Spinal signatures of entrenched and treated neuropathic pain

Spinal signatures of entrenched and treated neuropathic pain | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Spinal signatures of entrenched and treated neuropathic pain G Neely, Lipin Loo, Kazuma Fujikake, Sasha Saad, Teleri Clark, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4796294/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Chronic pain arises from an imbalance between excitation and inhibition. For chronic pain caused by peripheral nerve injury, sensory neuron damage leads to changes in spinal pain transduction, where enhanced excitatory and/or loss of inhibitory pathways can drive pain diseases. At the cellular level, the transcriptional changes occurring in entrenched chronic pain are largely unknown. Here we use single nuclei and spatial transcriptomic approaches to investigate the cellular and molecular causes of entrenched and treated neuropathic pain. Our data rules out a loss of spinal inhibitor neuron populations or transcriptional downregulation of inhibitory machinery, and instead we show that nerve injury leads to broad upregulation of spinal synaptic and excitatory pathways in dorsal neuronal and glial populations. We confirm these core populations are conserved in the human spinal cord, and show an effective pain therapy acts by dampening these neuropathic transcriptional programs. Overall, our data provides the first high resolution transcriptional analysis of the neuropathic spinal cord, highlighting known and novel pathways that may help us better manage pain diseases. Biological sciences/Molecular biology/Transcriptomics Biological sciences/Neuroscience/Diseases of the nervous system/Chronic pain Full Text Additional Declarations There is NO Competing Interest. All animal experiments were conducted under Animal Ethics Protocol 1646 issued and approved by the University of Sydney's Animal Ethics Committee. Supplementary Files SupplementalTable2Humandonordemographic.xlsx Supplemental Table 2 SupplementalTable1mSpinalCord300ggenelist.csv Supplemental Table 1 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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