo Bonal; Francisco Campa; Pedro Bullon; Plácido Navas; José A Sánchez Alcázar Journal: Arthritis Res Ther Date: 2010-01-28 Impact factor: 5.156