Research ArticlePain

Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice

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Science Translational Medicine  10 Mar 2021:
Vol. 13, Issue 584, eaay9056
DOI: 10.1126/scitranslmed.aay9056

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  • RE: Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice
    • Rasheen Powell, PhD Candidate, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo

    The authors have presented a novel method for treating pain in a variety of pain models using an impressive genetic repression approach. However, there are some concerning oversights that obscure the conclusion drawn due to a lack of exhaustive experimental design which we believe limits the potential translatability of this method and required comment. First, it appears only male animals are used in this manuscript. Biological relevance and clinical translatability can only be truly considered if male and female animals are included. In fact, in an effort to increase rigor and reproducibility, the NIH has made it a requirement to consider potential sex differences(1). There is an ever-growing body of literature that supports the idea that male and female nociception differs from both neurobiological and pathophysiological standpoints (2,3,4). Secondly, while the authors show that lumbar injection of the AAV9-mCherry results in transduction of DRG neurons distal from the site of injection with increasing viral titer, they do not indicate what effect their intrathecal delivery method has on NaV1.7 transcript levels in the spinal cord despite NaV1.7 having been shown to be expressed in deep lamina within the dorsal horn (5). We believe that this obscures the role of the DRGs in this context. Further, the authors solely utilize qPCR and RNAscope as methods to validate knockdown of NaV1.7. Although these approaches are exhaustive in scope, demonstrating protein expression cha...

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    Competing Interests: None declared.

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