Clinical and molecular profiling of muscle pain in myotonic dystrophy type 2 (S10.002)

2015 
OBJECTIVE: To unravel the molecular mechanisms of muscle pain in patients with myotonic dystrophy type 2 (DM2). BACKGROUND: Myalgias are very common, poorly understood and probably caused by a variety of factors. DM2 is a genetically defined muscle disorder due to expansion of CCTG repeats in intron 1 of ZNF9. Patients frequently complain about myalgias. Transcription of the expanded transcripts leads to missplicing of several effector genes and potentially could affect the nociception. We hypothesized that a common mechanism might underlie DM2-related myalgias. DESIGN/METHODS: In a case-control study we performed quantitative sensory testing (QST) in 29 DM2 patients (13 males and 16 female; 19 with and 10 without myalgia) and healthy controls, muscle microdialysis and RNA sequencing of 12 skeletal muscle biopsy specimens (from 6 patients with myalgias and 6 without myalgias). Pathway analysis of RNAseq data was performed with IPA® and GOrilla. The proteome and metabolome of the dialysate will be analysed. RESULTS: We found significant decrease in pressure pain thresholds in DM2 patients with myalgia compared to pain-free patients (p=0.027, Mann-Whitney Test). Moreover, patients with myalgia had a significant decrease in pain thresholds for cold (p=0.03, 2-Factor ANOVA) and heat (p=0.02, 2-Factor ANOVA) as well as increased mechanical pain sensitivity (p=0.025, 2-Factor ANOVA) compared to pain-free DM2. Wind-up ratios had a tendency to increase (p=0.08, 2-Factor ANOVA) in patients with myalgia. Furthermore, RNAseq data indicated significant differences in the gene expression between DM2 patients with and without pain related to the sensory perception, extracellular signalling and cellular response to the hormone stimulus. CONCLUSIONS: Our data show that DM2 related myalgias are primarily of muscular origin but some patients also develop additional central pain. The results may also help to understand other more common reasons for muscle pain such as fibromyalgia. Study Supported by: DFG GK 1631 Disclosure: Dr. Palada has nothing to disclose. Dr. Moshourab has nothing to disclose. Dr. Kempa has nothing to disclose. Dr. Boschmann has nothing to disclose. Dr. Lewin has nothing to disclose. Dr. Spuler has nothing to disclose.
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