title: Dendritic spine remodeling following early and late Rac1 inhibition after spinal cord injury: evidence for a pain biomarker.
abstract: Neuropathic pain is a significant complication following spinal cord injury (SCI) with few effective treatments. Drug development for neuropathic pain often fails because preclinical studies do not always translate well to clinical conditions. Identification of biological characteristics predictive of disease state or drug responsiveness could facilitate more effective clinical translation. Emerging evidence indicates a strong correlation between dendritic spine dysgenesis and neuropathic pain. Because dendritic spines are located on dorsal horn neurons within the spinal cord nociceptive system, dendritic spine remodeling provides a unique opportunity to understand sensory dysfunction after SCI. In this study, we provide support for the postulate that dendritic spine profiles can serve as biomarkers for neuropathic pain. We show that dendritic spine profiles after SCI change to a dysgenic state that is characteristic of neuropathic pain in a Rac1-dependent manner. Suppression of the dysgenic state through inhibition of Rac1 activity is accompanied by attenuation of neuropathic pain. Both dendritic spine dysgenesis and neuropathic pain return when inhibition of Rac1 activity is lifted. These findings suggest the utility of dendritic spines as structural biomarkers for neuropathic pain.
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut; and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut; and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Myriam
authors.initials: M
authors.lastname: Hill
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut; and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut; and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Lubin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut; and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Bangalore
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut; and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut; and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut andrew.tan@yale.edu.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tan
mesh_terms: D000818:Animals; D002408:Catheters, Indwelling; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008839:Microelectrodes; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014110:Touch / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: Rac1; biomarker; dendritic spines; pain; spinal cord injury