title: Persistent pain after spinal cord injury is maintained by primary afferent activity.
abstract: Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.8, that is expressed almost exclusively in primary afferent neurons. Selectively knocking down Nav1.8 after SCI suppressed spontaneous activity in dissociated dorsal root ganglion neurons, reversed hypersensitivity of hindlimb withdrawal reflexes, and reduced ongoing pain assessed by a conditioned place preference test. These results show that activity in primary afferent neurons contributes to ongoing SCI pain.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Texas, 77030 Edgar.T.Walters@uth.tmc.edu Qing.Yang@uth.tmc.edu.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Texas, 77030.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Texas, 77030.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Hadden
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Texas, 77030.
authors.forename: Max A
authors.initials: MA
authors.lastname: Odem
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Texas, 77030.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Texas, 77030.
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Crook
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Texas, 77030.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Frost
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Texas, 77030 Edgar.T.Walters@uth.tmc.edu Qing.Yang@uth.tmc.edu.
authors.forename: Edgar T
authors.initials: ET
authors.lastname: Walters
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology*; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013119:Spinal Cord Injuries / Q000150:complications*; D013779:Tetrodotoxin / Q000494:pharmacology; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; D020319:Oligodeoxyribonucleotides, Antisense; C568319:Scn10a protein, rat; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin
keywords: Chronic pain; Nav1.8; dorsal root ganglion; neuropathic pain; nociceptor; spinal contusion
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