Loss of central inhibition: Implications for behavioral hypersensitivity after contusive cpinal cord injury in rats

Yerko A. Berrocal, Vania W. Almeida, Rocio Puentes, Eric P. Knott, Jaclyn F. Hechtman, Mary Garland, Damien D. Pearse

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Article number178278
JournalPain Research and Treatment
Volume2014
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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