A Molecular Signature of Myalgia in Myotonic Dystrophy 2.
BACKGROUND
Chronic muscle pain affects close to 20% of the population and is a major health burden. The underlying mechanisms of muscle pain are difficult to investigate as pain presents in patients with very diverse histories. Treatment options are therefore limited and not tailored to underlying mechanisms. To gain insight into the pathophysiology of myalgia we investigated a homogeneous group of patients suffering from myotonic dystrophy type 2 (DM2), a monogenic disorder presenting with myalgia in at least 50% of affected patients.


METHODS
After IRB approval we performed an observational cross-sectional cohort study and recruited 42 patients with genetically confirmed DM2 plus 20 healthy age and gender matched control subjects. All participants were subjected to an extensive sensory-testing protocol. In addition, RNA sequencing was performed from 12 muscle biopsy specimens obtained from DM2 patients.


RESULTS
Clinical sensory testing as well as RNA sequencing clearly separated DM2 myalgic from non-myalgia patients and also from healthy controls. In particular pressure pain thresholds were significantly lowered for all muscles tested in myalgic DM2 patients but were not significantly different between non-myalgic patients and healthy controls. The expression of fourteen muscle expressed genes in myalgic patients was significantly up or down-regulated in myalgic compared to non-myalgic DM2 patients.


CONCLUSIONS
Our data support the idea that molecular changes in the muscles of DM2 patients are associated with muscle pain. Further studies should address whether muscle-specific molecular pathways play a significant role in myalgia in order to facilitate the development of mechanism-based therapeutic strategies to treat musculoskeletal pain.


BACKGROUND
This study was funded by the German Research Society (DFG, GK1631), KAP programme of Charité Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine.
Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany; Dept. of Anesthesiology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Rabih
R
Moshourab
Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of the Charité University Medicine Berlin and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Vinko
V
Palada
Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of the Charité University Medicine Berlin and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Stefanie
S
Grunwald
Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of the Charité University Medicine Berlin and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Ulrike
U
Grieben
Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany. Electronic address: glewin@mdc-berlin.de.
Gary R
GR
Lewin
Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of the Charité University Medicine Berlin and the Max Delbrück Center for Molecular Medicine, Berlin, Germany. Electronic address: simone.spuler@charite.de.
Simone
S
Spuler
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D063806:Myalgia / Q000235:genetics*; D009223:Myotonic Dystrophy / Q000150:complications*; D017288:Pain Threshold; D017423:Sequence Analysis, RNA / Q000379:methods*
MAO B inhibitor; Myalgia; Myotonic dystrophy 2; Pressure pain threshold; Quantitative sensory testing; RNA Seq