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Papers of the Week

Papers: 20 Apr 2019 - 26 Apr 2019

Animal Studies

2019 Apr 24

Sci Rep



SMN deficiency causes pain hypersensitivity in a mild SMA mouse model through enhancing excitability of nociceptive dorsal root ganglion neurons.


Spinal muscular atrophy (SMA) is a devastating motor neuron degeneration disease caused by a deficiency of the SMN protein. Majority of patients also suffer from chronic pain. However, the pathogenesis of pain in the context of SMA has never been explored. In this study, using various pain tests, we found that a mild SMA mouse model presents with multiple forms of pain hypersensitivity. Patch-clamp recording showed that nociceptive neurons in SMA mouse dorsal root ganglia (DRGs) are hyperexcitable and their sodium current densities are markedly increased. Using quantitative RT-PCR, western blotting and immunofluorescence, we observed enhanced expression of two main voltage-gated sodium channels Na1.7 and Na1.8 in SMA mouse DRGs, which is at least in part due to increase in both expression and phosphorylation of NF-κB p50/p65 heterodimer. Moreover, we revealed that plasma norepinephrine levels are elevated in SMA mice, which contributes to mechanical hypersensitivity via the β2-adrenergic receptor. Finally, we uncovered that β2-adrenergic signaling positively modulates expression as well as phosphorylation of p50 and p65 in SMA mouse DRGs. Therefore, our data demonstrate that SMA mice, similar to humans, also develop pain hypersensitivity, and highlight a peripheral signaling cascade that elicits the mechanical sensitization in the mouse model, suggesting potential targets for therapeutic intervention.