Effects of Early Exposure of Isoflurane on Chronic Pain via the Mammalian Target of Rapamycin Signal Pathway
| العنوان: | Effects of Early Exposure of Isoflurane on Chronic Pain via the Mammalian Target of Rapamycin Signal Pathway |
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| المؤلفون: | C. David Mintz, Qun Li, O’Rukevwe Nicole Eregha, Reilley P. Mathena |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 20, Iss 20, p 5102 (2019) Volume 20 Issue 20 |
| بيانات النشر: | MDPI, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78ce7241e7d4e97cda09820e8fcde791Test http://europepmc.org/articles/PMC6834214Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....78ce7241e7d4e97cda09820e8fcde791 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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