A Molecular Signature of Myalgia in Myotonic Dystrophy 2

• Pressure pain thresholds were reduced in myotonic dystrophy 2 (DM2) and myalgias, but not in DM2 without myalgias
• RNASeq from skeletal muscle differed significantly in 14 genes between DM2 with myalgias and DM2 without myalgiasPatients with a rare type of muscle dystrophy (myotonic dystrophy type 2) that is caused by a single genetic mutation usually suffer from muscle weakness and wasting but a majority also suffer from chronic muscle pain in their extremities. In our study, we found that these patients are sensitive to pressure stimuli over muscles that are not usually perceived as painful. We also identified several muscle genes that might highlight a molecular link to muscle pain. These findings call for further research to learn how and whether the genetic impairments in muscle contribute to muscle pain.

BackgroundChronic 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.MethodsAfter 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.FindingsClinical 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.InterpretationOur 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.FundingThis study was funded by the German Research Society (DFG, GK1631), KAP programme of Charité Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine.