Phagocytic microglial phenotype induced by glibenclamide improves functional recovery but worsens hyperalgesia after spinal cord injury in adult rats

Elena Redondo-Castro, Joaquim Hernández, Nicole Mahy, Xavier Navarro

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Microglial cell plays a crucial role in the development and establishment of chronic neuropathic pain after spinal cord injuries. As neuropathic pain is refractory to many treatments and some drugs only present partial efficacy, it is essential to study new targets and mechanisms to ameliorate pain signs. For this reason we have used glibenclamide (GB), a blocker of KATP channels that are over expressed in microglia under activation conditions. GB has already been used to trigger the early scavenger activity of microglia, so we administer it to promote a better removal of dead cells and myelin debris and support the microglia neuroprotective phenotype. Our results indicate that a single dose of GB (1 μg) injected after spinal cord injury is sufficient to promote long-lasting functional improvements in locomotion and coordination. Nevertheless, the Randall-Selitto test measurements indicate that these improvements are accompanied by enhanced mechanical hyperalgesia. In vitro results indicate that GB may influence microglial phagocytosis and therefore this action may be at the basis of the results obtained in vivo. Injury to CNS involves an initial microgliosis followed by a more persistent astrogliosis. Ideally, both populations might come back to their resting phenotypes once the lesion is repaired and neuroinflammation is resolved. Spinal cord injuries usually imply an abnormally persistent glial activation, which contributes to the detrimental effects of the secondary phase, such as hyperexcitability and neuropathic pain. Our treatment with GB is aimed to trigger the initial activation of microglia in order to better scavenge all the myelin and cell debris just after the contusion. Indeed, GB promotes a minor infiltration of macrophage and microglia, but with an enhanced phagocytic phenotype. This results as a better functional performance, better tissular preservation, but also a worsening in neuropathic pain signs. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Original languageEnglish
Pages (from-to)3786-3798
JournalEuropean Journal of Neuroscience
Volume38
DOIs
Publication statusPublished - 1 Dec 2013

Keywords

  • Electrophysiology
  • Functional recovery
  • Microglia
  • Neuropathic pain
  • Spinal cord injury

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