Conserved transcriptional programming across sex and species after peripheral nerve injury predicts treatments for neuropathic pain Article Swipe
Shahrzad Ghazisaeidi
,
Milind M. Muley
,
YuShan Tu
,
Mahshad Kolahdouzan
,
Ameet S. Sengar
,
Arun Ramani
,
Michael Brudno
,
Michael Salter
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.22541/au.166325658.84625800/v1
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.22541/au.166325658.84625800/v1
Background and Purpose: Chronic pain is a devastating problem affecting 1 in 5 individuals around the globe, with neuropathic pain the most debilitating and poorly treated type of chronic pain. Advances in transcriptomics and data mining have contributed to cataloging diverse cellular pathways and transcriptomic alterations in response to peripheral nerve injury but have focused on phenomenology and classifying transcriptomic responses. Experimental approach: Here, with the goal of identifying new types of pain-relieving agents, we compared transcriptional reprogramming changes in the dorsal spinal cord after peripheral nerve injury cross-sex and cross-species and imputed commonalities, as well as differences in cellular pathways and gene regulation. Key Results : We identified 93 transcripts in the dorsal horn that were increased by peripheral nerve injury in male and female mice and rats. Following gene ontology and transcription factor analyses, we constructed a pain interactome for the proteins encoded by the differentially expressed genes, discovering new, conserved signaling nodes. We interrogated the interactome with the Drug-Gene database to predict FDA-approved medications that may modulate key nodes within the network. The top hit from the analysis was fostamatinib, the molecular target of which is the non-receptor tyrosine kinase Syk, which our analysis had identified as a key node in the interactome. Conclusions & Implications : We found that intrathecally administrating the active metabolite of fostamatinib, R406, significantly reversed pain hypersensitivity in both sexes. Thus, we have identified and shown the efficacy of an agent that could not have been previously predicted to have analgesic properties.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.22541/au.166325658.84625800/v1
- https://www.authorea.com/doi/pdf/10.22541/au.166325658.84625800
- OA Status
- gold
- Cited By
- 2
- References
- 42
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4296087874
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4296087874Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.22541/au.166325658.84625800/v1Digital Object Identifier
- Title
-
Conserved transcriptional programming across sex and species after peripheral nerve injury predicts treatments for neuropathic painWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-09-15Full publication date if available
- Authors
-
Shahrzad Ghazisaeidi, Milind M. Muley, YuShan Tu, Mahshad Kolahdouzan, Ameet S. Sengar, Arun Ramani, Michael Brudno, Michael SalterList of authors in order
- Landing page
-
https://doi.org/10.22541/au.166325658.84625800/v1Publisher landing page
- PDF URL
-
https://www.authorea.com/doi/pdf/10.22541/au.166325658.84625800Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.authorea.com/doi/pdf/10.22541/au.166325658.84625800Direct OA link when available
- Concepts
-
Interactome, Transcriptome, Neuropathic pain, Chronic pain, Nerve injury, Medicine, Bioinformatics, Biology, Neuroscience, Gene, Computational biology, Pharmacology, Genetics, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
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2023: 2Per-year citation counts (last 5 years)
- References (count)
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42Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.administrating | 214 |
| abstract_inverted_index.commonalities, | 93 |
| abstract_inverted_index.differentially | 147 |
| abstract_inverted_index.pain-relieving | 72 |
| abstract_inverted_index.transcriptomic | 44, 59 |
| abstract_inverted_index.transcriptional | 76 |
| abstract_inverted_index.transcriptomics | 32 |
| abstract_inverted_index.hypersensitivity | 224 |
| cited_by_percentile_year.max | 96 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5063628893 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 8 |
| corresponding_institution_ids | https://openalex.org/I185261750, https://openalex.org/I2800129641, https://openalex.org/I2801317318, https://openalex.org/I4210141030, https://openalex.org/I45129253 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7200000286102295 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.54813261 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |