Translational control in the spinal cord regulates gene expression and pain hypersensitivity in the chronic phase of neuropathic pain
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Abstract
Sensitization of spinal nociceptive circuits plays a crucial role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that, in mice, changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell type-specific profiling revealed that spinal inhibitory and excitatory neurons exhibited substantial changes in translation after peripheral nerve injury. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV + ) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV + neurons decreased their intrinsic excitability and spiking activity. Conversely, reducing translation in spinal PV + neurons prevented the nerve injury-induced decrease in excitability but did not alleviate mechanical hypersensitivity. Together, these findings advance our understanding of translational control mechanisms in the spinal cord during neuropathic pain and highlight their cell type- and phase-specific contributions to gene expression and pain hypersensitivity.
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Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
Taniguchi, Y., Choi, P. J., Li, G.-W., Chen, H., Babu, M., Hearn, J., Emili, A., & Xie, X. S. (2010) · Science · doi:10.1126/science.1188308 · Cited by 1,982 · see citing works
Autism-related deficits via dysregulated eIF4E-dependent translational control
Gkogkas, C. G., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D. B., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., et al. (2013) · Nature · doi:10.1038/nature11628 · Cited by 522 · see citing works
Self-citationCell type–specific mRNA purification by translating ribosome affinity purification (TRAP)
Heiman, M., Kulicke, R., Fenster, R. J., Greengard, P., & Heintz, N. (2014) · Nature Protocols · doi:10.1038/nprot.2014.085 · Cited by 498 · see citing works
Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
Petitjean, H., Pawlowski, S. A., Fraine, S. L., Sharif, B., Hamad, D., Fatima, T., Berg, J., Brown, C. M., Jan, L.-Y., Ribeiro-da-Silva, A., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.080 · Cited by 326 · see citing works
Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury
Peirs, C., Williams, S.-P. G., Zhao, X., Arokiaraj, C. M., Ferreira, D. W., Noh, M.-C., Smith, K. M., Halder, P., Corrigan, K. A., Gedeon, J. Y., et al. (2021) · Neuron · doi:10.1016/j.neuron.2020.10.027 · Cited by 190 · see citing works
Antidepressant actions of ketamine engage cell-specific translation via eIF4E
Aguilar-Valles, A., De Gregorio, D., Matta-Camacho, E., Eslamizade, M. J., Khlaifia, A., Skaleka, A., Lopez-Canul, M., Torres-Berrio, A., Bermudez, S., Rurak, G. M., et al. (2021) · Nature · doi:10.1038/s41586-020-03047-0 · Cited by 144 · see citing works
Self-citationBoyle, K. A., Gradwell, M. A., Yasaka, T., Dickie, A. C., Polgár, E., Ganley, R. P., Orr, D. P. H., Watanabe, M., Abraira, V. E., Kuehn, E. D., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.040 · Cited by 131 · see citing works
A spinoparabrachial circuit defined by Tacr1 expression drives pain
Barik, A., Sathyamurthy, A., Thompson, J., Seltzer, M., Levine, A., & Chesler, A. (2021) · eLife · doi:10.7554/elife.61135 · Cited by 93 · see citing works
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- Authors
- Lister, K. C., Wong, C., Uttam, S., Parisien, M., Stecum, P., Brown, N., Cai, W., Ho-Tieng, D., Hooshmandi, M., Gu, N., Amiri, M., Beaudry, F., Jafarnejad, S. M., Tavares-Ferreira, D., Inturi, N. N., Mazhar, K., Zhao, H. T., Fitzsimmons, B., Gkogkas, C. G., Sonenberg, N., Price, T. J., Diatchenko, L., Atlasi, Y., Mogil, J. S., & Khoutorsky, A.
- Affiliations
- McGill University (CA)
- Queen's University Belfast (GB)
- Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas
- The University of Texas at Dallas (US)
- Ionis Pharmaceuticals (United States) (US)
- Corresponding author
- Khoutorsky, Arkady
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2026-04-10
- Volume
- 13
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC13068433
- OpenAlex
- W4402592848
- Cited by
- 2
- References
- 9
- Citations by year
- 2026: 1 · 2025: 1
- Type
- posted content
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Institutes of Health Research (PJT-870 162412, FRN-154281)
- NIH NINDS (NS065926)
- General Secretariat for Research and Innovation Greece (Τ12ΕΡΑ5-00024)
- Louise and Alan Edwards Foundation PhD fellowship
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- translational regulation, neuropathic pain, chronic pain, spinal cord, hyperalgesia, parvalbumin interneurons, inhibitory neurons, excitatory neurons, peripheral nerve injury, intrinsic excitability, mechanical hypersensitivity, nociceptive circuits, gene expression regulation
- MeSH terms
- Animals, Gene Expression Regulation, Hyperalgesia, Male, Mice, Inbred C57BL, Neuralgia, Neurons, Spinal Cord, Protein Biosynthesis, Mice, Peripheral Nerve Injuries
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