Assessment of small sensory fiber function in myotonic dystrophy type 1

Boland-Freitas, Robert; Ng, Karl

doi:10.1002/mus.26673

Cited by 4 publications

(2 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, our ex vivo electrophysiology and calcium imaging data suggest that peripheral sensitization is likely not responsible for the pain-like behavior. While rigorous quantitative sensory testing in myotonic patients has remained limited, our preclinical data aligns with multiple studies that have demonstrated limited peripheral sensory neuron abnormalities in myotonic dystrophy patients (Hermans et al ., 2011; Peric et al ., 2013; Nojszewska et al ., 2015; Boland-Freitas & Ng, 2019). Nevertheless, we cannot rule out peripheral involvement as an initial priming event for central sensitization.…”

Section: Discussionmentioning

confidence: 99%

Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors

Nelson,

Duran,

Calderon-Rivera

et al. 2024

Preprint

View full text Add to dashboard Cite

Pain is a prominent and debilitating symptom in myotonic disorders, yet its physiological mechanisms remain poorly understood. This study assessed preclinical pain-like behavior in murine models of pharmacologically induced myotonia and myotonic dystrophy type 1 (DM1). In both myotonia congenita and DM1, impairment of theCLCN1gene, which encodes skeletal muscle voltage-gated CLC-1 chloride channels, reduces chloride ion conductance in skeletal muscle cells, leading to prolonged muscle excitability and delayed relaxation after contraction. We used the CLC-1 antagonist anthracene-9- carboxylic acid (9-AC) at intraperitoneal doses of 30 or 60 mg/kg and HSA LR20b DM1 mice to model CLC-1-induced myotonia. Our experimental approach includedin vivopain behavioral testing,ex vivocalcium imaging, and whole-cell current-clamp electrophysiology in mouse dorsal root ganglion (DRG) neurons. A single injection of 9-AC induced myotonia in mice, which persisted for several hours and resulted in long-lasting allodynic pain-like behavior. Similarly, HSA LR20b mice exhibited both allodynia and hyperalgesia. Despite these pain-like behaviors, DRG neurons did not show signs of hyperexcitability in either myotonic model. These findings suggest that myotonia induces nociplastic pain-like behavior in preclinical rodents, likely through central sensitization mechanisms rather than peripheral sensitization. This study provides insights into the pathophysiology of pain in myotonic disorders and highlights the potential of using myotonic mouse models to explore pain mechanisms and assess novel analgesics. Future research should focus on the central mechanisms involved in myotonia-induced pain and develop targeted therapies to alleviate this significant clinical burden.

show abstract

Section: Discussionmentioning

confidence: 99%

Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors

Nelson,

Duran,

Calderon-Rivera

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Some studies have shown that DM1 may involve the peripheral nervous system ( 2 – 4 ). Recently Boland-Freitas and Ng found indications of a subclinical small fiber neuropathy measured by quantitative sensory testing in patients with DM1 ( 5 ). Chronic pain has been reported in about 60%, and has been associated with fatigue, reduced motor function and quality of life ( 6 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

Small and large fiber neuropathy in adults with myotonic dystrophy type 1

Solbakken,

Løseth,

Frich

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

IntroductionMyotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder that affects multiple organs. In this study, we investigated symptoms of pain and presence of small and large fiber neuropathy in the juvenile and adult form of DM1.MethodTwenty genetically verified DM1 patients were included. Pain was assessed, and neurological examination and investigations of the peripheral nervous system by quantification of small nerve fibers in skin biopsy, quantitative sensory testing and nerve conduction studies were performed. Results from skin biopsies were compared to healthy controls.ResultSeventeen patients reported chronic pain. Large and/or small fiber abnormalities were present in 50% of the patients. The intraepidermal nerve fiber density was significantly lower in the whole group of patients compared to healthy controls.ConclusionSmall-fiber neuropathy might be an important cause of pain in DM1.

show abstract

Systemic Complications of Muscular Dystrophies

Kassardjian,

Liewluck

2023

Current Clinical Neurology

View full text Add to dashboard Cite

Assessment of small sensory fiber function in myotonic dystrophy type 1

Cited by 4 publications

References 16 publications

Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors

Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors

Small and large fiber neuropathy in adults with myotonic dystrophy type 1

Systemic Complications of Muscular Dystrophies

Contact Info

Product

Resources

About