Effects of early exposure of isoflurane on chronic pain via the mammalian target of rapamycin signal pathway

Qun Li, Reilley Paige Mathena, O’Rukevwe Nicole Eregha, C. David Mintz

Research output: Contribution to journalArticle

Abstract

Persistent post-surgical pain (PPSP) is a chronic pain condition, often with neuropathic features, that occurs in approximately 20% of children who undergo surgery. The biological basis of PPSP has not been elucidated. Anesthetic drugs can have lasting effects on the developing nervous system, although the clinical impact of this phenomenon is unknown. Here, we used a mouse model to test the hypothesis that early developmental exposure to isoflurane causes cellular and molecular alteration in the pain perception circuitry that causes a predisposition to chronic, neuropathic pain via a pathologic upregulation of the mammalian target of the rapamycin (mTOR) signaling pathway. Mice were exposed to isoflurane at postnatal day 7 and select cohorts were treated with rapamycin, an mTOR pathway inhibitor. Behavioral tests conducted 2 months later showed increased evidence of neuropathic pain, which did not occur in rapamycin-treated animals. Immunohistochemistry showed neuronal activity was chronically increased in the insular cortex, anterior cingulate cortex, and spinal dorsal horn, and activity was attenuated by rapamycin. Immunohistochemistry and western blotting (WB) showed a co-incident chronic, abnormal upregulation in mTOR activity. We conclude that early isoflurane exposure alters the development of pain circuits and has the potential to contribute to PPSP and/or other pain syndromes.

Original languageEnglish (US)
Article number5102
JournalInternational journal of molecular sciences
Volume20
Issue number20
DOIs
StatePublished - Oct 2 2019

    Fingerprint

Keywords

  • Anesthesia neurotoxicity
  • Anterior cingulate cortex (ACC)
  • Insular cortex (IC)
  • Mammalian target of rapamycin (mTOR)
  • Neuropathic pain
  • Spinal dorsal horn (SDH)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this