Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms

Kaplan, Chelsea M.; Kelleher, Eoin; Irani, Anushka; Schrepf, Andrew; Clauw, Daniel J.; Harte, Steven E.

doi:10.1038/s41582-024-00966-8

Cited by 15 publications

(1 citation statement)

References 284 publications

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“…Nociplastic pain presents as multifocal pain without discernable tissue or nerve damage, alongside central nervous system comorbidities such as fatigue, sleep disturbances, and mood disorders. Although the mechanisms of nociplastic pain are not completely understood, it is thought that augmented central sensitization and pain modulation are key contributors ( Fitzcharles et al , 2021 ; Kaplan et al , 2024 ). Among the three types of pain, myotonia-induced pain best represents a form of nociplastic pain or pain phenotype that arises from altered nociception in the absence of tissue damage.…”

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

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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.

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Section: Discussionmentioning

confidence: 99%