Effects of Early Exposure of Isoflurane on Chronic Pain via the Mammalian Target of Rapamycin Signal Pathway

Autor: C. David Mintz, Qun Li, O’Rukevwe Nicole Eregha, Reilley P. Mathena
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Pharmacology
lcsh:Chemistry
Mice
0302 clinical medicine
030202 anesthesiology
Medicine
lcsh:QH301-705.5
Spectroscopy
Cerebral Cortex
Neurons
Isoflurane
TOR Serine-Threonine Kinases
mammalian target of rapamycin (mTOR)
Chronic pain
General Medicine
Immunohistochemistry
3. Good health
Computer Science Applications
medicine.anatomical_structure
Neuropathic pain
Chronic Pain
insular cortex (IC)
medicine.drug
Signal Transduction
Spinal Cord Dorsal Horn
Insular cortex
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Downregulation and upregulation
Animals
Physical and Theoretical Chemistry
Molecular Biology
Anterior cingulate cortex
PI3K/AKT/mTOR pathway
anterior cingulate cortex (ACC)
neuropathic pain
business.industry
Ribosomal Protein S6 Kinases
Organic Chemistry
spinal dorsal horn (SDH)
medicine.disease
anesthesia neurotoxicity
lcsh:Biology (General)
lcsh:QD1-999
Anesthetic
business
030217 neurology & neurosurgery
Biomarkers
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 20, Iss 20, p 5102 (2019)
Volume 20
Issue 20
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
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