title: Loss of central inhibition: implications for behavioral hypersensitivity after contusive spinal cord injury in rats.
abstract: Behavioral hypersensitivity is common following spinal cord injury (SCI), producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8) 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67) and the glycine receptor α3 (GLRA3), notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain.
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, AHC2-481, Miami, FL 33199, USA ; The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Yerko A
authors.initials: YA
authors.lastname: Berrocal
authors.affiliation: The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Vania W
authors.initials: VW
authors.lastname: Almeida
authors.affiliation: The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Rocio
authors.initials: R
authors.lastname: Puentes
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, AHC2-481, Miami, FL 33199, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Knott
authors.affiliation: The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Jaclyn F
authors.initials: JF
authors.lastname: Hechtman
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, AHC2-481, Miami, FL 33199, USA.
authors.forename: Mary
authors.identifier: 0000-0002-8346-4024
authors.initials: M
authors.lastname: Garland
authors.affiliation: The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine, Miami, FL 33136, USA ; The Department of Neurological Surgery, The Neuroscience Program, The Interdisciplinary Stem Cell Institute, The University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Damien D
authors.initials: DD
authors.lastname: Pearse